ESR1

Summary

ESR1 (estrogen receptor 1, HGNC:3467) is a protein-coding gene on chromosome 6q25.1-q25.2, encoding Estrogen receptor (P03372). Nuclear hormone receptor. In precision oncology, ESR1 D538G confers sensitivity to Elacestrant in Estrogen Receptor-positive Breast Cancer (CIViC Level A); 28 further curated variant–drug associations are listed below.

This gene encodes an estrogen receptor and ligand-activated transcription factor. The canonical protein contains an N-terminal ligand-independent transactivation domain, a central DNA binding domain, a hinge domain, and a C-terminal ligand-dependent transactivation domain. The protein localizes to the nucleus where it may form either a homodimer or a heterodimer with estrogen receptor 2. The protein encoded by this gene regulates the transcription of many estrogen-inducible genes that play a role in growth, metabolism, sexual development, gestation, and other reproductive functions and is expressed in many non-reproductive tissues. The receptor encoded by this gene plays a key role in breast cancer, endometrial cancer, and osteoporosis. This gene is reported to have dozens of transcript variants due to the use of alternate promoters and alternative splicing, however, the full-length nature of many of these variants remain uncertain.

Source: NCBI Gene 2099 — RefSeq curated summary.

At a glance

• Gene–disease (curated): estrogen resistance syndrome (Strong, GenCC)
• GWAS associations: 126 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 230 total — 3 pathogenic
• Regional missense constraint (gnomAD): 1 of 6 regions constrained (≈5% of expected missense variation)
• GTEx eGene: eQTL in 12 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 43
• Drug target: yes — 22 curated mechanism-of-action drugs, 23 via a complex or family; 162 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 15 — Clomiphene Citrate, Dienestrol, Diethylstilbestrol, +12 more
• Approved drugs acting on a complex or family including it: 13 — Bazedoxifene Acetate, Cyclofenil, Diethylstilbestrol Diphosphate, +10 more (Estrogen receptor)
• Precision-oncology evidence (CIViC): 29 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.46 (moderately constrained)
• Transcription factor: yes — 721 downstream targets (CollecTRI)
• MANE Select transcript: NM_000125
• Interaction hub: 7,435 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3467
Approved symbol	ESR1
Name	estrogen receptor 1
Location	6q25.1-q25.2
Locus type	gene with protein product
Status	Approved
Aliases	ER, NR3A1, Era, ER-alpha
Ensembl gene	ENSG00000091831
Ensembl biotype	protein_coding
OMIM	133430
Entrez	2099

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 17 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000206249

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 8, TSL 3: 2, TSL 5: 3

ENST00000206249, ENST00000338799, ENST00000404742, ENST00000406599, ENST00000415488, ENST00000427531, ENST00000440973, ENST00000443427, ENST00000446550, ENST00000456483, ENST00000473497, ENST00000482101, ENST00000488573, ENST00000641399, ENST00000858333, ENST00000858334, ENST00000858335, ENST00000947759, ENST00000988352, ENST00001120066, ENST00001120067, ENST00001120068, ENST00001139102

RefSeq mRNA: 12 — MANE Select: NM_000125 NM_000125, NM_001122740, NM_001122741, NM_001122742, NM_001291230, NM_001291241, NM_001328100, NM_001385568, NM_001385569, NM_001385570, NM_001385571, NM_001385572

CCDS: CCDS5234, CCDS87457

Canonical transcript exons

ENST00000206249 — 8 exons

Exon	Start	End
ENSE00000813753	152011656	152011794
ENSE00001128501	152098732	152103274
ENSE00001877305	151807682	151808364
ENSE00002178920	151944173	151944508
ENSE00003705805	151842597	151842787
ENSE00003721187	151880655	151880771
ENSE00003736522	152094385	152094568
ENSE00003743537	152060991	152061124

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 97.49.

FANTOM5 (CAGE): breadth broad, TPM avg 6.0840 / max 443.8041, expressed in 646 samples.

Highest expression (Bgee): oviduct epithelium, cervix epithelium, mammalian vulva, endometrium, uterine cervix.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ESR1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	1.8e-10	+0.33	6:151950692:A:G
Thyroid	eqtl	2.8e-06	-0.20	6:151676970:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.9e-04	+0.18	6:152107703:C:T
Artery Aorta	eqtl	8.3e-04	+0.26	6:152014101:G:A
Pancreas	eqtl	2.4e-03	+0.24	6:152380861:C:T
Brain Frontal Cortex BA9	eqtl	5.3e-03	-0.27	6:152337081:A:G
Brain Anterior cingulate cortex BA24	eqtl	8.1e-03	+2.55	6:150749054:T:C
Skin Sun Exposed Lower leg	eqtl	2.3e-02	+0.40	6:152453362:C:T
Brain Spinal cord cervical c-1	eqtl	2.3e-02	+0.33	6:151878994:T:C
Colon Sigmoid	eqtl	2.8e-02	+0.16	6:152457463:C:T
Artery Tibial	eqtl	3.5e-02	-0.18	6:151786020:G:A
Ovary	eqtl	3.8e-02	+1.41	6:152589660:A:C

FANTOM5 promoters

showing 10 of 18 alternative TSS:

Promoter ID	TPM avg	Samples expressed
70636	1.6303	159
70616	1.2472	480
70627	0.5161	166
70628	0.4835	172
70617	0.4010	158
70635	0.3671	126
70615	0.2836	150
70638	0.2349	110
70629	0.2308	99
70631	0.2192	96

Top tissues by expression

showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	97.49	gold quality
cervix epithelium	UBERON:0004801	96.89	gold quality
mammalian vulva	UBERON:0000997	96.85	gold quality
endometrium	UBERON:0001295	96.64	gold quality
uterine cervix	UBERON:0000002	96.04	gold quality
cervix squamous epithelium	UBERON:0006922	95.98	gold quality
fallopian tube	UBERON:0003889	95.94	gold quality
endocervix	UBERON:0000458	95.16	gold quality
right uterine tube	UBERON:0001302	94.72	gold quality
uterus	UBERON:0000995	94.53	gold quality
ectocervix	UBERON:0012249	94.34	gold quality
epithelium of mammary gland	UBERON:0003244	94.10	gold quality
mammary duct	UBERON:0001765	93.85	gold quality
body of uterus	UBERON:0009853	93.61	gold quality
vagina	UBERON:0000996	93.35	gold quality
caput epididymis	UBERON:0004358	92.43	gold quality
germinal epithelium of ovary	UBERON:0001304	91.68	gold quality
calcaneal tendon	UBERON:0003701	91.13	gold quality
urethra	UBERON:0000057	90.87	gold quality
myometrium	UBERON:0001296	90.85	gold quality
tibia	UBERON:0000979	90.56	gold quality
mammary gland	UBERON:0001911	89.63	gold quality
thoracic mammary gland	UBERON:0005200	89.62	gold quality
left uterine tube	UBERON:0001303	89.21	gold quality
adult organism	UBERON:0007023	88.52	gold quality
female reproductive system	UBERON:0000474	88.11	gold quality
nipple	UBERON:0002030	86.20	gold quality
tendon	UBERON:0000043	85.42	gold quality
decidua	UBERON:0002450	83.72	gold quality
right lobe of liver	UBERON:0001114	83.44	gold quality
liver	UBERON:0002107	83.43	gold quality
seminal vesicle	UBERON:0000998	83.12	gold quality
sperm	CL:0000019	82.93	gold quality
smooth muscle tissue	UBERON:0001135	82.21	gold quality
male germ cell	CL:0000015	81.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.67	gold quality
blood vessel layer	UBERON:0004797	80.49	gold quality
skin of hip	UBERON:0001554	80.14	gold quality
tendon of biceps brachii	UBERON:0008188	79.53	silver quality
ovary	UBERON:0000992	78.89	gold quality
left ovary	UBERON:0002119	77.56	gold quality
saphenous vein	UBERON:0007318	77.44	gold quality
deltoid	UBERON:0001476	76.31	silver quality
pituitary gland	UBERON:0000007	75.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.62	gold quality
islet of Langerhans	UBERON:0000006	75.19	gold quality
right ovary	UBERON:0002118	75.05	gold quality
prostate gland	UBERON:0002367	74.84	gold quality
synovial joint	UBERON:0002217	74.46	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.31	gold quality
parietal pleura	UBERON:0002400	73.29	gold quality
penis	UBERON:0000989	73.08	gold quality
muscle tissue	UBERON:0002385	72.88	gold quality
tibialis anterior	UBERON:0001385	72.81	silver quality
pleura	UBERON:0000977	72.79	gold quality
layer of synovial tissue	UBERON:0007616	72.53	gold quality
adenohypophysis	UBERON:0002196	72.27	gold quality
bone marrow cell	CL:0002092	72.23	gold quality
tibial artery	UBERON:0007610	72.16	gold quality
popliteal artery	UBERON:0002250	72.13	gold quality
epithelial cell of pancreas	CL:0000083	71.98	silver quality
skeletal muscle tissue	UBERON:0001134	71.97	gold quality
connective tissue	UBERON:0002384	71.97	gold quality
endothelial cell	CL:0000115	71.92	silver quality
endometrium epithelium	UBERON:0004811	71.92	silver quality
adipose tissue	UBERON:0001013	71.90	gold quality
aorta	UBERON:0000947	71.40	gold quality
right coronary artery	UBERON:0001625	71.30	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	71.29	silver quality
diaphragm	UBERON:0001103	71.22	gold quality
cauda epididymis	UBERON:0004360	71.12	gold quality
vastus lateralis	UBERON:0001379	71.10	silver quality
quadriceps femoris	UBERON:0001377	71.02	silver quality
muscle organ	UBERON:0001630	71.00	gold quality
skeletal muscle organ	UBERON:0014892	71.00	gold quality
muscle of leg	UBERON:0001383	70.74	gold quality
ascending aorta	UBERON:0001496	70.58	gold quality
thoracic aorta	UBERON:0001515	70.45	gold quality
urinary bladder	UBERON:0001255	70.44	gold quality
visceral pleura	UBERON:0002401	70.42	gold quality
subcutaneous adipose tissue	UBERON:0002190	70.38	gold quality
periodontal ligament	UBERON:0008266	70.30	gold quality
coronary artery	UBERON:0001621	70.06	gold quality
biceps brachii	UBERON:0001507	70.04	gold quality
left coronary artery	UBERON:0001626	70.04	gold quality
descending thoracic aorta	UBERON:0002345	69.69	gold quality
triceps brachii	UBERON:0001509	69.59	gold quality
gluteal muscle	UBERON:0002000	69.48	gold quality
corpus epididymis	UBERON:0004359	69.48	gold quality
sural nerve	UBERON:0015488	69.43	gold quality
adipose tissue of abdominal region	UBERON:0007808	68.76	gold quality
gastrocnemius	UBERON:0001388	68.68	gold quality
olfactory bulb	UBERON:0002264	68.46	gold quality
colonic epithelium	UBERON:0000397	68.42	silver quality
lymph node	UBERON:0000029	68.37	gold quality
peritoneum	UBERON:0002358	67.95	gold quality
omental fat pad	UBERON:0010414	67.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.82	gold quality
thyroid gland	UBERON:0002046	67.73	gold quality
trachea	UBERON:0003126	67.47	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	1321.93
E-MTAB-10287	yes	45.00
E-CURD-119	yes	12.34
E-ANND-3	yes	6.53

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Endometrium 1	tissue	103.7	high
Cervix	tissue	78.7	high
Fallopian tube	tissue	61.1	medium
Smooth muscle	tissue	47.1	low
Vagina	tissue	45.7	high
Breast	tissue	27.4	medium
Liver	tissue	15.8	not detected
Choroid plexus	tissue	9.7
Seminal vesicle	tissue	9.3	not detected
Ovary	tissue	8.6	not detected
Hypothalamus	tissue	6.7
Pituitary gland	tissue	6.3
Prostate	tissue	5.7	not detected
Amygdala	tissue	5.5
Skeletal muscle	tissue	5.4	not detected
Nucleus accumbens	tissue	4.5
Adipose tissue	tissue	4.0	not detected
Septum	tissue	3.9
Cerebellum	tissue	3.6	not detected
Periaqueductal gray	tissue	3.5
Basal ganglia	tissue	3.4	not detected
Retina	tissue	3.2
Thyroid gland	tissue	3.2	not detected
Hippocampus	tissue	3.2	not detected
Postcentral gyrus	tissue	3.1
Pons	tissue	2.9
Hippocampal formation	tissue	2.9
Putamen	tissue	2.6
Kidney	tissue	2.6	not detected
Ventral forebrain	tissue	2.6
Locus coeruleus	tissue	2.5
Tongue	tissue	2.4
Substantia nigra	tissue	2.4
Cerebral cortex	tissue	2.3	not detected
Motor cortex	tissue	2.3
Medulla oblongata	tissue	2.1
Tonsil	tissue	2.1	not detected
Entorhinal cortex	tissue	2.1
Temporal cortex	tissue	2.1
Insular cortex	tissue	2.1
Prefrontal cortex	tissue	2.0
Midbrain	tissue	2.0
Thalamus	tissue	2.0
Superior colliculi	tissue	1.9
Retrosplenial and cingulate cortex	tissue	1.9
Retrosplenial cortex	tissue	1.9
Testis	tissue	1.8	not detected
Somatosensory cortex	tissue	1.8
Occipital cortex	tissue	1.8
Lung	tissue	1.7	not detected
Spinal cord	tissue	1.7
Adrenal gland	tissue	1.7	not detected
Spleen	tissue	1.6	not detected
Lymph node	tissue	1.5	not detected
Urinary bladder	tissue	1.3	not detected
Frontal cortex	tissue	1.2
Heart muscle	tissue	1.1	not detected
Epididymis	tissue	1.1	not detected
Gallbladder	tissue	1.1	not detected
Corpus callosum	tissue	1.1

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Arcuate nucleus (17.5), Ventromedial nucleus (15.8), Corticomedial amygdala (9.2), Vermis (8.9), Flocculonodular lobe (8.8).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

showing 30 of 721 targets:

Target	Regulation
AATF
ABCB1
ABCB10
ABCB11	Unknown
ABCC2	Unknown
ABCC3	Unknown
ABCG2	Unknown
ABL1
ACE2	Unknown
ACHE
ACKR3
ACP3	Unknown
ACSBG1
ADA
ADAM17
ADAM2
ADCYAP1
ADIPOQ
ADIPOR1
ADORA1	Unknown
AFMID
AGL
AGO1
AGO2
AGO3
AGO4
AGTR2	Unknown
AHR	Unknown
AICDA	Activation
AIP

JASPAR motifs

Motif	Name	Family
MA0112.1	ESR1	Steroid hormone receptors (NR3)
MA0112.2	ESR1	Steroid hormone receptors (NR3)
MA0112.3	ESR1	Steroid hormone receptors (NR3)
MA0112.4	ESR1	Steroid hormone receptors (NR3)

JASPAR matrix evidence (PMIDs): PMID:15563547, PMID:19339991

Upstream regulators (CollecTRI, top): AHR, AIP, AP1, AR, ARID5A, ARNT, ATF6, BARD1, BARX2, BRCA1, CEBPD, CREB1, DBP, DNMT1, DNMT3A, DNMT3B, E2F4, ESR1, ESR2, ESRRA, FLI1, FOS, FOSL1, FOXA1, FOXC1, FOXE1, FOXM1, FOXN1, FOXO3, FOXP1, GATA1, GATA3, HDAC1, HDAC7, HDAC9, HESX1, HIF1A, HOXA10, HOXB13, HTATIP2

miRNA regulators (miRDB)

Targeting ESR1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 269 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593

Functional genomics

gnomAD constraint: pLI 0.998, LOEUF 0.456, missense Z 2.46 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000206249 splits into 6 regions with different missense tolerance; 1 is missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
6:151,807,913–151,842,688	251 / 246.1	1.02	no
6:151,842,689–151,842,780	8 / 36.9	0.22	yes (p 1.9e-06)
6:151,842,781–151,880,762	25 / 53.0	0.47	no
6:151,880,763–151,944,362	88 / 88.3	1.00	no
6:151,944,363–152,098,820	141 / 289.3	0.49	no
6:152,098,821–152,098,963	71 / 66.1	1.07	no

Literature-anchored findings (GeneRIF, showing 40)

• The ligand-binding domain of estrogen receptor alpha has been expressed, purified, and crystallized to yield high amounts of soluble protein, in order to solve the structure in its native form without renaturation or modification steps. (PMID:11437591)
• ERa but not ERbeta is present in human preadipocytes (PMID:11720251)
• Association of a T262C transition in exon 1 of estrogen-receptor-alpha gene with skeletal responsiveness to estrogen in post-menopausal women. (PMID:11765043)
• To determine whether receptor-induced changes in DNA structure are related to transactivation, we compared the abilities of ER alpha and ER beta to activate transcription and induce distortion and bending in DNA. (PMID:11773069)
• Estrogen receptors are found in brain areas involved in regulation of food intake. The anorexic effects of estrogen are accentuated by stress, thus that variation in the estrogen receptors may contribute to the genetic susceptibility to AN in females. (PMID:11803451)
• Reduction of coactivator expression by antisense oligodeoxynucleotides inhibits ERalpha transcriptional activity and MCF-7 proliferation (PMID:11818499)
• mutations targeted to predicted helix in the extreme carboxyl-terminal region alter its response to estradiol and 4-hydroxytamoxifen (PMID:11823467)
• expression of estrogen receptor alpha and estrogen receptor beta were studied in leiomyomas and homologous myometrium from women in the proliferative phase of the menstrual cycle and from women treated with a gonadotropin-releasing hormone analogue (PMID:11826769)
• Estrogen receptors play a role in the activation of amino acid transport system A by estrogen. (PMID:11836633)
• patients that progressed to breast cancer showed significantly higher ER-alpha expression in their HUT (hyperplasia of usual type)foci compared with controls (PMID:11839580)
• There was strong linkage disequilibrium between the three loci and a significant sex difference was observed in allele (for (TA)(n), PvuII) and genotype (for XbaI) frequencies. (PMID:11857578)
• Results indicate a weak and transient activation of estrogen receptors by estradiol stimulation that may be enhanced by growth factors. (PMID:11867270)
• RTA, a negative coregulator for ERalpha was isolated (PMID:11875103)
• Coronary artery wall atherosclerosis in relation to the estrogen receptor 1 gene polymorphism: an autopsy study; the ESR1 gene is a potential candidate behind the pathogenesis of acute coronary events (PMID:11894143)
• role in blood pressure (PMID:11903314)
• Mutations of tyrosine 537 in the human estrogen receptor-alpha selectively alter the receptor’s affinity for estradiol and the kinetics of the interaction (PMID:11914066)
• these results show that although estrogen can up-regulate endogenous PR gene expression in osteoblasts via both ER isoforms, ER-alpha is the predominant inducer (PMID:11918216)
• Postmenopausal women with coronary disease who have the ER-alpha IVS1-401 C/C genotype, or several other closely related genotypes, have an augmented response of HDL cholesterol to hormone-replacement therapy. (PMID:11919305)
• Results show that DNA-102 produced a 36-fold increase in the level of total ER alpha mRNA and a 12-fold increase in the level of mRNA for the F isoform transcribed from the upstream F promoter, and induced a more differentiated osteoblastic phenotype. (PMID:11922631)
• the extent of AF-2-dependent cofactor recruitment by ERalpha or ERbeta is affected both by ER ligands and estrogen-responsive element sequences (PMID:11923465)
• Association of polymorphisms of the oestrogen receptor alpha gene with the age of menarche (PMID:11925413)
• Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor alpha (PMID:11937504)
• crystal structures of the ER alpha ligand binding domain (LBD) bound to both THC and a fragment of the transcriptional coactivator GRIP1, and the ER beta LBD bound to THC (PMID:11953755)
• MAP kinase mediates growth factor-induced nuclear translocation of estrogen receptor alpha. (PMID:11959092)
• Identification of ten exon deleted ERbeta mRNAs in human ovary, breast, uterus and bone tissues: alternate splicing pattern of estrogen receptor beta mRNA is distinct from that of estrogen receptor alpha. (PMID:11959119)
• possesses a novel large-scale chromatin unfolding activity when tethered or recruited to DNA (PMID:11971975)
• demonstrated that ERalpha but not ERbeta directly interacts with calmodulin (PMID:11981030)
• effect on cyclin D1 expression (PMID:11986316)
• genetic variants in panic disorder (PMID:11992565)
• in addition to the alternative cis-splicing, the hER alpha gene is also subject to natural trans-splicing (PMID:12011094)
• estrogen via estrogen receptor 1 directly modulates differentiation of bipotential stromal cells into the osteoblast and adipocyte lineages, causing a lineage shift toward the osteoblast (PMID:12021200)
• contribution of genetic polymorphism of oestrogen and androgen receptor (AR) genes in male infertility (PMID:12031042)
• ADA3-containing complexes associate with estrogen receptor alpha (PMID:12034840)
• PRMT2 is a novel ERalpha coactivator. (PMID:12039952)
• review of connections and regulation of the human estrogen receptor alpha (PMID:12040178)
• tentative findings provide evidence that genetic variation in ESR1 may modify coronary reactivity and LDL oxidation and reflect differences in the early pathogenesis of coronary dysfunction in these healthy young men (PMID:12059984)
• Expression of c-erbB-2 in node negative breast cancer does not correlate with estrogen receptor status, predictors of hormone responsiveness, or PCNA expression. (PMID:12088102)
• The constitutively activated MAP kinase cascade in endometrial cancer cells enhances ERalpha transcriptional activity via the AF1 domain. This activation pathway may be involved in the stimulatory effect of tamoxifen on endometrial cancer. (PMID:12088871)
• Structural regions (BOX-1 & -2)required for the ability of ERalpha to induce transcription synergistically from tandem ERE sequences are also critical for the interaction of the receptor with the co-regulatory proteins. (PMID:12088878)
• Formation of an hER alpha-COUP-TFI complex enhances hER alpha AF-1 through Ser118 phosphorylation by MAPK. (PMID:12093745)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	esr1	ENSDARG00000004111
mus_musculus	Esr1	ENSMUSG00000019768
rattus_norvegicus	Esr1	ENSRNOG00000019358
drosophila_melanogaster	ERR	FBGN0035849

Paralogs (8): PGR (ENSG00000082175), NR3C1 (ENSG00000113580), ESRRB (ENSG00000119715), ESR2 (ENSG00000140009), NR3C2 (ENSG00000151623), AR (ENSG00000169083), ESRRA (ENSG00000173153), ESRRG (ENSG00000196482)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1352467) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 235 distinct phenotype terms.

Mouse phenotype (MP)	Records
absent corpus luteum	12
female infertility	12
abnormal ovary morphology	8
abnormal response/metabolism to endogenous compounds	8
increased circulating estradiol level	8
ovarian follicular cyst	8
abnormal mammary gland development	7
increased circulating luteinizing hormone level	7
increased circulating testosterone level	7
increased body weight	6
ovary hemorrhage	6
uterus hypoplasia	5
obese	4
male infertility	4
abnormal estrous cycle	4
small uterus	4
oligozoospermia	4
decreased uterus weight	4
abnormal branching of the mammary ductal tree	3
abnormal uterus morphology	3
seminiferous tubule degeneration	3
abnormal osteoclast physiology	3
decreased circulating luteinizing hormone level	3
short femur	3
decreased circulating insulin-like growth factor I level	3

+210 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RAM2	99.8%	Diamond
Saimiri boliviensis boliviensis	O13186	99.7%	Diamond
Saimiri sciureus	O46567	99.7%	Diamond
Cricetulus griseus	P57797	99.6%	Diamond
Pan troglodytes	A7X8B3	99.5%	Diamond
Pan paniscus	A7X8B5	99.5%	Diamond
Aotus nancymaae	P79686	99.5%	Diamond
Saguinus oedipus	P79269	99.4%	Diamond
Callithrix jacchus	Q6XLJ0	99.4%	Diamond
Canis lupus familiaris	Q6QMY5	99.3%	Diamond
Macaca mulatta	O18924	99.2%	Diamond
Gorilla gorilla gorilla	A7X8B7	99.1%	Diamond
Bos taurus	P49884	99.1%	Diamond
Ovis aries	P49885	99.1%	Diamond
Macaca sylvanus	A7X8C4	98.3%	Diamond
Papio anubis	A7X8C7	98.3%	Diamond
Sus scrofa	Q29040	98.3%	Diamond
Felis catus	Q53AD2	98.3%	Diamond
Oryctolagus cuniculus	O19052	98.1%	Diamond
Coturnix japonica	O93511	98.1%	Diamond
Gallus gallus	Q9PTU5	98.1%	Diamond
Colobus guereza	A7X8D2	98.0%	Diamond
Trachypithecus obscurus	A7X8D4	98.0%	Diamond
Chlorocebus aethiops	A7X8C9	97.5%	Diamond
Mesocricetus auratus	Q9QZJ5	97.5%	Diamond
Pongo pygmaeus	A7X8B9	97.4%	Diamond
Hylobates lar	A7X8C2	97.1%	Diamond
Sapajus apella	A7XW16	97.1%	Diamond
Pithecia irrorata	A7XW20	97.1%	Diamond
Ateles paniscus	A7XW25	97.1%	Diamond
Taeniopygia guttata	Q91250	96.9%	Diamond
Pagrus major	O42132	96.7%	Diamond
Sparus aurata	Q9PVZ9	96.7%	Diamond
Equus caballus	Q9TV98	96.7%	Diamond
Oncorhynchus mykiss	P16058	95.5%	Diamond
Salmo salar	P50242	95.5%	Diamond
Tupaia belangeri	Q29131	93.5%	Diamond
Notamacropus eugenii	P79373	93.3%	Diamond
Aspidoscelis uniparens	Q91424	92.5%	Diamond
Ictalurus punctatus	Q9YHZ7	92.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SYNE1-AS2	ncRNA	124901437
SYNE1	protein-coding	23345
CCDC170	protein-coding	80129
SYNE1-AS1	ncRNA	100505475
MYCT1	protein-coding	80177
DCPH1	protein-coding	79624

Protein

Protein identifiers

Estrogen receptor — P03372 (reviewed: P03372)

Alternative names: ER-alpha, Estradiol receptor, Nuclear receptor subfamily 3 group A member 1

All UniProt accessions (8): B0QYW7, P03372, G4XH65, H0Y4W6, Q5T5H8, Q9H2M1, Q9H2M2, Q9UE35

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2). Involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor. Binds to ERE and inhibits isoform 1.

Subunit / interactions. Binds DNA as a homodimer. Can form a heterodimer with ESR2. Interacts with FOXC2, MAP1S, SLC30A9, UBE1C and NCOA3 coactivator. Interacts with PELP1, the interaction is enhanced by 17-beta-estradiol, the interaction increases ESR1 transcriptional activity. Interacts with EP300; the interaction is estrogen-dependent and enhanced by CITED1. Interacts with CITED1; the interaction is estrogen-dependent. Interacts with NCOA5 and NCOA6 coactivators. Interacts with NCOA7; the interaction is a ligand-inducible. Interacts with PHB2, and UBE1C. Interacts with AKAP13. Interacts with CUEDC2. Interacts with KDM5A. Interacts with SMARD1. Interacts with HEXIM1. Interacts with PBXIP1. Interaction with MUC1 is stimulated by 7 beta-estradiol (E2) and enhances ESR1-mediated transcription. Interacts with DNTTIP2, FAM120B and UIMC1. Interacts with isoform 4 of TXNRD1. Interacts with KMT2D/MLL2. Interacts with ATAD2 and this interaction is enhanced by estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG. Interaction with SH2D4A blocks binding to PLCG and inhibits estrogen-induced cell proliferation. Interacts with DYNLL1. Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems to enhance the transcription of target genes. Interacts with NR2C1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. Interacts with DNAAF4. Interacts with PRMT2. Interacts with RBFOX2. Interacts with STK3/MST2 only in the presence of SAV1 and vice-versa. Interacts with NCOA2; NCOA2 can interact with ESR1 AF-1 and AF-2 domains simultaneously and mediate their transcriptional synergy. Interacts with DDX5. Interacts with NCOA1; the interaction seems to require a self-association of N-terminal and C-terminal regions. Interacts with ZNF366, DDX17, NFKB1, RELA, SP1 and SP3. Interacts with NRIP1. Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts with CLOCK and the interaction is stimulated by estrogen. Interacts with BCAS3. Interacts with TRIP4 (ufmylated); estrogen dependent. Interacts with LMTK3; the interaction phosphorylates ESR1 (in vitro) and protects it against proteasomal degradation. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with ZFHX3. Interacts with SFR1 in a ligand-dependent and -independent manner. Interacts with DCAF13, LATS1 and DCAF1; regulates ESR1 ubiquitination and ubiquitin-mediated proteasomal degradation. Interacts (via DNA-binding domain) with POU4F2 (C-terminus); this interaction increases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner. Interacts with ESRRB isoform 1. Interacts with UBE3A and WBP2. Interacts with GTF2B. Interacts with RBM39. In the absence of hormonal ligand, interacts with TACC1. Interacts with PI3KR1 or PI3KR2 and PTK2/FAK1. Interacts with SRC. Interacts with BAG1; the interaction is promoted in the absence of estradiol (17-beta-estradiol/E2). Interacts with and ubiquitinated by STUB1; the interaction is promoted in the absence of estradiol (17-beta-estradiol/E2). Interacts with NEDD8. Probably homodimerizes or heterodimerizes with isoform 1 and ESR2.

Subcellular location. Nucleus. Cytoplasm. Cell membrane Nucleus. Cell membrane. Golgi apparatus.

Tissue specificity. Widely expressed. Not expressed in the pituitary gland. Widely expressed, however not expressed in the pituitary gland.

Post-translational modifications. Phosphorylated by cyclin A/CDK2. Self-association induces phosphorylation. Dephosphorylation at Ser-118 by PPP5C inhibits its transactivation activity. Phosphorylated by LMTK3 in vitro. Glycosylated; contains N-acetylglucosamine, probably O-linked. Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1 proteasomal degradation. Deubiquitinated by OTUB1. Ubiquitinated by STUB1/CHIP; in the CA1 hippocampal region following loss of endogenous circulating estradiol (17-beta-estradiol/E2). Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound ESR1 when it is not associated with coactivators (NCOAs). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation. Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization. Demethylated by JMJD6 at Arg-260. Palmitoylated (isoform 3). Not biotinylated (isoform 3). Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation, but not for signaling mediated by the nuclear hormone receptor.

Disease relevance. Estrogen resistance (ESTRR) [MIM:615363] A disorder characterized by partial or complete resistance to estrogens, in the presence of elevated estrogen serum levels. Clinical features include absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, reduced bone mineral density, osteoporosis, continued growth into adulthood and very tall adult stature. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The modulating domain, also known as A/B or AF-1 domain has a ligand-independent transactivation function. The C-terminus contains a ligand-dependent transactivation domain, also known as E/F or AF-2 domain which overlaps with the ligand binding domain. AF-1 and AF-2 activate transcription independently and synergistically and act in a promoter- and cell-specific manner. AF-1 seems to provide the major transactivation function in differentiated cells.

Polymorphism. Genetic variations in ESR1 are correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disruption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.

Miscellaneous. Selective estrogen receptor modulators (SERMs), such as tamoxifen, raloxifene, toremifene, lasofoxifene, clomifene, femarelle and ormeloxifene, have tissue selective agonistic and antagonistic effects on the estrogen receptor (ER). They interfere with the ER association with coactivators or corepressors, mainly involving the AF-2 domain. Produced by alternative promoter usage. Produced by alternative splicing of isoform 3.

Similarity. Belongs to the nuclear hormone receptor family. NR3 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P03372-1	1, Long, hER-alpha66, ER66	yes
P03372-2	2, Short
P03372-3	3, hER-alpha46, ER46
P03372-4	4, hER-alpha36, ER36

RefSeq proteins (12): NP_000116, NP_001116212, NP_001116213, NP_001116214, NP_001278159, NP_001278170, NP_001315029, NP_001372497, NP_001372498, NP_001372499, NP_001372500, NP_001372501 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001292	Estr_rcpt	Family
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR024178	Est_rcpt/est-rel_rcp	Family
IPR024736	Oestrogen-typ_rcpt_final_C_dom	Domain
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR046944	Estr_rcpt_N	Domain
IPR050200	Nuclear_hormone_rcpt_NR3	Family

Pfam: PF00104, PF00105, PF02159, PF12743

UniProt features (88 total): helix 21, mutagenesis site 12, region of interest 11, strand 9, sequence variant 8, modified residue 6, turn 5, binding site 3, splice variant 3, compositionally biased region 2, zinc finger region 2, chain 1, domain 1, DNA-binding region 1, lipid moiety-binding region 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

showing 30 of 492 structures by resolution:

PDB	Title	Method	Resolution (Å)
7BAA	Cys-42-tethered stabilizer 12 of 14-3-3(sigma)/ERa PPI	X-RAY DIFFRACTION	1.1
8BZC	co-soaked stabilizers for ERa - 14-3-3 interaction (884_AZ244)	X-RAY DIFFRACTION	1.1
8BZW	Co-soaked stabilizers for ERa - 14-3-3 interaction (844_AZ210)	X-RAY DIFFRACTION	1.1
8C04	Co-soaked stabilizers for ERa - 14-3-3 interaction (884_AZ354)	X-RAY DIFFRACTION	1.1
7B9R	Cys-45-tethered stabilizer 4 of 14-3-3(sigma)/ERa PPI	X-RAY DIFFRACTION	1.15
7B9T	Cys-45-tethered stabilizer 5 of 14-3-3(sigma)/ERa PPI	X-RAY DIFFRACTION	1.15
7NFW	Human 14-3-3 sigma in complex with human Estrogen Receptor alpha peptide	X-RAY DIFFRACTION	1.19
6HMU	Ternary complex of Estrogen Receptor alpha peptide and 14-3-3 sigma C45 mutant bound to …	X-RAY DIFFRACTION	1.2
7BA8	Cys-42-tethered stabilizer 10 of 14-3-3(sigma)/ERa PPI	X-RAY DIFFRACTION	1.2
8APS	Small molecular stabilizer for ERalpha and 14-3-3 (1083744)	X-RAY DIFFRACTION	1.2
8BX3	fragment-linked stabilizer for ERa - 14-3-3 interaction (1074372)	X-RAY DIFFRACTION	1.2
8BXI	fragment-linked stabilizer for ERa - 14-3-3 interaction (1074361)	X-RAY DIFFRACTION	1.2
8BYO	fragment-linked stabilizer for ERa - 14-3-3 interaction (1074361)	X-RAY DIFFRACTION	1.2
8BZ0	single soak stabilizer for ERa - 14-3-3 interaction (AZ275)	X-RAY DIFFRACTION	1.2
8BZA	single soak stabilizer for ERa - 14-3-3 interaction (AZ555)	X-RAY DIFFRACTION	1.25
7BAB	Cys-42-tethered stabilizer 13 of 14-3-3(sigma)/ERa PPI	X-RAY DIFFRACTION	1.3
8BZ9	single soak stabilizer for ERa - 14-3-3 interaction (AZ354)	X-RAY DIFFRACTION	1.3
9I6S	14-3-3sigma binding to the ERa peptide and compound 28	X-RAY DIFFRACTION	1.3
9I6T	14-3-3sigma binding to the ERa peptide and compound 32	X-RAY DIFFRACTION	1.3
9I6U	14-3-3sigma binding to the ERa peptide and compound 33	X-RAY DIFFRACTION	1.3
9I6V	14-3-3sigma binding to the ERa peptide and compound 40	X-RAY DIFFRACTION	1.3
9I6W	14-3-3sigma binding to the ERa peptide and compound 41	X-RAY DIFFRACTION	1.3
9I6X	14-3-3sigma binding to the ERa peptide and compound 42	X-RAY DIFFRACTION	1.3
7NFB	ER-PRS*(+) (Y537S) in complex with genistein and SRC-2 coactivator peptide	X-RAY DIFFRACTION	1.33
8ARR	Small molecular stabilizer for ERalpha and 14-3-3 (1076394)	X-RAY DIFFRACTION	1.35
9I71	14-3-3sigma binding to the ERa peptide and compound 19	X-RAY DIFFRACTION	1.35
9I72	14-3-3sigma binding to the ERa peptide and compound 10	X-RAY DIFFRACTION	1.35
8AFN	Small molecule stabilizer (compound 1) for ERalpha and 14-3-3	X-RAY DIFFRACTION	1.36
7BA3	Cys-42-tethered stabilizer 6 of 14-3-3(sigma)/ERa PPI	X-RAY DIFFRACTION	1.4
7BA6	Cys-42-tethered stabilizer 8 of 14-3-3(sigma)/ERa PPI	X-RAY DIFFRACTION	1.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P03372-F1	67.14	0.45

Human Protein Atlas

Protein class: Nuclear receptors, Predicted intracellular proteins, Transcription factors, Zinc-coordinating DNA-binding domains, Cancer-related genes, Candidate cancer biomarkers, Mutational cancer driver genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3)

Position	Role
353	17beta-estradiol
394	17beta-estradiol
524	17beta-estradiol

Post-translational modifications (7)

Type	Positions
Phosphoserine	104, 106, 118, 167
Asymmetric dimethylarginine	260
Phosphotyrosine	537
S-palmitoyl cysteine	447

Glycosylation sites (1)

Type	Positions
O-linked (glcnac) serine	10

Mutagenesis-validated functional residues (12)

Position	Phenotype
39	impairs af-1 transactivation.
43	impairs af-1 transactivation.
104	loss of cyclin a-dependent induction of transcriptional activation.
106	loss of cyclin a-dependent induction of transcriptional activation.
118	decreases phosphorylation and transactivation activity. abolishes af-1 transactivation. insensitive to ppp5c inhibition of transactivation …
118	enhances transactivation activity. insensitive to ppp5c inhibition of transactivation activity.
260	loss of methylation.
364	has higher transcriptional activity in the absence of wild type er. inhibits transcriptional activity when coexpressed with the wild type …
386	loss of transmembrane localization, no effect on peripheral membrane localization. impairs activation of estrogen-induced activation of …
447	loss of hormone binding capacity and temperature-sensitive loss in dna-binding.
537	reduces pelp1-mediated activation of transcriptional activity.
539	abolishes interaction with ncoa1, ncoa2 and ncoa3.

Function

Pathways and Gene Ontology

Reactome pathways

16 curated (TAS) of 39; 4 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

39 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-9927426	Developmental Lineage of Mammary Gland Alveolar Cells	curated
R-HSA-9927418	Developmental Lineage of Mammary Gland Luminal Epithelial Cells	curated
R-HSA-8939211	ESR-mediated signaling	curated
R-HSA-9018519	Estrogen-dependent gene expression	curated
R-HSA-9009391	Extra-nuclear estrogen signaling	curated
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)	curated
R-HSA-383280	Nuclear Receptor transcription pathway	curated
R-HSA-1251985	Nuclear signaling by ERBB4	curated
R-HSA-5689896	Ovarian tumor domain proteases	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-8931987	RUNX1 regulates estrogen receptor mediated transcription	curated
R-HSA-8939256	RUNX1 regulates transcription of genes involved in WNT signaling	curated
R-HSA-4090294	SUMOylation of intracellular receptors	curated
R-HSA-8866910	TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-2219528	PI3K/AKT Signaling in Cancer ⚕	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-5688426	Deubiquitination	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-199418	Negative regulation of the PI3K/AKT network	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-8939902	Regulation of RUNX2 expression and activity	electronic
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	—
R-HSA-2990846	SUMOylation	—
R-HSA-162582	Signal Transduction	—
R-HSA-1236394	Signaling by ERBB4	—
R-HSA-9006931	Signaling by Nuclear Receptors	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-8878171	Transcriptional regulation by RUNX1	—
R-HSA-8878166	Transcriptional regulation by RUNX2	—
R-HSA-8864260	Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	—

MSigDB gene sets: 693 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GCACCTT_MIR18A_MIR18B, ELVIDGE_HYPOXIA_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, MORF_FLT1, WANG_CLIM2_TARGETS_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_GLAND_MORPHOGENESIS, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, PID_TELOMERASE_PATHWAY, GOBP_RESPONSE_TO_ESTRADIOL, MORF_MSH3, GOBP_PROSTATE_GLAND_MORPHOGENESIS, GOBP_INFLAMMATORY_RESPONSE

GO Biological Process (28): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), signal transduction (GO:0007165), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), negative regulation of gene expression (GO:0010629), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518), estrogen receptor signaling pathway (GO:0030520), response to estradiol (GO:0032355), negative regulation of smooth muscle cell apoptotic process (GO:0034392), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), steroid hormone receptor signaling pathway (GO:0043401), response to estrogen (GO:0043627), positive regulation of nitric oxide biosynthetic process (GO:0045429), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), stem cell differentiation (GO:0048863), positive regulation of nitric-oxide synthase activity (GO:0051000), RNA polymerase II preinitiation complex assembly (GO:0051123), protein localization to chromatin (GO:0071168), cellular response to estrogen stimulus (GO:0071391), cellular response to estradiol stimulus (GO:0071392), negative regulation of miRNA transcription (GO:1902894), regulation of gene expression (GO:0010468), intracellular receptor signaling pathway (GO:0030522), cellular response to oxygen-containing compound (GO:1901701)

GO Molecular Function (31): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), TFIIB-class transcription factor binding (GO:0001093), transcription coregulator binding (GO:0001221), transcription corepressor binding (GO:0001222), transcription coactivator binding (GO:0001223), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), nuclear receptor activity (GO:0004879), steroid binding (GO:0005496), calmodulin binding (GO:0005516), beta-catenin binding (GO:0008013), zinc ion binding (GO:0008270), TBP-class protein binding (GO:0017025), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), nitric-oxide synthase regulator activity (GO:0030235), nuclear estrogen receptor activity (GO:0030284), nuclear estrogen receptor binding (GO:0030331), estrogen response element binding (GO:0034056), identical protein binding (GO:0042802), ATPase binding (GO:0051117), 14-3-3 protein binding (GO:0071889), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), nuclear steroid receptor activity (GO:0003707), protein binding (GO:0005515), lipid binding (GO:0008289), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (10): chromatin (GO:0000785), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), protein-containing complex (GO:0032991)

Reactome top-level categories

15 top-level categories:

Category	Pathways
Transcriptional regulation by RUNX1	2
ESR-mediated signaling	2
Developmental Lineages of the Mammary Gland	2
Signaling by ERBB4	1
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
Generic Transcription Pathway	1
SUMO E3 ligases SUMOylate target proteins	1
Deubiquitination	1
Negative regulation of the PI3K/AKT network	1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1
Signaling by Nuclear Receptors	1
Transcriptional regulation by RUNX2	1
Cellular responses to stress	1
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

showing 60 of 76 GO namespaces:

Category	Terms
cellular anatomical structure	5
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
protein binding	3
DNA-templated transcription	2
regulation of gene expression	2
nitric-oxide synthase activity	2
chromatin	2
transcription coregulator binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
intracellular membrane-bounded organelle	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
chromatin organization	1
regulation of RNA biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
regulation of biological quality	1
gene expression	1
negative regulation of macromolecule biosynthetic process	1
steroid hormone receptor signaling pathway	1
nuclear receptor-mediated signaling pathway	1
nuclear receptor-mediated steroid hormone signaling pathway	1
response to lipid	1
response to oxygen-containing compound	1
negative regulation of muscle cell apoptotic process	1
smooth muscle cell apoptotic process	1
regulation of smooth muscle cell apoptotic process	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
hormone-mediated signaling pathway	1
cellular response to steroid hormone stimulus	1
response to hormone	1
nitric oxide biosynthetic process	1
positive regulation of biosynthetic process	1
regulation of nitric oxide biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cell differentiation	1
regulation of nitric-oxide synthase activity	1
positive regulation of oxidoreductase activity	1
cis-regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
RNA polymerase II general transcription initiation factor binding	1
transcription factor binding	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
intracellular receptor signaling pathway	1
signaling receptor activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 41 of 69 annotations. The rest are phylogenetic / computational / electronic (IEA).

41 experimentally-supported GO terms:

GO term	NS	Evidence
RNA polymerase II preinitiation complex assembly	BP	direct assay
cellular response to estradiol stimulus	BP	direct assay
estrogen receptor signaling pathway	BP	direct assay
negative regulation of canonical NF-kappaB signal transduction	BP	direct assay
negative regulation of gene expression	BP	direct assay
negative regulation of miRNA transcription	BP	mutant phenotype
negative regulation of transcription by RNA polymerase II	BP	mutant phenotype
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of nitric oxide biosynthetic process	BP	direct assay
positive regulation of nitric-oxide synthase activity	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
protein localization to chromatin	BP	mutant phenotype
response to estradiol	BP	direct assay
response to estrogen	BP	direct assay
steroid hormone receptor signaling pathway	BP	mutant phenotype
chromatin	CC	direct assay
cytoplasm	CC	direct assay
euchromatin	CC	direct assay
nucleus	CC	direct assay
plasma membrane	CC	direct assay
protein-containing complex	CC	direct assay
14-3-3 protein binding	MF	physical interaction
ATPase binding	MF	direct assay
DNA-binding transcription activator activity, RNA polymerase II-specific	MF	direct assay
RNA polymerase II cis-regulatory region sequence-specific DNA binding	MF	direct assay
TBP-class protein binding	MF	physical interaction
TFIIB-class transcription factor binding	MF	physical interaction
beta-catenin binding	MF	physical interaction
calmodulin binding	MF	experiment
chromatin binding	MF	direct assay
enzyme binding	MF	physical interaction
estrogen response element binding	MF	direct assay
identical protein binding	MF	physical interaction
nuclear estrogen receptor activity	MF	direct assay
nuclear estrogen receptor binding	MF	physical interaction
nuclear receptor activity	MF	direct assay
protein kinase binding	MF	physical interaction
sequence-specific double-stranded DNA binding	MF	direct assay
transcription coactivator binding	MF	physical interaction
transcription coregulator binding	MF	physical interaction
transcription corepressor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 7,435 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ESR1	ERBB2	P04626	965
ESR1	GPER1	Q99527	938
ESR1	CYP19A1	P11511	916
ESR1	TP53	P04637	904
ESR1	EGFR	P00533	898
ESR1	GREB1	Q4ZG55	869
ESR1	NCOA3	Q9Y6Q9	865
ESR1	BRCA1	P38398	863
ESR1	MYC	P01106	824
ESR1	NCOA1	Q15788	812
ESR1	ACTB	P02570	811
ESR1	PGR	P06401	806
ESR1	CDH1	P12830	802
ESR1	SRC	P12931	800
ESR1	AKT1	P31749	797

IntAct

Human interaction partners of ESR1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 123 partners by confidence:

Partner	Interaction type	MIscore	Records
SRC	association	0.850	13
NCOA1	association	0.840	8
RELA	direct interaction	0.830	7
BRCA1	direct interaction	0.810	14
PGR	physical association	0.770	22
PRMT2	colocalization	0.750	9
ATAD2	physical association	0.740	3
MACROD1	physical association	0.690	6
NCOA3	physical association	0.690	1
CCN2	physical association	0.680	7
NFKB1	direct interaction	0.680	3
SP3	direct interaction	0.670	2
JMJD6	physical association	0.650	8
ASF1A	direct interaction	0.650	2
RAC3	direct interaction	0.640	5
TRIM24	association	0.640	3
MYL6	direct interaction	0.640	1
ARID5A	physical association	0.630	9
FOXO3	physical association	0.630	7
ZNF366	physical association	0.630	6
PPP5C	physical association	0.630	4
GATA3	association	0.620	1
GRIP1	direct interaction	0.610	2
PELP1	association	0.600	1
RARA	association	0.600	1
AKAP13	direct interaction	0.590	3
LINC00312	physical association	0.590	3
ATF1	direct interaction	0.590	1
CEBPB	direct interaction	0.590	1
EDF1	direct interaction	0.590	1

BioGRID (3,444 interactions; top human partners by supporting records in a sample of 600 records): BRCA1 (Affinity Capture-Western; 10 records), NCOA1 (Reconstituted Complex; 10 records), SRC (Reconstituted Complex; 10 records), AHR (Reconstituted Complex; 9 records), NCOA3 (Reconstituted Complex; 9 records), EP300 (Reconstituted Complex; 8 records), CREBBP (Affinity Capture-Western; 6 records), PBXIP1 (Two-hybrid; 5 records), BCAS3 (Reconstituted Complex; 4 records), FOXK2 (Affinity Capture-Western; 4 records), MTA1 (Affinity Capture-Western; 4 records), NCOA2 (Reconstituted Complex; 4 records), NCOA6 (Reconstituted Complex; 4 records), SMARCE1 (Reconstituted Complex; 4 records), TAB2 (Reconstituted Complex; 4 records)

SIGNOR signaling

showing 40 of 141 signaling interactions:

A	Effect	B	Mechanism
ESR1	“up-regulates quantity by expression”	NCOA2	“transcriptional regulation”
NR0B2	down-regulates	ESR1	binding
EGFR	up-regulates	ESR1	phosphorylation
ERBB2	up-regulates	ESR1	phosphorylation
PRKACA	up-regulates	ESR1	phosphorylation
ESR1	“up-regulates quantity by expression”	CCND1	“transcriptional regulation”
MAPK14	up-regulates	ESR1	phosphorylation
GSK3B	up-regulates	ESR1	phosphorylation
ESR1	“down-regulates quantity by repression”	PPARG	“transcriptional regulation”
ESR1	up-regulates	PIK3R1	binding
ESR1	up-regulates	PIK3R2	binding
KMT2D	up-regulates	ESR1	binding
“MLL2 complex”	up-regulates	ESR1	binding
17beta-estradiol	up-regulates	ESR1	“chemical activation”
MAPK1	up-regulates	ESR1	phosphorylation
MAPK3	up-regulates	ESR1	phosphorylation
IKBKE	up-regulates	ESR1	phosphorylation
CSNK2A1	down-regulates	ESR1	phosphorylation
ABL1	up-regulates	ESR1	phosphorylation
RPS6KA3	up-regulates	ESR1	phosphorylation
CDK2	up-regulates	ESR1	phosphorylation
CyclinA2/CDK2	up-regulates	ESR1	phosphorylation
POU4F2	“up-regulates activity”	ESR1	binding
POU4F1	“up-regulates activity”	ESR1	binding
AKT	up-regulates	ESR1	phosphorylation
ERK1/2	up-regulates	ESR1	phosphorylation
DUSP22	“down-regulates activity”	ESR1	dephosphorylation
ESR1	up-regulates	PI3K	binding
RPS6K	up-regulates	ESR1	phosphorylation
ESR1	“down-regulates quantity by repression”	SCN5A	“transcriptional regulation”
AIP	“down-regulates activity”	ESR1	“transcriptional regulation”
ESR1	“up-regulates quantity by expression”	TFF1	“transcriptional regulation”
ESR1	“up-regulates quantity by expression”	CDKN1A	“transcriptional regulation”
ESR1	unknown	MYC	“transcriptional regulation”
ESR1	“up-regulates quantity by expression”	TGFA	“transcriptional regulation”
BRCA1	“down-regulates activity”	ESR1
MECP2	“down-regulates quantity by repression”	ESR1	“transcriptional regulation”
DNMT1	“down-regulates quantity by repression”	ESR1	“transcriptional regulation”
HDAC1	“down-regulates quantity by repression”	ESR1	“transcriptional regulation”
ESR1	“up-regulates quantity by expression”	F12	“transcriptional regulation”

Protein complexes (CORUM) (66)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

showing 60 of 66 complexes by size:

Complex	Subunits	Members
★ ESR1-Mediator complex	18	CDK8, MED1, MED12, MED21, MED24, EP300, MED17, MED6, MED16, NCOA1, ESR1, MED10, MED13, MED14, MED20, MED23, MED7, CCNC
★ TFTC-type histone acetyl transferase complex	11	MED17, MED1, MED12, MED13, MED14, MED16, MED23, MED24, TRRAP, ESR1, KAT2A
★ MegaTrans complex	10	ESR1, FOS, GATA3, STAT1, XRCC5, XRCC6, FOXA1, PRKDC, RARA, TFAP2C
★ MegaTrans complex	10	FOS, FOXA1, STAT1, XRCC5, XRCC6, ESR1, GATA3, PRKDC, RARG, TFAP2C
★ CDK7-CCNH-ESR1-HDAC2-MNAT1-MTA1 complex	6	CCNH, CDK7, ESR1, HDAC2, MNAT1, MTA1
★ BCL3-ESR1-NCOA3-RELA complex	4	BCL3, ESR1, NCOA3, RELA
★ BCAR1-ESR1-PIK3R1-SRC complex	4	BCAR1, ESR1, PIK3R1, SRC
★ ESR1-IGF1R-SHC1 complex	4	ESR1, IGF1R, SHC1
★ AJUBA-CCAR2-CREBBP-ESR1 complex	4	CREBBP, ESR1, AJUBA, CCAR2
★ CTBP1-ESR1-LCOR-RBBP8 complex	4	CTBP1, ESR1, LCOR, RBBP8
★ ESR1-KDM3A-TNK2 complex	3	ESR1, KDM3A, TNK2
★ CHUK-ESR1-NCOA3 complex	3	NCOA3, CHUK, ESR1
★ ESR1-MDM2-TP53 complex	3	ESR1, MDM2, TP53
★ ESR1-GRIP1-JUN complex	3	ESR1, GRIP1, JUN
★ EP300-ESR1-NCOA1 complex	3	ESR1, NCOA1, EP300
★ CAV1-ESR1-VDAC1 complex	3	VDAC1, CAV1, ESR1
★ ESR1-EP300-NCOA2 complex	3	EP300, ESR1, NCOA2
★ ESR1-PELP1-SRC complex	3	ESR1, PELP1, SRC
★ ESR1-MAGEA2-TP53 complex	3	ESR1, MAGEA2, TP53
★ CCND1-ESR1-NCOA1 complex	3	ESR1, NCOA1, CCND1
★ CALCOCO1-ESR1-NCOA2 complex	3	CALCOCO1, ESR1, NCOA2
★ ESR1-NCOA3-NCOR2 complex	3	NCOA3, NCOR2, ESR1
★ ERS1-GSK3B complex	2	ESR1, GSK3B
★ ESR1-JUN complex	2	ESR1, JUN
★ ESR1-SP1 complex	2	SP1, ESR1
★ CEBPB-ESR1 complex	2	CEBPB, ESR1
★ ERS1-MDM2 complex	2	ESR1, MDM2
★ ESR1-MDM4 complex	2	ESR1, MDM4
★ CTNNB1-ESR1 complex	2	CTNNB1, ESR1
★ ESR1-FOXO1 complex	2	ESR1, FOXO1
★ DNAAF4-ESR1 complex	2	ESR1, DNAAF4
★ ESR1-NCOA2 complex	2	ESR1, NCOA2
★ AR-ESR1 complex	2	AR, ESR1
★ ESR1-SVIL complex	2	ESR1, SVIL
★ ESR1-SORBS3 complex	2	ESR1, SORBS3
★ ESR1-TCF4 complex	2	ESR1, TCF4
★ CDC25B-ESR1 complex	2	CDC25B, ESR1
★ ANP32A-ESR1 complex	2	ANP32A, ESR1
★ ESR1-RBAK complex	2	ESR1, RBAK
★ ESR1-TRIP4 complex	2	ESR1, TRIP4
★ ESR1-PNRC1 complex	2	ESR1, PNRC1
★ ARID5A-ESR1 complex	2	ARID5A, ESR1
★ ESR1-UXT complex	2	ESR1, UXT
★ ESR1-NCOA3 complex	2	NCOA3, ESR1
★ ESR1-NCOA1 complex	2	ESR1, NCOA1
★ BRCA1-ESR1 complex	2	BRCA1, ESR1
★ CITED1-ESR1 complex	2	CITED1, ESR1
★ ESR1-UBE3A complex	2	ESR1, UBE3A
★ ERBB4-ESR1 complex	2	ESR1, ERBB4
★ ESR1-MED1 complex	2	ESR1, MED1
★ ESR1-PHB2 complex	2	ESR1, PHB2
★ ESR1-RBM23 complex	2	ESR1, RBM23
★ CCDC62-ESR1 complex	2	CCDC62, ESR1
★ DNTTIP2-ESR1 complex	2	DNTTIP2, ESR1
★ ESR1-NCOA5 complex	2	ESR1, NCOA5
★ ESR1-NCOA6 complex	2	ESR1, NCOA6
★ ESR1-NCOA7 complex	2	ESR1, NCOA7
★ ESR1-PRMT2 complex	2	ESR1, PRMT2
★ ESR1-TXNRD1 complex	2	ESR1, TXNRD1
★ ESR1-SETD7 complex	2	ESR1, SETD7

Ligand–receptor pairs (CellPhoneDB) (3)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

3 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
HSD17B1	receptor	Signaling by Estradiol
CYP19A1	receptor	Signaling by Steroids
UBASH3B	receptor	Signaling by Dehydroepiandrosterone

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
R-HSA-1368082	5	35.7×	7e-06
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	8	32.6×	9e-09
BMAL1:CLOCK,NPAS2 activates circadian expression	6	25.4×	4e-06
Expression of BMAL (ARNTL), CLOCK, and NPAS2	8	23.4×	1e-07
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	10	19.7×	9e-09
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	9	19.4×	7e-08
Regulation of cholesterol biosynthesis by SREBP (SREBF)	6	19.0×	2e-05
Transcriptional regulation of white adipocyte differentiation	14	18.2×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to estrogen stimulus	6	47.2×	5e-07
host-mediated activation of viral transcription	5	37.3×	3e-05
positive regulation of transforming growth factor beta receptor signaling pathway	5	22.1×	2e-04
positive regulation of miRNA transcription	8	19.5×	2e-06
response to estrogen	6	17.3×	1e-04
T cell differentiation in thymus	5	17.3×	7e-04
cellular response to hormone stimulus	5	16.1×	8e-04
transcription initiation-coupled chromatin remodeling	5	16.1×	8e-04

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

ESR1 has been a focus in breast cancer for quite some time, but is also clinically relevant in endometrial, ovarian and other cancer types. The identification of ER-positive breast cancers that are resistant to hormone therapy have inspired clinical sequencing efforts to shed light on the mechanisms of this resistance. A number of mutations in the ligand binding domain of ESR1 have been implicated in hormone resistance and anti-estrogen therapies. These observations have spurred efforts to develop therapeutics that stimulate ESR1 protein degradation (e.g. Fulvestrant), rather than acting as a small molecule antagonist. These agents are currently in clinical trials and have seen some success.

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — BRCA, LUSC, MEL, UCEC.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for ESR1: 230 ClinVar records (3 pathogenic / likely pathogenic); 8 CIViC cancer variants; 12 PharmGKB clinical annotations; 126 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

230 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	86
Likely benign	62
Benign	46

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
60557	NM_000125.4(ESR1):c.1125G>T (p.Gln375His)	Pathogenic	no assertion criteria provided	2
16590	NM_000125.4(ESR1):c.1339_1340delinsGC (p.Cys447Ala)	Pathogenic	no assertion criteria provided	1
16592	NM_000125.4(ESR1):c.469C>T (p.Arg157Ter)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ESR1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 39 predictions of 1,669):

Position(s)	Effect	Δscore	Sites
6:151842595–151842596	acceptor_loss	1.0000	5
6:151842596	acceptor_gain	1.0000
6:151842788–151842789	donor_loss	1.0000	5
6:151880653–151880654	acceptor_loss	1.0000	6
6:151944509–151944510	donor_loss	1.0000	5
6:152011759	donor_gain	1.0000
6:152011795–152011796	donor_loss	1.0000	4
6:151808365–151808366	donor_loss	0.9900	5
6:151880651	acceptor_gain	0.9900
6:151880772–151880773	donor_loss	0.9900	6

AlphaMissense

1,397 missense substitutions predicted likely pathogenic (of 3,910 scored), across 294 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M250	9	0.997	1.000
M543	9	0.960	0.999
M343	9	0.931	0.994
M357	9	0.891	0.993
H196	8	1.000	1.000
D190	8	0.999	1.000
F208	8	0.999	1.000
F209	8	0.998	1.000
D230	8	0.993	0.999
S212	8	0.984	1.000
D351	8	0.979	0.997
S236	8	0.973	0.999
F404	8	0.973	0.999
F367	8	0.972	0.999
D426	8	0.956	0.992
F425	8	0.940	0.995
D538	8	0.932	0.979
H524	8	0.929	0.994
D374	8	0.900	0.960
D218	8	0.861	0.969

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Breast Invasive Carcinoma, Uterine Corpus Endometrial Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	favorable	1.09e-09
Liver Hepatocellular Carcinoma (TCGA)	favorable	3.29e-05
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	0.000123
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000301

Disease associations

OMIM: gene MIM:133430 | disease phenotypes: MIM:615363, MIM:618484

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
estrogen resistance syndrome	Strong	Autosomal recessive	4

Mondo (3): estrogen resistance syndrome (MONDO:0014148), cleft lip/palate (MONDO:0016044), arthrogryposis multiplex congenita 3, myogenic type (MONDO:0032778)

Orphanet (2): Estrogen resistance syndrome (Orphanet:785), Cleft lip/palate (Orphanet:199306)

HPO phenotypes

43 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000098	Tall stature
HP:0000147	Polycystic ovaries
HP:0000613	Photophobia
HP:0000786	Primary amenorrhea
HP:0000823	Delayed puberty
HP:0000834	Abnormality of the adrenal glands
HP:0000837	Increased circulating gonadotropin level
HP:0000842	Hyperinsulinemia
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000956	Acanthosis nigricans
HP:0001061	Acne
HP:0001442	Typified by somatic mosaicism
HP:0001548	Overgrowth
HP:0001677	Coronary artery atherosclerosis
HP:0001952	Glucose intolerance
HP:0002013	Vomiting
HP:0002018	Nausea
HP:0002077	Migraine with aura
HP:0002083	Migraine without aura
HP:0002183	Phonophobia
HP:0002574	Episodic abdominal pain
HP:0002663	Delayed epiphyseal ossification
HP:0002750	Delayed skeletal maturation
HP:0003002	Breast carcinoma
HP:0003117	Abnormal circulating hormone concentration
HP:0003187	Breast hypoplasia
HP:0003621	Juvenile onset
HP:0003799	Marked delay in bone age
HP:0008187	Absence of secondary sex characteristics
HP:0008197	Absence of pubertal development
HP:0008675	Enlarged polycystic ovaries
HP:0010639	Elevated alkaline phosphatase of bone origin
HP:0010679	Elevated tissue non-specific alkaline phosphatase
HP:0025134	Increased serum estradiol
HP:0030087	Abnormal circulating testosterone concentration
HP:0031428	Increased circulating osteocalcin level
HP:0040270	Impaired glucose tolerance
HP:0100133	Abnormality of the pubic hair
HP:0100783	Breast aplasia

GWAS associations

showing 30 of 126 associations:

Study	Trait	p-value
GCST006433_307	Heel bone mineral density	0.000000e+00
GCST006433_308	Heel bone mineral density	2e-212
GCST006979_82	Heel bone mineral density	1e-138
GCST009120_3	Heel bone mineral density	9e-130
GCST006288_14	Heel bone mineral density	2e-119
GCST006288_171	Heel bone mineral density	2e-61
GCST006288_755	Heel bone mineral density	1e-54
GCST009158_26	Uterine fibroids	2e-54
GCST004988_324	Breast cancer	5e-54
GCST008839_541	Height	9e-46
GCST004988_51	Breast cancer	3e-41
GCST90000047_54	Age at first sexual intercourse	8e-38
GCST90000025_1018	Appendicular lean mass	1e-37
GCST006288_79	Heel bone mineral density	7e-35
GCST007269_202	Pulse pressure	6e-32
GCST005076_31	Breast cancer (estrogen-receptor negative)	3e-31
GCST008362_196	Birth weight	1e-28
GCST003845_9	Breast cancer	4e-28
GCST007096_17	Pulse pressure	8e-28
GCST006979_83	Heel bone mineral density	2e-27
GCST004988_128	Breast cancer	1e-26
GCST002647_152	Height	8e-24
GCST001937_11	Breast cancer	2e-21
GCST006288_756	Heel bone mineral density	5e-21
GCST005146_34	Birth weight	6e-20
GCST003845_8	Breast cancer	1e-19
GCST90000050_45	Age at first birth	3e-19
GCST006423_4	Fracture	5e-19
GCST004278_19	Pulse pressure	2e-18
GCST005076_24	Breast cancer (estrogen-receptor negative)	2e-18

EFO canonical traits (from GWAS)

30 canonical traits:

EFO ID	Trait name
EFO:0004278	sudden cardiac arrest
EFO:0003940	physical activity
EFO:0005654	velocity of sound measurement
EFO:0004514	bone quantitative ultrasound measurement
EFO:0004703	age at menarche
EFO:0005941	mammographic density measurement
EFO:0006503	dense area measurement
EFO:0007701	spine bone mineral density
EFO:0007785	femoral neck bone mineral density
EFO:0006527	smoking status measurement
EFO:0009101	age at first birth measurement
EFO:0005763	pulse pressure measurement
EFO:0008111	diet measurement
EFO:0008307	tuberculin skin test reactivity measurement
EFO:0008322	decreased susceptibility to bacterial infection
EFO:0004344	birth weight
EFO:0009270	heel bone mineral density
EFO:0009443	BRCAX breast cancer
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004341	body fat distribution
EFO:0009749	age at first sexual intercourse measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0005939	parental genotype effect measurement
EFO:0009863	anxiety measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004750	interleukin 10 measurement
EFO:0600067	mastiha supplement exposure measurement
EFO:0004980	appendicular lean mass
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (9): CHEMBL206 (SINGLE PROTEIN), CHEMBL2093866 (PROTEIN FAMILY), CHEMBL3885521 (PROTEIN COMPLEX), CHEMBL4523681 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523713 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523721 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523726 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523754 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193788 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ESR1 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

22 curated-mechanism drugs:

Drug	Modality	Max phase
CLOMIPHENE CITRATE	Small molecule	4
DIENESTROL	Small molecule	4
DIETHYLSTILBESTROL	Small molecule	4
ELACESTRANT	Small molecule	4
ESTRADIOL	Small molecule	4
ESTRADIOL CYPIONATE	Small molecule	4
ESTRADIOL VALERATE	Small molecule	4
ESTRONE	Small molecule	4
ESTROPIPATE	Small molecule	4
ETHINYL ESTRADIOL	Small molecule	4
FULVESTRANT	Small molecule	4
MESTRANOL	Small molecule	4
POLYESTRADIOL PHOSPHATE	Small molecule	4
RALOXIFENE	Small molecule	4
TAMOXIFEN CITRATE	Small molecule	4
AMCENESTRANT	Small molecule	3
CAMIZESTRANT	Small molecule	3
ENCLOMIPHENE	Small molecule	3
GIREDESTRANT	Small molecule	3
BRILANESTRANT	Small molecule	2
GTX-758	Small molecule	2
TAS-108	Small molecule	2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes ESR1 — the drug acts on the assembly or class, not necessarily on this subunit alone.

23 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
BAZEDOXIFENE ACETATE	Estrogen receptor	2	4
CYCLOFENIL	Estrogen receptor	2	4
DIETHYLSTILBESTROL DIPHOSPHATE	Estrogen receptor	2	4
ESTETROL	Estrogen receptor	2	4
ESTRIOL	Estrogen receptor	2	4
ESTROGENS, CONJUGATED	Estrogen receptor	2	4
ESTROGENS, CONJUGATED SYNTHETIC A	Estrogen receptor	2	4
ESTROGENS, ESTERIFIED	Estrogen receptor	2	4
LASOFOXIFENE	Estrogen receptor	2	4
OSPEMIFENE	Estrogen receptor	2	4
QUINESTROL	Estrogen receptor	2	4
SYNTHETIC CONJUGATED ESTROGENS, B	Estrogen receptor	2	4
TOREMIFENE CITRATE	Estrogen receptor	2	4
ACOLBIFENE	Estrogen receptor	2	3
AFIMOXIFENE	Estrogen receptor	2	3
ARZOXIFENE	Estrogen receptor	2	3
DROLOXIFENE	Estrogen receptor	2	3
ALLYLESTRENOL	Estrogen receptor	2	2
FISPEMIFENE	Estrogen receptor	2	2
IDOXIFENE	Estrogen receptor	2	2
LY2245461	Estrogen receptor	2	2
MK-6913	Estrogen receptor	2	2
CHF4227	Estrogen receptor	2	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,089,676 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 162 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL2355051	CLOMIPHENE	4	36
CHEMBL1018	DIENESTROL	4	5,645
CHEMBL411	DIETHYLSTILBESTROL	4	373,838
CHEMBL4297509	ELACESTRANT	4	1,164
CHEMBL135	ESTRADIOL	4	124,045
CHEMBL1200430	ESTRADIOL ACETATE	4	1,127
CHEMBL1200973	ESTRADIOL CYPIONATE	4	4,113
CHEMBL1511	ESTRADIOL VALERATE	4	7,361
CHEMBL1405	ESTRONE	4	36,940
CHEMBL691	ETHINYL ESTRADIOL	4	40,893
CHEMBL1358	FULVESTRANT	4	57,485
CHEMBL1201151	MESTRANOL	4	10,396
CHEMBL81	RALOXIFENE	4	78,815
CHEMBL1116	RALOXIFENE HYDROCHLORIDE	4	28,863
CHEMBL83	TAMOXIFEN	4	173,287
CHEMBL786	TAMOXIFEN CITRATE	4	82,863
CHEMBL1085	ACETOPHENAZINE	4	5,157
CHEMBL1738797	ALECTINIB	4	7,111
CHEMBL53	APOMORPHINE	4	26,040
CHEMBL1112	ARIPIPRAZOLE	4	24,497
CHEMBL25	ASPIRIN	4
CHEMBL158	AZTREONAM	4
CHEMBL46740	BAZEDOXIFENE	4
CHEMBL408513	BELINOSTAT	4
CHEMBL388590	BENZBROMARONE	4
CHEMBL1023	BEXAROTENE	4
CHEMBL942	BISACODYL	4
CHEMBL290106	BITHIONOL	4
CHEMBL493	BROMOCRIPTINE	4
CHEMBL1295	BUTOCONAZOLE	4
CHEMBL1014	CANDESARTAN CILEXETIL	4
CHEMBL1630575	CASPOFUNGIN	4
CHEMBL1644	CEFADROXIL	4
CHEMBL186	CEFEPIME	4
CHEMBL44354	CEFTAZIDIME	4
CHEMBL1477	CERIVASTATIN	4
CHEMBL1200761	CHLOROTRIANISENE	4
CHEMBL11359	CISPLATIN	4
CHEMBL1292	CLOFAZIMINE	4
CHEMBL141305	CYCLOFENIL	4
CHEMBL1479	DANAZOL	4
CHEMBL178	DAUNORUBICIN	4
CHEMBL333826	DEQUALINIUM	4
CHEMBL1533	DESOGESTREL	4
CHEMBL548	DINOPROSTONE	4
CHEMBL53463	DOXORUBICIN	4
CHEMBL184412	DRONEDARONE	4
CHEMBL1536	ERGOCALCIFEROL	4
CHEMBL1359	ERTAPENEM	4
CHEMBL1230314	ESTETROL ANHYDROUS	4
CHEMBL1756	ESTRAMUSTINE PHOSPHATE	4
CHEMBL193482	ESTRIOL	4
CHEMBL1200623	ETHYLESTRENOL	4
CHEMBL1200624	ETHYNODIOL DIACETATE	4
CHEMBL1531	ETONOGESTREL	4
CHEMBL308954	ETRAVIRINE	4
CHEMBL255044	FLUPIRTINE	4
CHEMBL496	HEXACHLOROPHENE	4
CHEMBL9225	HEXESTROL	4
CHEMBL521	IBUPROFEN	4

Clinical evidence (CIViC)

Drug × variant × indication, from 31 curated evidence items; also 2 functional. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

29 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
ESR1 D538G	Elacestrant	Estrogen Receptor-positive Breast Cancer	Sensitivity/Response	CIViC A	EID12219
ESR1 L536Q	Elacestrant	Estrogen Receptor-positive Breast Cancer	Sensitivity/Response	CIViC A	EID12229
ESR1 Mutation	Elacestrant	Breast Cancer	Sensitivity/Response	CIViC A	EID11443
ESR1 Mutation	Imlunestrant Regimen + Abemaciclib Regimen	Breast Carcinoma	Sensitivity/Response	CIViC A	EID12599
ESR1 Mutation	Fulvestrant + Aromatase Inhibitor + Imlunestrant Regimen	Breast Carcinoma	Sensitivity/Response	CIViC A	EID12600
ESR1 S463P	Elacestrant	Estrogen Receptor-positive Breast Cancer	Sensitivity/Response	CIViC A	EID12230
ESR1 Y537C	Elacestrant	Estrogen Receptor-positive Breast Cancer	Sensitivity/Response	CIViC A	EID12222
ESR1 Y537N	Elacestrant	Estrogen Receptor-positive Breast Cancer	Sensitivity/Response	CIViC A	EID12221
ESR1 Y537S	Elacestrant	Estrogen Receptor-positive Breast Cancer	Sensitivity/Response	CIViC A	EID12220
ESR1 Y537N	Palbociclib	Breast Cancer	Sensitivity/Response	CIViC B	EID4817 +1
ESR1 Y537S	Palbociclib	Breast Cancer	Sensitivity/Response	CIViC B	EID4819 +1
ESR1 Overexpression	Palbociclib + Letrozole	Breast Cancer	Sensitivity/Response	CIViC B	EID1541
ESR1 Y537S	Selective Estrogen Receptor Covalent Antagonist H3B-6545	Breast Carcinoma	Sensitivity/Response	CIViC B	EID12616
PIK3CA Mutation OR RB1 Mutation OR ESR1 Mutation	Fulvestrant + Palbociclib	Breast Cancer	Resistance	CIViC B	EID12045
ESR1 D538G	Palbociclib	Breast Cancer	Sensitivity/Response	CIViC C	EID4813
ESR1 D538G	Palbociclib + Letrozole	Breast Cancer	Sensitivity/Response	CIViC C	EID4814
ESR1 S463P	Palbociclib	Breast Cancer	Sensitivity/Response	CIViC C	EID4815
ESR1 Y537C	Palbociclib	Breast Cancer	Sensitivity/Response	CIViC C	EID4812
ESR1 D538G	Fulvestrant + Tamoxifen	Breast Cancer	Sensitivity/Response	CIViC D	EID291
ESR1 L536Q	Tamoxifen + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC D	EID290
ESR1 Y537C	Fulvestrant + Tamoxifen	Breast Cancer	Sensitivity/Response	CIViC D	EID292
ESR1 Y537N	Fulvestrant + Tamoxifen	Breast Cancer	Sensitivity/Response	CIViC D	EID293
ESR1 Y537S	Fulvestrant + Tamoxifen	Breast Cancer	Sensitivity/Response	CIViC D	EID294
ESR1 D538G	Hormone Therapy	Breast Cancer	Resistance	CIViC D	EID243
ESR1 L536Q	Hormone Therapy	Breast Cancer	Resistance	CIViC D	EID242
ESR1 S463P	Aromatase Inhibitor	Estrogen Receptor-positive Breast Cancer	Resistance	CIViC D	EID1727
ESR1 Y537C	Hormone Therapy	Breast Cancer	Resistance	CIViC D	EID244
ESR1 Y537N	Hormone Therapy	Breast Cancer	Resistance	CIViC D	EID245
ESR1 Y537S	Hormone Therapy	Breast Cancer	Resistance	CIViC D	EID246

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

CIViC curated variants (8)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

Mutation, L536Q (missense variant), D538G (missense variant), Y537C (missense variant), Y537N (missense variant), Y537S (missense variant), Overexpression, S463P (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

12 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs11543791	Efficacy	3	raloxifene	Menopause;Schizophrenia
rs2207396	Toxicity	3	Alkylating Agents;cisplatin	Neoplasms
rs2234693	Toxicity	3	anastrozole;letrozole	Neoplasms
rs2234693	Efficacy	3	leflunomide	Rheumatoid arthritis
rs2234693	Toxicity	3	methamphetamine	Psychotic Disorder
rs2813543	Toxicity	3	exemestane	Breast Neoplasms
rs4870061	Toxicity	3	letrozole	Breast Neoplasms
rs9322335	Toxicity	3	exemestane;letrozole	Breast Neoplasms
rs9340799	Toxicity	3	tamoxifen
rs9340799	Efficacy	3	leflunomide	Rheumatoid arthritis
rs9340799	Efficacy	3	conjugated estrogens;medroxyprogesterone
rs9340799	Toxicity	3	anastrozole;letrozole	Neoplasms

PharmGKB variants

6 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2207396	ESR1	3	2.50	1	Alkylating Agents;cisplatin
rs2234693	ESR1	3	2.75	3	methamphetamine;anastrozole;letrozole;leflunomide
rs2813543	ESR1	3	2.50	1	exemestane
rs4870061	ESR1	3	5.00	1	letrozole
rs9322335	ESR1	3	5.00	1	exemestane;letrozole
rs9340799	ESR1	3	2.75	4	tamoxifen;leflunomide;conjugated estrogens;medroxyprogesterone;anastrozole;letrozole

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

18 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2234693	anastrozole, letrozole	Other	Allele C is associated with increased risk of musculoskeletal pain when exposed to anastrozole and letrozole in women with early breast cancer as compared to allele T.	PMID:23894347
rs9340799	anastrozole, letrozole	Other	Allele A is associated with increased risk of musculoskeletal pain when exposed to anastrozole and letrozole in women with early breast cancer as compared to allele G.	PMID:23894347
rs4870061	exemestane, letrozole	Toxicity	Genotypes CT + TT are associated with decreased bone density when treated with exemestane or letrozole in women with Breast Neoplasms as compared to genotype CC.	PMID:26536870
rs9322335	exemestane, letrozole	Toxicity	Genotype TT is associated with decreased bone density when treated with exemestane or letrozole in women with Breast Neoplasms as compared to genotypes CC + CT.	PMID:26536870
rs4870061	letrozole	Toxicity	Genotype TT is associated with decreased bone density when treated with letrozole in women with Breast Neoplasms as compared to genotypes CC + CT.	PMID:26536870
rs9322335	letrozole	Toxicity	Genotype TT is associated with decreased bone density when treated with letrozole in women with Breast Neoplasms as compared to genotypes CC + CT.	PMID:26536870
rs2813543	exemestane	Toxicity	Genotype AA is associated with decreased bone density when treated with exemestane in women with Breast Neoplasms as compared to genotypes AG + GG.	PMID:26536870
rs2077647	glyburide	Efficacy	Allele T is associated with increased response to glibenclamide in people with as compared to allele C.	PMID:27403931
rs11543791	raloxifene	Efficacy	Genotype CC is associated with decreased response to raloxifene in women Menopause and Schizophrenia as compared to genotypes CT + TT.	PMID:27546373
rs2234693	raloxifene	Efficacy	Genotype TT is associated with increased clinical benefit to raloxifene in people with Schizophrenia or Schizoaffective disorder as compared to genotypes CC + CT.	PMID:39799793
rs9340799	tamoxifen	Other	Genotype GG is associated with decreased in total cholesterol in postmenopausal woman and increase in triglycerides and decrease in high density lipoprotein in premenopausal women when treated with tamoxifen as compared to genotypes AA + AG.	PMID:17713466
rs2207396	Alkylating Agents, cisplatin	Toxicity	Allele A is associated with increased risk of Oligospermia when treated with Alkylating Agents and cisplatin in people with childhood cancer as compared to genotype GG.	PMID:21430602
rs9340799	leflunomide	Efficacy	Genotype AA is associated with increased response to leflunomide in women with Arthritis, Rheumatoid as compared to genotypes AG + GG.	PMID:21174621
rs2234693	leflunomide	Efficacy	Genotype TT is associated with increased response to leflunomide in women with Arthritis, Rheumatoid as compared to genotype CC.	PMID:21174621
rs2234693	methamphetamine	Toxicity	Genotype CC is associated with increased likelihood of Psychotic Disorders due to methamphetamine in men as compared to genotypes CT + TT.	PMID:19386276
rs9340799	tamoxifen	Toxicity	Genotypes AG + GG are associated with increased risk of Venous thromboembolism when treated with tamoxifen in people with Breast Neoplasms.	PMID:19082882
rs9322336	exemestane	Toxicity	Genotype CC is associated with increased likelihood of musculoskeletal toxicity when treated with exemestane in women with Breast Neoplasms.	PMID:23546553
rs2234693	dexamethasone	Toxicity	Genotypes CC + CT are not associated with increased risk of Osteonecrosis when treated with dexamethasone in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.	PMID:18285546

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: nhr — 3A. Estrogen receptors

Most potent curated ligand interactions (32 total), top 25:

Ligand	Action	Affinity	Parameter
diethylstilbestrol	Agonist	10.4	pKi
giredestrant	Antagonist	10.3	pIC50
hexestrol	Antagonist	10.3	pKi
4-hydroxytamoxifen	Agonist	9.85	pKi
17β-estradiol	Agonist	9.82	pKi
camizestrant	Antagonist	9.8	pIC50
propylpyrazoletriol	Agonist	9.64	pKi
LSZ102	Antagonist	9.52	pIC50
imlunestrant	Antagonist	9.51	pKi
raloxifene	Agonist	9.5	pKi
16α-hydroxyestrone	Agonist	9.15	pKd
fulvestrant	Antagonist	8.98	pKi
clomiphene	Antagonist	8.89	pKi
compound 5 [PMID: 40393772]	Antagonist	8.8	pIC50
ethinylestradiol	Agonist	8.7	pIC50
estriol	Agonist	8.67	pKi
methyl-piperidino-pyrazole	Antagonist	8.57	pKi
lasofoxifene	Partial agonist	8.51	pIC50
estrone	Agonist	8.5	pKi
tibolone	Agonist	8.4	pEC50
R,R-THC	Agonist	8.38	pKi
compound 17b [PMID: 35286086]	Antagonist	8.34	pIC50
tamoxifen	Agonist	7.82	pKi
norendoxifen	Antagonist	7.77	pEC50
bazedoxifene	Antagonist	7.64	pIC50

Binding affinities (BindingDB)

5342 measured of 6036 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
MLS000083031	EC50	0.00114 nM
MLS000068778	EC50	0.00197 nM
CHEMBL1627420	EC50	0.004 nM
CHEMBL4591338	IC50	0.01 nM
3-((1R,3R)-1-(2,6-difluoro-4- (2-(3-(fluoromethyl)azetidin- 1-yl)ethoxy)phenyl)-3- methyl-1,3,4,9-tetrahydro- 2H-pyrido[3,4-b]indol-2-yl)- 2-fluoro-2-methylpropan-1-ol	EC50	0.01 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(1R,3R)-1-[2,6-difluoro-4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	EC50	0.014 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(R)-3-((1R,3R)-1-(2,6- difluoro-4-((1-(3- fluoropropyl)azetidin-3- yl)amino)phenyl)-7-fluoro-3- methyl-3,4-dihydro-1H- pyrido[3,4-b]indol-2(9H)-yl)- 2-fluoro-2-methylpropan-1-ol	EC50	0.018 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-7-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol	EC50	0.021 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(S)-3-((1R,3R)-1-(2,6- difluoro-4-((1-(3- fluoropropyl)azetidin-3- yl)amino)phenyl)-6-fluoro-3- methyl-1,3,4,9-tetrahydro- 2H-pyrido[3,4-b]indol-2-yl)- 2-fluoro-2-methylpropan-1-ol	EC50	0.021 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(R)-3-((1R,3R)-1-(2,6- difluoro-4-((1-(3- fluoropropyl)azetidin-3- yl)amino)phenyl)-5-fluoro-3- methyl-3,4-dihydro-1H- pyrido[3,4-b]indol-2(9H)-yl)- 2-fluoro-2-methylpropan-1-ol	EC50	0.023 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
CHEMBL4439408	IC50	0.024 nM
(1R,3R)-1-[2,6-difluoro-4-(1-propylazetidin-3-yl)oxyphenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	EC50	0.024 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-5-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol	EC50	0.024 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(8R,9S,14S,17R)-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol	KI	0.025 nM	US-9034854: Pharmaceutical composition comprising estetrol derivatives for use in cancer therapy
3-fluoro-N-[2-[3- (fluoromethyl)azetidin-1- yl]ethyl]-4-[(1R,3R)-2-(2- fluoro-2-methyl-propyl)-3- methyl-1,3,4,9- tetrahydropyrido[3,4-b]indol- 1-yl]aniline	EC50	0.025 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(S)-3-((1R,3R)-1-(2,6- difluoro-4-((1-(3- fluoropropyl)azetidin-3- yl)amino)phenyl)-3-methyl- 3,4-dihydro-1H-pyrido[3,4- b]indol-2(9H)-yl)-2-fluoro-2- (hydroxymethyl) propanenitrile	EC50	0.026 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(1R,3R)-1-[4-[2-[3-(difluoromethyl)azetidin-1-yl]ethoxy]-2,6-difluorophenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	EC50	0.027 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
estrogen	EC50	0.028 nM
US10399939, Example 132	EC50	0.029 nM	US-10399939: Tetrahydronaphthalene estrogen receptor modulators and uses thereof
CHEMBL4441471	IC50	0.03 nM
(1R,3R)-1-[4-[1-(3,3- dimethoxypropyl)azetidin-3- yl]oxy-2,6-difluoro-phenyl]- 2-(2-fluoro-2-methyl-propyl)- 3-methyl-1,3,4,9- tetrahydropyrido[3,4-b]indole	EC50	0.031 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(R)-3-((1R,3R)-1-(2,6- difluoro-4-(2-(3- (fluoromethyl)azetidin-1- yl)ethoxy)phenyl)-3-methyl- 3,4-dihydro-1H-pyrido[3,4- b]indol-2(9H)-yl)-2- (fluoromethyl)propan-1-ol	EC50	0.032 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(2S)-3-[(1R,3R)-1-[2,6-difluoro-4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol	EC50	0.033 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(S)-3-((1R,3R)-1-(2,6- difluoro-4-((2-(3- (fluoromethyl)azetidin-1- yl)ethyl)amino)phenyl)-3- methyl-1,3,4,9-tetrahydro- 2H-pyrido[3,4-b]indol-2-yl)- 2-fluoro-2-methylpropan-1-ol	EC50	0.033 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(R)-3-((1R,3R)-1-(2,6- difluoro-4-((1-(3- fluoropropyl)azetidin-3- yl)amino)phenyl)-3-methyl- 3,4-dihydro-1H-pyrido[3,4- b]indol-2(9H)-yl)-2-fluoro-2- (hydroxymethyl) propanenitrile	EC50	0.033 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
US10399939, Example 120	EC50	0.036 nM	US-10399939: Tetrahydronaphthalene estrogen receptor modulators and uses thereof
(4-methylbenzyl)-(tetrazolo[1,5-a]quinoxalin-4-yl)amine	EC50	0.0362 nM
US10399939, Example 124	EC50	0.037 nM	US-10399939: Tetrahydronaphthalene estrogen receptor modulators and uses thereof
US10399939, Example 134	EC50	0.038 nM	US-10399939: Tetrahydronaphthalene estrogen receptor modulators and uses thereof
US10399939, Example 105	EC50	0.04 nM	US-10399939: Tetrahydronaphthalene estrogen receptor modulators and uses thereof
CHEMBL4518283	IC50	0.04 nM
(1R,3R)-1-[2,6-difluoro-4-(1- methylazetidin-3-yl)oxy- phenyl]-2-(2-fluoro-2-methyl- propyl)-3-methyl-1,3,4,9- tetrahydropyrido[3,4-b]indole	EC50	0.041 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
1-((1R,3R)-1-(2,6- difluoro-4-(2-(3- (fluoromethyl)azetidin-1- yl)ethoxy)phenyl)-3- methyl-3,4-dihydro-1H- pyrido[3,4-b]indol-2(9H)- yl)-2-fluoro-2- methylpropan-1-one	EC50	0.043 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
CHEMBL4464224	IC50	0.045 nM
US10399939, Example 127	EC50	0.046 nM	US-10399939: Tetrahydronaphthalene estrogen receptor modulators and uses thereof
3’-Ethylamino-[1,1’;2’,1’’]terphenyl-4’-carbaldehyde oxime	KI	0.048 nM
(1R,3R)-2-(2,2- difluoroethyl)-1-[2,6- difluoro-4-[1-(3- fluoropropyl)azetidin-3- yl]oxy-phenyl]-3-methyl- 1,3,4,9-tetrahydropyrido[3,4- b]indole	EC50	0.048 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(1R,3R)-1-[2,6-difluoro-4-[1-(3-fluoropropyl)azetidin-3-yl]oxyphenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	EC50	0.049 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
2-(4-hydroxyphenyl)-3-{4-[2-(piperidin-1-yl)ethoxy]phenoxy}-1-benzothiophen-6-ol	IC50	0.05 nM
CHEMBL4455953	IC50	0.05 nM
(1R,3R)-1-[2,6-difluoro-4-[2-[(3R)-3-(fluoromethyl)pyrrolidin-1-yl]ethoxy]phenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	EC50	0.05 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
CHEMBL4753115	EC50	0.05 nM
CHEMBL4449709	IC50	0.051 nM
(1R,3R)-1-[4-(1- ethylazetidin-3-yl)oxy-2,6- difluoro-phenyl]-2-(2-fluoro- 2-methyl-propyl)-3-methyl- 1,3,4,9-tetrahydropyrido[3,4- b]indole	EC50	0.053 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(R)-3-((1R,3R)-1-(2,6- difluoro-4-((1-(3- fluoropropyl)azetidin-3- yl)amino)phenyl)-3-methyl- 1,3,4,9-tetrahydro-2H- pyrido[3,4-b]indol-2-yl)-2- fluoro-2-methylpropan-1-ol	EC50	0.053 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(R)-3-((1R,3R)-1-(2,6- difluoro-4-(2-(3- (fluoromethyl)azetidin-1- yl)ethoxy)phenyl)-3-methyl- 3,4-dihydro-1H-pyrido[3,4- b]indol-2(9H)-yl)-2- fluoropropan-1-ol	EC50	0.053 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
CHEMBL4437985	IC50	0.055 nM
(1R,3R)-2-(2-fluoro-2- methylpropyl)-1-(2- fluoro-4-(2-(3- (fluoromethyl)azetidin-1- yl)ethoxy)phenyl)-3- methyl-2,3,4,9- tetrahydro-1H-pyrido[3,4- b]indole	EC50	0.056 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
(1R,3R)-2-(2-fluoro-2- methylpropyl)-1-(2-fluoro-4- (2-(3-(fluoromethyl)azetidin- 1-yl)ethoxy)phenyl)-3- methyl-2,3,4,9-tetrahydro- 1H-pyrido[3,4-b]indole	EC50	0.056 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
N-(4-((1R,3R)-2-(2,2- difluoroethyl)-6-fluoro-3- methyl-2,3,4,9-tetrahydro- 1H-pyrido[3,4-b]indol-1-yl)- 3,5-difluorophenyl)-1-(3- fluoropropyl)azetidin-3- amine	EC50	0.056 nM	US-20250114338: TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.34	ED50	0.00456	nM	ESTRADIOL
11.00	EC50	0.01	nM	ESTRADIOL
11.00	IC50	0.01	nM	CHEMBL4591338
11.00	IC50	0.01	nM	ESTRADIOL
10.85	EC50	0.014	nM	CHEMBL5177342
10.82	Ki	0.015	nM	ACOLBIFENE
10.82	EC50	0.015	nM	CHEMBL149791
10.80	Ki	0.016	nM	CHEMBL308234
10.74	EC50	0.018	nM	ESTRADIOL
10.72	EC50	0.019	nM	ESTRADIOL
10.70	EC50	0.02	nM	ESTRADIOL
10.68	IC50	0.021	nM	CHEMBL4439408
10.64	Ki	0.023	nM	CHEMBL308234
10.62	IC50	0.024	nM	CHEMBL4439408
10.55	Ki	0.028	nM	CHEMBL291808
10.55	EC50	0.028	nM	ESTROGEN
10.54	EC50	0.029	nM	CHEMBL5787193
10.52	EC50	0.0301	nM	ESTRADIOL
10.52	Ki	0.03	nM	RALOXIFENE
10.52	EC50	0.03	nM	ESTRADIOL
10.52	IC50	0.03	nM	CHEMBL4447340
10.52	IC50	0.03	nM	CHEMBL4441471
10.51	IC50	0.031	nM	CHEMBL4649161
10.50	IC50	0.03162	nM	CHEMBL5400637
10.47	IC50	0.034	nM	CHEMBL5400637
10.44	EC50	0.036	nM	CHEMBL5756797
10.43	EC50	0.037	nM	CHEMBL5959890
10.42	EC50	0.038	nM	CHEMBL5948183
10.40	Ki	0.04	nM	CHEMBL2137046
10.40	IC50	0.04	nM	CHEMBL4518283
10.40	IC50	0.03981	nM	CHEMBL4743256
10.40	EC50	0.04	nM	CHEMBL5869147
10.38	Ki	0.042	nM	ACOLBIFENE
10.38	IC50	0.042	nM	CHEMBL5978181
10.35	IC50	0.045	nM	CHEMBL4464224
10.35	IC50	0.045	nM	CHEMBL5849595
10.34	IC50	0.046	nM	CHEMBL1193539
10.34	EC50	0.046	nM	CHEMBL5822315
10.34	EC50	0.046	nM	ESTRADIOL
10.33	Ki	0.047	nM	ACOLBIFENE
10.33	EC50	0.047	nM	ESTRADIOL
10.32	IC50	0.048	nM	CHEMBL4777139
10.30	IC50	0.05	nM	CHEMBL537254
10.30	IC50	0.05	nM	CHEMBL4455953
10.30	IC50	0.05012	nM	CHEMBL4777139
10.30	IC50	0.05	nM	GIREDESTRANT
10.30	IC50	0.05	nM	CHEMBL6009034
10.29	IC50	0.051	nM	CHEMBL4449709
10.28	IC50	0.053	nM	CHEMBL4649161
10.26	IC50	0.055	nM	CHEMBL4437985

PubChem BioAssay actives

2157 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[2-(4-chlorophenyl)-6-hydroxy-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone	1500307: Displacement of [3H]17beta-estradiol from ER in human MCF7 cells after 18 hrs by microbeta scintillation counting method	ic50	<0.0001	uM
[4-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone	1500307: Displacement of [3H]17beta-estradiol from ER in human MCF7 cells after 18 hrs by microbeta scintillation counting method	ic50	<0.0001	uM
(2S)-5-chloro-2-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-(4-fluorophenyl)-4-methyl-2H-chromen-6-ol	1591918: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by FITC/Hoechst 33342 staining based immunofluorescence imaging analysis	ic50	<0.0001	uM
(2S)-4-chloro-2-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-(3-hydroxyphenyl)-2H-chromen-6-ol	1591918: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by FITC/Hoechst 33342 staining based immunofluorescence imaging analysis	ic50	<0.0001	uM
(1R,3R)-1-[2,6-difluoro-4-[1-(3-fluoropropyl)azetidin-3-yl]oxyphenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	1658829: Induction of ERalpha degradation in human T47D cells	ic50	<0.0001	uM
19-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-8,18-dioxatetracyclo[9.8.0.02,7.012,17]nonadeca-1(11),2(7),3,5,12(17),13,15-heptaene-5,15-diol	1624901: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by Alexafluor-488 conjugate anti-mouse IgG antibody/Hoechst 33342 staining based immunofluorescence imaging analysis	ic50	<0.0001	uM
N-[4-[(6S,8R)-7-(2,2-difluoropropyl)-8-methyl-3,6,8,9-tetrahydropyrazolo[4,5-f]isoquinolin-6-yl]-3-methoxyphenyl]-1-(3-fluoropropyl)azetidin-3-amine	1681503: Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ER-alpha level incubated for 18 to 24 hrs by Alexa fluor 488/Hoechst staining based immunofluorescence imaging analysis	ic50	<0.0001	uM
2,2-difluoro-3-[(1R,3R)-1-[6-fluoro-3-[2-(3-fluoropropylamino)ethoxy]-2-methylphenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]propan-1-ol	2027451: Induction of ERalpha degradation in human MCF7 cells assessed as downregulation of ERaplha by multiplexed assay	ic50	<0.0001	uM
4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]phenol	1152694: Agonist activity at ER in human MCF7:WS8 cells assessed as increase in cell growth by measuring DNA level after 7 days by fluorescence analysis	ec50	0.0001	uM
Fulvestrant	1251781: Antagonist activity at ERalpha receptor in human MCF7 cells	ic50	0.0001	uM
(2R,3R,4S)-5-fluoro-3-(4-hydroxyphenyl)-4-methyl-2-[4-[(2S)-2-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-3,4-dihydro-2H-chromen-6-ol	248124: Inhibition of estrogen dependent human MCF-7 cell proliferation	ic50	0.0001	uM
1,3-diethyl-2-(4-hydroxyphenyl)-3H-inden-5-ol	254648: Transcriptional activation of estrogen receptor alpha in U2OS cell using estrogen-regulated luciferase reporter gene plasmid upon incubation for 20-30 mins at RT	ec50	0.0001	uM
(NE)-N-[(3,4-diphenylphenyl)methylidene]hydroxylamine	69873: Relative binding affinity for human estrogen receptor alpha compared to [3H]estradiol	ki	0.0001	uM
(2S)-2-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-(3-hydroxyphenyl)-4-methyl-2H-chromen-8-ol	1591918: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by FITC/Hoechst 33342 staining based immunofluorescence imaging analysis	ic50	0.0001	uM
3-[(1R,3R)-1-[2,6-difluoro-4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol	1768138: Antagonist activity at estrogen receptor in human T47D cells incubated for 18 hrs by ultra high sensitivity luminescence reporter gene assay	ic50	0.0001	uM
(1R,3R)-1-[2,6-difluoro-4-(1-propylazetidin-3-yl)oxyphenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	1658825: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by FITC/Hoechst staining based immunofluorescence imaging analysis	ic50	0.0001	uM
(1R,3R)-1-[4-[2-[3-(difluoromethyl)azetidin-1-yl]ethoxy]-2,6-difluorophenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	1658825: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by FITC/Hoechst staining based immunofluorescence imaging analysis	ic50	0.0001	uM
(1R,3R)-1-[2,6-difluoro-4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	1512607: Induction of ERalpha degradation in human MCF7 cells assessed as downregulation of ER alpha receptor expression measured after 18 to 22 hrs by immunofluorescence assay	ic50	0.0001	uM
3-[(1R,3R)-1-[2,6-difluoro-4-[1-(3-fluoropropyl)azetidin-3-yl]oxyphenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol	1768138: Antagonist activity at estrogen receptor in human T47D cells incubated for 18 hrs by ultra high sensitivity luminescence reporter gene assay	ic50	0.0001	uM
(1R,3R)-1-[2,6-difluoro-4-(1-prop-2-ynylazetidin-3-yl)oxyphenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	1658825: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by FITC/Hoechst staining based immunofluorescence imaging analysis	ic50	0.0001	uM
3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-7-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol	1768138: Antagonist activity at estrogen receptor in human T47D cells incubated for 18 hrs by ultra high sensitivity luminescence reporter gene assay	ic50	0.0001	uM
(1R,3R)-1-[2,6-difluoro-4-[2-[(3R)-3-(fluoromethyl)pyrrolidin-1-yl]ethoxy]phenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	1658825: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by FITC/Hoechst staining based immunofluorescence imaging analysis	ic50	0.0001	uM
3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-6-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol	1768138: Antagonist activity at estrogen receptor in human T47D cells incubated for 18 hrs by ultra high sensitivity luminescence reporter gene assay	ic50	0.0001	uM
3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol	1768138: Antagonist activity at estrogen receptor in human T47D cells incubated for 18 hrs by ultra high sensitivity luminescence reporter gene assay	ic50	0.0001	uM
3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-5-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol	1768138: Antagonist activity at estrogen receptor in human T47D cells incubated for 18 hrs by ultra high sensitivity luminescence reporter gene assay	ic50	0.0001	uM
(1R,3R)-1-[2,6-difluoro-4-(1-prop-2-enylazetidin-3-yl)oxyphenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole	1658825: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by FITC/Hoechst staining based immunofluorescence imaging analysis	ic50	0.0001	uM
(19R)-19-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-8,18-dioxatetracyclo[9.8.0.02,7.012,17]nonadeca-1(11),2(7),3,5,12(17),13,15-heptaene-5,15-diol	1624901: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by Alexafluor-488 conjugate anti-mouse IgG antibody/Hoechst 33342 staining based immunofluorescence imaging analysis	ic50	0.0001	uM
(19S)-19-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-8,18-dioxatetracyclo[9.8.0.02,7.012,17]nonadeca-1(11),2(7),3,5,12(17),13,15-heptaene-5,15-diol	1624901: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by Alexafluor-488 conjugate anti-mouse IgG antibody/Hoechst 33342 staining based immunofluorescence imaging analysis	ic50	0.0001	uM
19-[4-[2-[(3R)-3-(fluoromethyl)pyrrolidin-1-yl]ethoxy]phenyl]-8,18-dioxatetracyclo[9.8.0.02,7.012,17]nonadeca-1(11),2(7),3,5,12(17),13,15-heptaene-5,15-diol	1624901: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by Alexafluor-488 conjugate anti-mouse IgG antibody/Hoechst 33342 staining based immunofluorescence imaging analysis	ic50	0.0001	uM
19-[4-[(2S)-2-[(3R)-3-(fluoromethyl)pyrrolidin-1-yl]propoxy]phenyl]-8,18-dioxatetracyclo[9.8.0.02,7.012,17]nonadeca-1(11),2(7),3,5,12(17),13,15-heptaene-5,15-diol	1624901: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by Alexafluor-488 conjugate anti-mouse IgG antibody/Hoechst 33342 staining based immunofluorescence imaging analysis	ic50	0.0001	uM
[4-[2-(dodecylamino)ethoxy]phenyl]-[6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]methanone	1301304: Antagonist activity at ERalpha (unknown origin) transfected in 17beta-estradiol induced-HEK293 cells assessed as inhibition of estradiol-mediated protein transcriptional activity after 8 hrs by Luciferase reporter gene assay	ic50	0.0001	uM
(E)-3-[4-[[2-(4-chloro-2,6-dimethylbenzoyl)-6-hydroxy-1-benzothiophen-3-yl]oxy]phenyl]prop-2-enoic acid	1431903: Induction of ERalpha degradation in tamoxifen-sensitive human MCF7:WS8 cells after 24 hrs by CellTag 700 staining based In-cell western assay	ec50	0.0001	uM
(6S,8R)-6-[2,6-difluoro-4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-7-(2-fluoro-2-methylpropyl)-8-methyl-3,6,8,9-tetrahydropyrazolo[4,5-f]isoquinoline	1681503: Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ER-alpha level incubated for 18 to 24 hrs by Alexa fluor 488/Hoechst staining based immunofluorescence imaging analysis	ic50	0.0001	uM
(6S,8R)-7-[(1-fluorocyclopropyl)methyl]-6-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]-2-methoxyphenyl]-8-methyl-3,6,8,9-tetrahydropyrazolo[4,5-f]isoquinoline	1681503: Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ER-alpha level incubated for 18 to 24 hrs by Alexa fluor 488/Hoechst staining based immunofluorescence imaging analysis	ic50	0.0001	uM
3-[(1R,3R)-1-[2,6-difluoro-4-[2-(3-fluoropropylamino)ethoxy]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol	2027451: Induction of ERalpha degradation in human MCF7 cells assessed as downregulation of ERaplha by multiplexed assay	ic50	0.0001	uM
2,2-difluoro-3-[(1R,3R)-1-[4-[2-(3-fluoropropylamino)ethoxy]-2-methoxyphenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]propan-1-ol	2027451: Induction of ERalpha degradation in human MCF7 cells assessed as downregulation of ERaplha by multiplexed assay	ic50	0.0001	uM
N-[1-(3-fluoropropyl)azetidin-3-yl]-6-[(6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-3,6,8,9-tetrahydropyrazolo[4,5-f]isoquinolin-6-yl]pyridin-3-amine	1681460: Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ERalpha expression in presence of cycloheximide by Western blot analysis	ic50	0.0001	uM
N-[4-[(6S,8R)-7-(2,2-difluoroethyl)-8-methyl-3,6,8,9-tetrahydropyrazolo[4,5-f]isoquinolin-6-yl]-3-methoxyphenyl]-1-(3-fluoropropyl)azetidin-3-amine	1681503: Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ER-alpha level incubated for 18 to 24 hrs by Alexa fluor 488/Hoechst staining based immunofluorescence imaging analysis	ic50	0.0001	uM
1-(3-fluoropropyl)-N-[3-methoxy-4-[(6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-3,6,8,9-tetrahydropyrazolo[4,5-f]isoquinolin-6-yl]phenyl]azetidin-3-amine	1681503: Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ER-alpha level incubated for 18 to 24 hrs by Alexa fluor 488/Hoechst staining based immunofluorescence imaging analysis	ic50	0.0001	uM
2-fluoro-6-[(6S,8R)-1-fluoro-8-methyl-7-(2,2,2-trifluoroethyl)-2,6,8,9-tetrahydropyrazolo[4,3-f]isoquinolin-6-yl]-N-[1-(3-fluoropropyl)azetidin-3-yl]pyridin-3-amine	1726310: Induction of ERalpha degradation in human MCF7 cells incubated for 18 to 22 hrs by immuno-fluorescence assay	ic50	0.0001	uM
5-fluoro-N-[1-(3-fluoropropyl)azetidin-3-yl]-6-[(6S,8R)-8-methyl-7-(2,2,3-trifluoropropyl)-3,6,8,9-tetrahydropyrazolo[4,5-f]isoquinolin-6-yl]pyridin-3-amine	1726310: Induction of ERalpha degradation in human MCF7 cells incubated for 18 to 22 hrs by immuno-fluorescence assay	ic50	0.0001	uM
5-fluoro-6-[(6S,8R)-1-fluoro-8-methyl-7-(2,2,2-trifluoroethyl)-2,6,8,9-tetrahydropyrazolo[4,3-f]isoquinolin-6-yl]-N-[1-(3-fluoropropyl)azetidin-3-yl]pyridin-3-amine	1726310: Induction of ERalpha degradation in human MCF7 cells incubated for 18 to 22 hrs by immuno-fluorescence assay	ic50	0.0001	uM
1-[3,5-difluoro-4-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]azetidine-3-carboxamide	1810416: Induction of degradation of ERalpha in human MCF7 cells incubated for 4 hrs in presence of anti-ERalpha rabbit monoclonal antibodies measured after 4 hrs by immunofluorescent staining based assay	ec50	0.0001	uM
3-fluoro-N-[2-[4-fluoro-2-methyl-3-[(1R,3R)-3-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenoxy]ethyl]propan-1-amine	2027451: Induction of ERalpha degradation in human MCF7 cells assessed as downregulation of ERaplha by multiplexed assay	ic50	0.0001	uM
3-[(1R,3R)-1-[2,6-difluoro-3-[2-(3-fluoropropylamino)ethoxy]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol	2027451: Induction of ERalpha degradation in human MCF7 cells assessed as downregulation of ERaplha by multiplexed assay	ic50	0.0001	uM
4-[N-(2-chlorophenyl)-C-(4-hydroxyphenyl)carbonimidoyl]benzene-1,3-diol	1127140: Agonist activity at ERalpha (unknown origin) expressed in human HepG2 cells assessed as transcriptional activation after 24 hrs by ERE-luciferase reporter gene assay	ec50	0.0001	uM
(E)-3-[4-[2-adamantylidene-(4-hydroxyphenyl)methyl]phenyl]-N,N-bis(2-hydroxyethyl)prop-2-enamide	1446048: Displacement of [3H]estradiol from full-length human ERalpha receptor by scintillation counting	ki	0.0001	uM
4-[(E)-4-(4-hydroxyphenyl)-10-[methyl-[3-(4,4,5,5,5-pentafluoropentylsulfanyl)propyl]amino]dec-3-en-3-yl]phenol	248483: Inhibition of ER-MDA-MB 231 breast cancer cell proliferation over 200 hr	ic50	0.0002	uM
6-(4-fluorophenyl)-5-[4-(2-piperidin-1-ylethoxy)phenoxy]naphthalen-2-ol	290754: Displacement of [3H]estradiol from human recombinant ERalpha	ki	0.0002	uM
(E)-3-[4-[[2-[2-(1,1-difluoroethyl)-4-fluorophenyl]-6-hydroxy-1-benzothiophen-3-yl]oxy]phenyl]prop-2-enoic acid	1469719: Induction of selective estrogen receptor alpha degradation in human MCF7 cells after 18 to 24 hrs by in-cell Western analysis	ic50	0.0002	uM

CTD chemical–gene interactions

864 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases phosphorylation, affects reaction, affects cotreatment, increases response to substance, affects localization (+21 more)	426
bisphenol A	affects activity, affects localization, affects methylation, increases expression, increases degradation (+17 more)	172
Fulvestrant	increases reaction, affects folding, decreases activity, increases phosphorylation, increases response to substance (+14 more)	104
Tamoxifen	affects response to substance, increases response to substance, decreases activity, affects cotreatment, increases localization (+14 more)	95
Genistein	affects cotreatment, affects expression, affects binding, decreases reaction, decreases activity (+6 more)	67
afimoxifene	increases stability, affects activity, decreases activity, decreases response to substance, affects localization (+9 more)	50
Diethylstilbestrol	affects binding, decreases activity, affects cotreatment, affects response to substance, increases activity (+4 more)	50
Resveratrol	affects binding, increases expression, decreases activity, increases abundance, increases localization (+11 more)	34
Raloxifene Hydrochloride	affects localization, affects cotreatment, increases cleavage, affects activity, increases activity (+11 more)	33
daidzein	increases reaction, affects reaction, affects activity, affects binding, affects cotreatment (+5 more)	23
Coumestrol	affects binding, increases activity, increases reaction, affects cotreatment, increases expression (+4 more)	23
Methoxychlor	affects binding, increases expression, decreases reaction, increases activity, increases reaction (+4 more)	23
Tetrachlorodibenzodioxin	decreases expression, affects binding, increases reaction, affects cotreatment, increases expression (+7 more)	23
bisphenol S	increases phosphorylation, decreases abundance, affects cotreatment, affects binding, increases expression (+8 more)	22
Ethinyl Estradiol	affects binding, increases activity, decreases reaction, decreases expression, increases reaction (+1 more)	22
o,p’-DDT	decreases expression, increases activity, increases expression, increases reaction, decreases reaction (+3 more)	21
nonylphenol	decreases reaction, affects binding, increases reaction, affects activity, affects localization (+4 more)	21
bisphenol AF	increases activity, decreases reaction, decreases activity, increases expression, affects binding (+5 more)	20
Estrone	decreases reaction, increases response to substance, increases reaction, increases expression, affects binding (+1 more)	18
Zearalenone	affects response to substance, decreases reaction, increases reaction, decreases activity, increases expression (+4 more)	17
4-nonylphenol	affects binding, increases activity, affects cotreatment, increases expression, decreases reaction (+1 more)	16
DDT	affects cotreatment, increases expression, affects binding, increases activity, decreases expression	16
2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane	affects binding, increases activity, decreases reaction, increases reaction, increases expression	15
Diethylhexyl Phthalate	increases activity, decreases expression, increases reaction, decreases reaction, increases expression (+4 more)	15
4-tert-octylphenol	affects binding, increases activity, decreases reaction, increases reaction, increases expression	14
bisphenol B	affects activity, affects cotreatment, decreases reaction, affects localization, affects binding (+4 more)	14
Benzo(a)pyrene	affects cotreatment, decreases response to substance, decreases expression, affects binding, affects activity (+6 more)	14
Chlordecone	affects binding, increases activity, decreases reaction, increases expression	14
Dichlorodiphenyl Dichloroethylene	decreases expression, decreases reaction, increases expression, increases activity, affects binding (+1 more)	13
Endosulfan	decreases reaction, increases activity, affects binding, decreases expression, affects activity (+3 more)	13

ChEMBL screening assays

2435 unique, capped per target: 2037 binding, 363 functional, 35 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004750	Binding	Binding affinity to human ERalpha expressed in yeast relative to estradiol	Daucane phytoestrogens: a structure-activity study. — *J Nat Prod*
CHEMBL1010834	Functional	Antagonist activity at human ERalpha receptor expressed in HEC1 cells assessed as transcriptional activation after 24 hrs by luciferase reporter gene assay	Analogs of methyl-piperidinopyrazole (MPP): antiestrogens with estrogen receptor alpha selective activity. — *Bioorg Med Chem Lett*
CHEMBL1647191	ADMET	Antagonist activity at human ERalpha receptor expressed in human MCF7:D5L cells co-expressing ERE assessed as inhibition of estradiol-induced of luciferase gene expression at 1 uM after 18 hrs relative to ICI182780	New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription. — *Bioorg Med Chem*

Cellosaurus cell lines

46 cell lines: 25 cancer cell line, 6 embryonic stem cell, 5 induced pluripotent stem cell, 5 transformed cell line, 2 telomerase immortalized cell line, 1 conditionally immortalized cell line, 1 finite cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_2485	HeLa9903	Cancer cell line	Female
CVCL_3380	HeLa 422	Cancer cell line	Female
CVCL_3381	HeLa 432	Cancer cell line	Female
CVCL_3398	MCF7-422	Cancer cell line	Female
CVCL_3399	MCF7-432	Cancer cell line	Female
CVCL_3400	MCF7-488X1	Cancer cell line	Female
CVCL_3401	MCF7-490X1	Cancer cell line	Female
CVCL_4Y53	MCF-7:2A	Cancer cell line	Female
CVCL_A1K4	SEES3-1V human ESR1, clone1	Embryonic stem cell	Male
CVCL_A1K5	SEES3-1V human ESR1, clone2	Embryonic stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 94 trials:

NCT	Phase	Status	Title
NCT04234971	Phase 4	RECRUITING	Cost Effectiveness in Alveolar Bone Grafting in Patients With Cleft Lip and Palate
NCT04771156	Phase 4	RECRUITING	Ketorolac in Palatoplasty
NCT03766217	Phase 3	COMPLETED	Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
NCT06284434	Phase 3	UNKNOWN	Liposomal Bupivacaine Use in Alveolar Bone Graft Patients
NCT00930124	Phase 2	COMPLETED	Cleft Orthognathic Surgery Versus Distraction Osteogenesis - Which is Better?
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT00040222	Not specified	COMPLETED	Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer
NCT02557776	Not specified	COMPLETED	Written Genetic Counseling and Mutation Analysis of BRCA1 and BRCA2 to Patients With Breast Cancer
NCT03495544	Not specified	UNKNOWN	Study Estimating Association Between Germline Mutations and PD-L1 Expression in Breast Cancer
NCT03959267	Not specified	COMPLETED	Testing a Culturally Adapted Telephone Genetic Counseling Intervention
NCT04058418	Not specified	COMPLETED	Specialist Recommendation on FBC (Familial Breast Cancer) Chemoprevention Prescribing
NCT04125914	Not specified	ACTIVE_NOT_RECRUITING	Weight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families
NCT04169542	Not specified	RECRUITING	Impact of COVID-19 Pandemic on Out-of-Pocket Costs, Lost Wages, and Unemployment in Patients With Breast Cancer Undergoing Breast Surgery
NCT04197856	Not specified	UNKNOWN	Direct Information to At-risk Relatives
NCT07292246	Not specified	RECRUITING	A Prospective CohorT Study of HandX - Assisted ENdoscopic MAstectomy: Feasibility and Safety (ATHENA I Study)
NCT07307664	Not specified	RECRUITING	Increasing Germline Genetic Testing for Patients With Cancer
NCT06408337	Phase 1/2	RECRUITING	Phase I-IIa, to Evaluate the Safety, Feasibility, and Efficacy of the Use of BIOCLEFT in the Treatment of Cleft Palate.
NCT00070811	Not specified	COMPLETED	Assessing the Results of Lip Surgery in Patients With Cleft Lip and Palate
NCT00156442	Not specified	COMPLETED	A Study to Examine the Relationship Between Sleep Apnea and Cleft Lip/Palate
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01871623	Not specified	UNKNOWN	One-Piece Le Fort I Osteotomy Versus Segmental Le Fort I Osteotomy
NCT01932164	Not specified	COMPLETED	Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients
NCT02702869	Not specified	ENROLLING_BY_INVITATION	Allied Cleft & Craniofacial Quality-Improvement and Research Network (ACCQUIREnet)
NCT02789787	Not specified	COMPLETED	Clinical Effectiveness of Late Maxillary Protraction for Cleft Lip and Palate
NCT02845193	Not specified	COMPLETED	Effect of Novel Nasoalveolar Molding Techniques on Parents’ Satisfaction and Short Term Treatment Outcomes in Unilateral Cleft Lip and Palate Infants: A Randomized Controlled Trial
NCT02881606	Not specified	COMPLETED	Evaluation of the Clinical Effectiveness of Naso-alveolar Molding (NAM) Versus Computer Aided Design NAM (CAD/NAM) in Infants With Bilateral Cleft Lip and Palate: A Randomized Clinical Trial
NCT03011489	Not specified	UNKNOWN	Parent’s Satisfaction and Evaluation of Postsurgical Outcomes in Unilateral Cleft Lip / Palate Newly Born Infants With / Without Vacuum Formed Nasoalveolar Molding Aligners : A Controlled Clinical Trial
NCT03065686	Not specified	RECRUITING	Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing
NCT03165331	Not specified	UNKNOWN	Online Psychosocial Support for Young People With a Visible Difference: A Randomised Control Study
NCT03217890	Not specified	UNKNOWN	the Relationship Between Cleft Lip and / or Palate (Different Types) and ABO Blood Groups.
NCT03308266	Not specified	COMPLETED	Electromyographic Analysis of the Masticatory Muscles in Cleft Lip and Palate Children With Temporomandibular Disorders
NCT03395015	Not specified	COMPLETED	Efficacy of Maxillo-facial Treatment on Cleft Lip and Palate Patients Faces: Aesthetic Considerations
NCT03514563	Not specified	TERMINATED	Three Dimensional Facial Growth Analysis
NCT03563495	Not specified	COMPLETED	Tissue Engineered Constructs for Alveolar Cleft Repair
NCT03582111	Not specified	COMPLETED	Ultrasound Diagnosis of Cleft Lip and Palate
NCT03686761	Not specified	COMPLETED	Periodontal Changes Following Mid Maxillary Distraction
NCT03708406	Not specified	COMPLETED	Otologic and Rhinologic Outcomes in Children With Clef Palate
NCT03740841	Not specified	TERMINATED	Evaluation of the Effects of LUNII on Pre-operative Anxiety and on the Post-operative Period in Children With Cleft Lip and Palate Admitted for Alveolar Bone Graft: Pilot Study
NCT03750708	Not specified	WITHDRAWN	Oral Hygiene and Connected Toothbrush Before Alveolar Bone Graft for Cleft Lip and Palate
NCT03839290	Not specified	UNKNOWN	Development of the Palate in Bilateral Orofacial Cleft Newborns One Year After Early Neonatal Cheiloplasty
NCT03877666	Not specified	COMPLETED	Assessment of the Influence of Cleft Repair on Microcirculation of the Palate
NCT03976609	Not specified	COMPLETED	Three Dimensional Changes on Nasal Septum and Alveolar Cleft After Maxillary Expansion
NCT04108416	Not specified	COMPLETED	Unilateral Cleft Repair in One Surgery With Pure Primary Healing
NCT04236466	Not specified	UNKNOWN	Transverse Dento-skeletal Effects of Two Rapid Palatal Expansion Appliances in Cleft Lip and Palate Patients
NCT04331379	Not specified	COMPLETED	Effectiveness of Nasal-alar Elevator Combined With Taping Vs. Taping Alone on Improving the Nose Esthetics and Maxillary Arch Dimensions in Infants With Unilateral Complete Cleft Lip and Palate
NCT04331977	Not specified	COMPLETED	Effectiveness of Two Maxillary Expanders in Improving the Transverse Skeletal and Dental Dimensions in Patients With Cleft Lip and Palate
NCT04354116	Not specified	UNKNOWN	MARPE in Patients With Cleft Lip and Palate
NCT04369638	Not specified	TERMINATED	Fabrication of Naso-alveolar Molding (NAM) Appliance in Cleft Lip and Palate (CLP) From Digital Magnetic Resonance Imaging (MRI) Face Scan
NCT04381078	Not specified	UNKNOWN	Methods of Providing Information Prior to an Alveolar Bone Graft
NCT04384276	Not specified	COMPLETED	Weigh Easy: Simplifying Home Weight Monitoring for Infants
NCT04422847	Not specified	RECRUITING	Use of Computer Aided Design and 3D Printing for Anesthesiology Management in a Pediatric Patient With Cleft Facial Defect
NCT04422964	Not specified	UNKNOWN	Use of Computer Aided Design and 3D Printing for Anesthesiology Management in a Pediatric Patient With Cleft Facial Defect (3D Obturator) - Pilot Trial
NCT04455035	Not specified	TERMINATED	DynaCleft® Effects on Soft Tissues and on Quality of Life for Incomplete Unilateral Cleft Lip Infants
NCT04616690	Not specified	COMPLETED	Three-dimensional Cleft Lip and Palate Morphology Prior to One-stage Cleft Repair
NCT04619030	Not specified	UNKNOWN	Augmented Reality (AR): The Future of Patient Information Leaflets
NCT04696237	Not specified	COMPLETED	National Treatment Approach Versus Standardized Treatment Protocol to Manage Patients With Cleft Lip and Palate: a Cross Sectional Study
NCT04725370	Not specified	COMPLETED	Characterization of Cleft Lip and Palate Conditions in Guatemala
NCT04791813	Not specified	UNKNOWN	Assessment of Maxillary Arch Depth and Width in a Group of Surgically Repaired Unilateral Cleft Lip and Palate Children Versus Normal Children .
NCT04966572	Not specified	UNKNOWN	Short Term Efficiency of Presurgical Vacuum Formed Nasoalveolar Molding Aligners in Infants With Bilateral Cleft Lip and Palate Compared With Grayson Acrylic Formed Nasoalveolar Molding Appliances.
NCT04970095	Not specified	UNKNOWN	Alt-RAMEC Expansion and Protraction by EDO in Cleft Lip and Palate Patient

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ESR1 across ~30M SureChEMBL compounds — explore on Sugi Predict.