PRLR

Summary

PRLR (prolactin receptor, HGNC:9446) is a protein-coding gene on chromosome 5p13.2, encoding Prolactin receptor (P16471). This is a receptor for the anterior pituitary hormone prolactin (PRL).

This gene encodes a receptor for the anterior pituitary hormone, prolactin, and belongs to the type I cytokine receptor family. Prolactin-dependent signaling occurs as the result of ligand-induced dimerization of the prolactin receptor. Several alternatively spliced transcript variants encoding different membrane-bound and soluble isoforms have been described for this gene, which may function to modulate the endocrine and autocrine effects of prolactin in normal tissue and cancer.

Source: NCBI Gene 5618 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial hyperprolactinemia (Supportive, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 99 total — 3 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 20 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 16
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.44 (moderately constrained)
• MANE Select transcript: NM_000949
• Notable: 99 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9446
Approved symbol	PRLR
Name	prolactin receptor
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113494
Ensembl biotype	protein_coding
OMIM	176761
Entrez	5618

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000618457

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 10, TSL 2: 1, TSL 3: 3, TSL 4: 1, TSL 5: 5

ENST00000618457, ENST00000231423, ENST00000310101, ENST00000348262, ENST00000397391, ENST00000503330, ENST00000504500, ENST00000508107, ENST00000509140, ENST00000509839, ENST00000509934, ENST00000511486, ENST00000513753, ENST00000514088, ENST00000514206, ENST00000515839, ENST00000542609, ENST00000618625, ENST00000619676, ENST00000620785, ENST00000852369, ENST00000852370, ENST00000852371, ENST00000852372, ENST00000852373, ENST00000998606, ENST00001132364

RefSeq mRNA: 6 — MANE Select: NM_000949 NM_000949, NM_001204314, NM_001204315, NM_001204316, NM_001204317, NM_001204318

CCDS: CCDS3909, CCDS56358, CCDS56359, CCDS56360, CCDS56361, CCDS56362

Canonical transcript exons

ENST00000618457 — 10 exons

Exon	Start	End
ENSE00001209814	35089551	35089663
ENSE00001267139	35118061	35118122
ENSE00001793279	35086208	35086340
ENSE00003490130	35068216	35068285
ENSE00003506299	35068779	35068878
ENSE00003587122	35070124	35070265
ENSE00003607697	35072575	35072744
ENSE00003718395	35230268	35230487
ENSE00003742082	35084470	35084639
ENSE00003850479	35055702	35066102

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 92.39.

FANTOM5 (CAGE): breadth broad, TPM avg 3.3165 / max 230.3872, expressed in 493 samples.

Highest expression (Bgee): placenta, choroid plexus epithelium, seminal vesicle, endocervix, decidua.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRLR is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 21 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Caudate basal ganglia	eqtl	7.0e-19	+0.35	5:35202989:C:T
Brain Nucleus accumbens basal ganglia	eqtl	4.1e-17	+0.36	5:35222715:A:C
Cells EBV-transformed lymphocytes	eqtl	4.6e-12	+0.30	5:35312270:T:C
Esophagus Mucosa	eqtl	3.8e-09	+0.36	5:35465883:C:A
Brain Putamen basal ganglia	eqtl	9.3e-09	+0.32	5:35189522:A:G
Testis	eqtl	5.4e-07	+0.31	5:35168043:C:T
Adrenal Gland	eqtl	6.1e-07	-0.81	5:35247830:A:G
Skin Sun Exposed Lower leg	eqtl	1.2e-06	-0.27	5:35431533:T:C
Lung	eqtl	1.8e-04	+0.24	5:35239357:T:A
Artery Aorta	eqtl	3.6e-04	+0.99	5:35247855:T:C
Colon Transverse	eqtl	4.1e-04	-0.23	5:35195645:A:AC
Nerve Tibial	eqtl	7.5e-04	+0.18	5:35397256:A:C
Artery Tibial	eqtl	1.7e-03	+0.71	5:35228598:T:C
Prostate	eqtl	3.5e-03	+0.42	5:35474392:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.7e-03	-0.21	5:35431533:T:C
Stomach	eqtl	4.2e-03	-0.12	5:35237634:T:C
Liver	eqtl	2.1e-02	+0.19	5:35347260:C:A
Thyroid	eqtl	2.5e-02	+0.74	5:35267955:C:T
Adrenal Gland	sqtl	2.8e-02	-0.50	5:35449879:T:C
Adipose Subcutaneous	eqtl	3.9e-02	+0.22	5:35184256:G:A

FANTOM5 promoters

showing 10 of 16 alternative TSS:

Promoter ID	TPM avg	Samples expressed
61271	1.7771	341
61272	0.6139	214
61269	0.2880	127
61261	0.1217	13
61267	0.1015	19
61257	0.0940	44
61265	0.0814	38
61260	0.0574	12
61273	0.0506	22
61270	0.0457	15

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	92.39	gold quality
choroid plexus epithelium	UBERON:0003911	90.72	gold quality
seminal vesicle	UBERON:0000998	89.48	gold quality
endocervix	UBERON:0000458	85.03	gold quality
decidua	UBERON:0002450	83.02	gold quality
left adrenal gland	UBERON:0001234	82.90	gold quality
jejunal mucosa	UBERON:0000399	82.51	gold quality
right adrenal gland cortex	UBERON:0035827	82.45	gold quality
left adrenal gland cortex	UBERON:0035825	82.37	gold quality
right adrenal gland	UBERON:0001233	82.32	gold quality
adrenal cortex	UBERON:0001235	81.88	gold quality
ectocervix	UBERON:0012249	81.69	gold quality
body of uterus	UBERON:0009853	81.66	gold quality
endometrium	UBERON:0001295	81.47	gold quality
adrenal gland	UBERON:0002369	81.25	gold quality
uterus	UBERON:0000995	80.12	gold quality
mammary duct	UBERON:0001765	78.59	gold quality
adult mammalian kidney	UBERON:0000082	78.43	gold quality
myometrium	UBERON:0001296	78.33	gold quality
uterine cervix	UBERON:0000002	77.87	gold quality
epithelium of mammary gland	UBERON:0003244	77.51	gold quality
cauda epididymis	UBERON:0004360	77.07	gold quality
duodenum	UBERON:0002114	76.83	gold quality
rectum	UBERON:0001052	76.82	gold quality
corpus epididymis	UBERON:0004359	76.00	gold quality
kidney	UBERON:0002113	75.84	gold quality
thoracic mammary gland	UBERON:0005200	75.71	gold quality
mammary gland	UBERON:0001911	75.68	gold quality
liver	UBERON:0002107	75.59	gold quality
female reproductive system	UBERON:0000474	75.50	gold quality
ileal mucosa	UBERON:0000331	75.25	silver quality
mucosa of sigmoid colon	UBERON:0004993	75.19	gold quality
skin of hip	UBERON:0001554	74.95	gold quality
colonic mucosa	UBERON:0000317	73.97	gold quality
islet of Langerhans	UBERON:0000006	72.50	gold quality
jejunum	UBERON:0002115	72.37	gold quality
smooth muscle tissue	UBERON:0001135	72.21	gold quality
lower lobe of lung	UBERON:0008949	71.84	gold quality
pancreas	UBERON:0001264	71.78	gold quality
body of pancreas	UBERON:0001150	71.74	gold quality
pituitary gland	UBERON:0000007	71.56	gold quality
right lobe of liver	UBERON:0001114	71.47	gold quality
calcaneal tendon	UBERON:0003701	70.81	gold quality
periodontal ligament	UBERON:0008266	70.33	gold quality
vagina	UBERON:0000996	70.15	gold quality
diaphragm	UBERON:0001103	70.00	gold quality
adenohypophysis	UBERON:0002196	69.96	gold quality
mammalian vulva	UBERON:0000997	69.81	gold quality
adrenal tissue	UBERON:0018303	69.58	gold quality
sperm	CL:0000019	69.50	silver quality
upper leg skin	UBERON:0004262	68.75	gold quality
male germ cell	CL:0000015	68.00	silver quality
buccal mucosa cell	CL:0002336	67.88	gold quality
caput epididymis	UBERON:0004358	67.86	gold quality
oocyte	CL:0000023	67.80	gold quality
left ovary	UBERON:0002119	67.41	gold quality
monocyte	CL:0000576	67.08	gold quality
skin of abdomen	UBERON:0001416	67.06	gold quality
pancreatic ductal cell	CL:0002079	67.05	silver quality
cervix squamous epithelium	UBERON:0006922	66.98	gold quality
nephron tubule	UBERON:0001231	66.93	gold quality
small intestine	UBERON:0002108	66.92	gold quality
mononuclear cell	CL:0000842	66.72	gold quality
stomach	UBERON:0000945	66.70	gold quality
endothelial cell	CL:0000115	66.68	silver quality
mucosa of paranasal sinus	UBERON:0005030	66.56	silver quality
leukocyte	CL:0000738	66.41	gold quality
epithelial cell of pancreas	CL:0000083	66.34	silver quality
zone of skin	UBERON:0000014	66.29	gold quality
kidney epithelium	UBERON:0004819	66.04	gold quality
mucosa of transverse colon	UBERON:0004991	65.93	gold quality
tendon	UBERON:0000043	65.90	gold quality
ovary	UBERON:0000992	65.84	gold quality
cortex of kidney	UBERON:0001225	65.82	gold quality
skin of leg	UBERON:0001511	65.75	gold quality
right ovary	UBERON:0002118	65.67	gold quality
body of stomach	UBERON:0001161	65.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.18	gold quality
nipple	UBERON:0002030	64.90	silver quality
colonic epithelium	UBERON:0000397	64.79	gold quality
renal medulla	UBERON:0000362	64.69	gold quality
secondary oocyte	CL:0000655	64.35	gold quality
fallopian tube	UBERON:0003889	63.77	gold quality
metanephros	UBERON:0000081	63.55	gold quality
corpus callosum	UBERON:0002336	63.54	gold quality
oviduct epithelium	UBERON:0004804	63.50	silver quality
fundus of stomach	UBERON:0001160	63.48	gold quality
cartilage tissue	UBERON:0002418	63.37	silver quality
gall bladder	UBERON:0002110	63.08	gold quality
left uterine tube	UBERON:0001303	62.90	gold quality
nucleus accumbens	UBERON:0001882	62.90	gold quality
cervix epithelium	UBERON:0004801	62.54	gold quality
transverse colon	UBERON:0001157	62.48	gold quality
intestine	UBERON:0000160	62.37	gold quality
cerebellar vermis	UBERON:0004720	62.10	silver quality
vena cava	UBERON:0004087	61.97	gold quality
mucosa of urinary bladder	UBERON:0001259	61.85	gold quality
saphenous vein	UBERON:0007318	61.60	gold quality
gingiva	UBERON:0001828	61.21	silver quality
adult organism	UBERON:0007023	61.17	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	2077.26
E-CURD-119	yes	31.53
E-ANND-3	yes	14.40

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Choroid plexus	tissue	1734.0
Parathyroid gland	tissue	77.7
Placenta	tissue	47.2
Kidney	tissue	28.6
Nucleus accumbens	tissue	26.9
Breast	tissue	21.7
Endometrium 1	tissue	18.7
Cervix	tissue	18.2
Adrenal gland	tissue	11.5
Superior colliculi	tissue	11.1
Liver	tissue	10.2
Smooth muscle	tissue	10.1
Epididymis	tissue	8.8
Medulla oblongata	tissue	7.9
Seminal vesicle	tissue	7.7
Small intestine	tissue	7.6
Hypothalamus	tissue	7.0
Duodenum	tissue	6.2
Stomach 1	tissue	5.9
Locus coeruleus	tissue	5.8
Rectum	tissue	5.4
Colon	tissue	5.1
Pancreas	tissue	5.1
Vagina	tissue	4.6
Periaqueductal gray	tissue	4.3
Pituitary gland	tissue	4.0
Septum	tissue	3.7
Hippocampus	tissue	3.3
Thalamus	tissue	3.2
Skin 1	tissue	3.0
Pons	tissue	2.3
Substantia nigra	tissue	2.3
Caudate putamen	tissue	2.1
Fallopian tube	tissue	2.0
Midbrain	tissue	1.7
Postcentral gyrus	tissue	1.7
Ovary	tissue	1.6
Salivary gland	tissue	1.6
Amygdala	tissue	1.6
Spinal cord	tissue	1.5
Prostate	tissue	1.0
Bone marrow	tissue	1.0
Basal ganglia	tissue	0.9
Ventral forebrain	tissue	0.9
Gallbladder	tissue	0.8
Corpus callosum	tissue	0.8
Hippocampal formation	tissue	0.8
Esophagus	tissue	0.7
Tongue	tissue	0.7
Olfactory bulb	tissue	0.7
Cerebellum	tissue	0.6
Testis	tissue	0.5
Cerebral cortex	tissue	0.5
Adipose tissue	tissue	0.5
Putamen	tissue	0.5
Lung	tissue	0.5
Entorhinal cortex	tissue	0.5
Retrosplenial and cingulate cortex	tissue	0.5
Temporal cortex	tissue	0.5
Occipital cortex	tissue	0.5

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Ventromedial nucleus (89.5), Hippocampus, CA3 (60.5), Arcuate nucleus (54.6), Preoptic area (23.5), Corticomedial amygdala (21.1).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
FOXO3	Repression

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, ESR1, HOXA1, NR1I2, NR5A1, SP1, SP3, STAT5A, STAT5B

miRNA regulators (miRDB)

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

showing 30 of 438 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684

Functional genomics

gnomAD constraint: pLI 0.999, LOEUF 0.438, missense Z 1.66 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000618457 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:35,065,092–35,070,168	469 / 491.5	0.95	no
5:35,070,169–35,070,211	7 / 19.0	0.37	no
5:35,070,212–35,089,620	180 / 236.8	0.76	no

Literature-anchored findings (GeneRIF, showing 40)

• Review: Prolactin receptor signal transduction (PMID:11721697)
• results presented are consistent with a role of the PRL-PRLR system in bone/cartilage formation/repair processes (PMID:11997178)
• Genomic regions containing exons for human prolactin receptor, and 5’-flanking and intronic sequences, were determined and their order was established in chromosome 5p14-13. (PMID:12021177)
• Given its apparent widespread expression, this PRLr isoform may contribute to PRL action. (PMID:12351696)
• Plasma prolactin elevated in exercise and correlated with total prolactin-receptor expression per B lymphocyte. Increase in prolactin-receptor per B lymphocyte in response to exercise. Increased circulating B lymphocytes expressing prolactin receptor. (PMID:12391112)
• Results demonstrate a stimulatory effect of estradiol on the expression of human prolactin receptor mRNA species with alternative exons-1, hE1(3) and hE1(N1)in breast cancer cells. (PMID:12477494)
• To evaluate a possible role of prolactin receptor genes in SLE & MS formed an association study of PRLR SNPs was done. No statistically significant difference in the prolactin allele distribution was observed for any of the tested variations. (PMID:12559630)
• the interaction between Cyclophilin A and the PRLR plays a differential regulatory role in the various signaling pathways leading from the PRLR. (PMID:12668872)
• results demonstrate a direct effect of prolactin, via functional prolactin receptors, in reducing the lipoprotein lipase activity in human adipose tissue (PMID:12679477)
• prolactin signaling is attenuated by phosphorylation of the prolactin receptor on Thr391 (PMID:12819209)
• expression in hepatocytes was maximum in secondary liver cancer, high in obstructive jaundice, and less in cholelithiasis; expression in cholangiocytes was higher than in hepatocytes and was maximum during obstructive jaundice (PMID:12937675)
• data indicate that the prolactin receptor is a novel SCF(beta-TrCP) substrate and implicate beta-TrCP as an important negative regulator of prolactin signaling and cellular responses to this hormone (PMID:15082796)
• A150C (Leu–>Ile) transversion at exon 6 of PRLR was detected.Polymorphism of prolactin receptors might play a role in mammary carcinogenesis (PMID:15119991)
• transactivation occurs through an indirect interaction between erbB2 and prolactin or leptin receptors (PMID:15135067)
• Data support an “induced-fit” model for prolactin receptor binding where binding of the first receptor to human prolactin induces a conformation change in the hormone creating the second receptor-binding site. (PMID:15504038)
• Prolactin receptor mediates the Vav2 and Nek3 interaction. (PMID:15618286)
• Responsiveness of ovarian carcinomas to prolactin suggest that the prolactin/prolactin receptor system may be a new therapeutic target of ovarian carcinomas. (PMID:15700312)
• prolactin binding initiates limited proteasomal cleavage of its receptor, generating a cell-associated fragment containing the extracellular domain; findings described new potential mediator of prolactin action (PMID:16103113)
• phosphorylation of prolactin receptor on Ser349 is decreased in breast cancer cells lines and primary cancer tissue that exhibit stabilization and accumulation of prolactin receptor (PMID:16278670)
• Prolactin acts on the preformed Long Form homodimer to induce active signal transduction, while Short Form heterodimer lacks cytoplasmic sequences essential for activation. (PMID:16556730)
• a novel Estradiol-regulated non-estrogen responsive element-dependent transcriptional mechanism that mediates hPRLR expression (PMID:16651265)
• The data suggest that prolactin synergistically augments epidermal growth factor signaling in T47D breast cancer cells at least in part by lessening EGF-induced epidermal growth factor receptor downregulation. (PMID:16785991)
• An analysis of changes in the the expression of the prolactin receptor in liver fibrosis and liver cirrhosis. (PMID:17177141)
• The data revealed a widespread expresion of PRLR in normal and neoplastic human thyroid tissues. (PMID:17525486)
• residual agonism can be abolished either by further disrupting hormone site 2-receptor contacts by N-terminal deletion, as in Del1-9-G129R-human prolactin (hPRL), or by stabilizing hPRL and constraining its intrinsic flexibility, as in G129V-hPRL (PMID:17785459)
• In this comprehensive analysis covering 59 kb of the PRL locus and 210 kb of the PRLR locus, we found no significant association between common variation in these candidate genes and breast cancer risk or plasma PRL levels. (PMID:18053149)
• Results demonstrate that altered extracellular domain conformation, and not just a change in bulk, produces altered conformation of the intracellular signaling region of the receptors. (PMID:18081308)
• The resulting pattern of findings confirmed the hypotheses of the significance of the genes involved in the development of affiliative behaviors in the manifestation of ASD, the strongest results were obtained for allelic associations with the PRLR genes. (PMID:18207134)
• Prolactin promotes phosphorylation of PRLr on Ser349 and accelerates endocytosis of PRLr. Prolactin stimulated PRLr phosphorylation, endocytosis, and degradation in Jak2-null cells reconstituted with wild type Jak2. (PMID:18252943)
• GSK3 beta is a bona fide PRLr kinase that phosphorylates PRLr on Ser(349) and is required for the recognition of PRLr by beta Trcp, as well as for PRLr ubiquitination and degradation (PMID:18316598)
• The results of experiments using forced expression of ubiquitin mutants indicate that PRLr polyubiquitination via K63-linked chains is important for efficient interaction of PRLr with AP2 as well as for efficient internalization. (PMID:18573876)
• Mechanisms controlling PRLR isoform expression in the fallopian tube. (PMID:18596217)
• Prolactin receptor is significantly more expressed in male breast carcinoma than in gynaecomastia, and with different patterns of reactivity, suggesting a role for prolactin in male breast carcinogenesis. (PMID:18613925)
• Autocrine prolactin appears to act as an inducible survival factor in a clonogenic subpopulation of breast cancer cells (PMID:18681966)
• a heterozygous single nucleotide polymorphism in exon 6 of the PrlR gene, encoding Ile(146)–>Leu substitution in its extracellular domain confers constitutive activity to the receptor variant (PMID:18779591)
• Data indicate that src family kinases are key mediators of ligand-initiated prolactin receptor internalization, down-regulation, and signal transduction in breast cancer cells. (PMID:19056863)
• Even a very low level of PRLR expression was found to be sufficient to mediate PRL responsiveness in breast cancer cell lines. (PMID:19153125)
• Results suggest that the prolactin receptor conformation as stabilized by S-S bonds is required for the inhibitory action of S1b on prolactin-induced LF-mediated function and JAK2 association. (PMID:19273600)
• Human mammary epithelial cells harboring degradation-resistant PRLr display accelerated proliferation and increased invasive growth. (PMID:19276348)
• Increased expression of short form 1b prolactin receptor in prostate cancer cells decreases cell growth and cell migration and reduced invasive capacity. (PMID:19739126)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prlra	ENSDARG00000016570
danio_rerio	prlrb	ENSDARG00000045955
mus_musculus	Prlr	ENSMUSG00000005268
rattus_norvegicus	Prlr	ENSRNOG00000057557

Paralogs (23): CRLF1 (ENSG00000006016), IL12RB2 (ENSG00000081985), IL5RA (ENSG00000091181), IL12RB1 (ENSG00000096996), IL27RA (ENSG00000104998), EBI3 (ENSG00000105246), GHR (ENSG00000112964), LIFR (ENSG00000113594), LEPR (ENSG00000116678), CSF3R (ENSG00000119535), CNTFR (ENSG00000122756), IL13RA2 (ENSG00000123496), IL13RA1 (ENSG00000131724), IL6ST (ENSG00000134352), IL11RA (ENSG00000137070), OSMR (ENSG00000145623), IL2RG (ENSG00000147168), IL6R (ENSG00000160712), IL23R (ENSG00000162594), IL31RA (ENSG00000164509), IL3RA (ENSG00000185291), CSF2RA (ENSG00000198223), CRLF2 (ENSG00000205755)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97763) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 49 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal mammary gland development	2
decreased body weight	2
abnormal pup retrieval	2
reduced male fertility	2
male infertility	2
slow postnatal weight gain	2
delayed bone ossification	1
decreased bone mineral density	1
abnormal coat/ hair morphology	1
abnormal hair cycle	1
abnormal thyroid gland morphology	1
abnormal prostate gland epithelium morphology	1
abnormal lacrimal gland morphology	1
abnormal maternal nurturing	1
abnormal circulating calcium level	1
abnormal lactation	1
abnormal reproductive system physiology	1
female infertility	1
abnormal oogenesis	1
coarse hair	1
abnormal bone mineralization	1
increased circulating parathyroid hormone level	1
decreased insulin secretion	1
decreased ovulation rate	1
abnormal decidualization	1

+24 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
Bos taurus	O46600	99.1%	Diamond
Bos indicus	P79108	99.1%	Diamond
Macaca mulatta	P79194	98.6%	Diamond
Papio anubis	Q9XSZ1	98.6%	Diamond
Ovis aries	Q28575	97.5%	Diamond
Ailuropoda melanoleuca	Q95JF2	93.6%	Diamond
Canis lupus familiaris	Q9TU69	93.6%	Diamond
Cervus elaphus	Q28235	91.0%	Diamond
Saimiri boliviensis boliviensis	Q95ML5	90.9%	Diamond
Sus scrofa	P19756	90.8%	Diamond
Gallus gallus	Q02092	90.5%	Diamond
Columba livia	Q90375	90.5%	Diamond
Meleagris gallopavo	Q91094	90.0%	Diamond
Oryctolagus cuniculus	P19941	88.7%	Diamond
Cavia porcellus	Q9JI97	76.0%	Diamond
Oreochromis niloticus	Q91513	52.7%	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
IL7R	protein-coding	3575
SPEF2	protein-coding	79925
DNAJC21-AS1	ncRNA	124900961
DNAJC21	protein-coding	134218
AGXT2	protein-coding	64902
TTC23L	protein-coding	153657
BRIX1	protein-coding	55299
RAD1	protein-coding	5810
CAPSL	protein-coding	133690

Protein

Protein identifiers

Prolactin receptor — P16471 (reviewed: P16471)

All UniProt accessions (8): P16471, D6R9E1, D6R9P5, D6R9V7, D6RAN9, D6RC67, D6RD41, D6RJC8

UniProt curated annotations — full annotation on UniProt →

Function. This is a receptor for the anterior pituitary hormone prolactin (PRL). Acts as a prosurvival factor for spermatozoa by inhibiting sperm capacitation through suppression of SRC kinase activation and stimulation of AKT. Isoform 4 is unable to transduce prolactin signaling. Isoform 6 is unable to transduce prolactin signaling.

Subunit / interactions. Homodimer upon hormone binding. Interacts with SMARCA1. Interacts with GH1. Interacts with CSH. Interacts with NEK3 and VAV2 and this interaction is prolactin-dependent.

Subcellular location. Membrane Secreted.

Tissue specificity. Expressed in breast, placenta, kidney, liver and pancreas.

Disease relevance. Multiple fibroadenomas of the breast (MFAB) [MIM:615554] A benign breast disease marked by lobuloalveolar growth with abnormally high proliferation of the epithelium, and characterized by the presence of more than 3 fibroadenomas in one breast. Fibroadenomas are adenomas containing fibrous tissue. The disease is caused by variants affecting the gene represented in this entry. Hyperprolactinemia (HPRL) [MIM:615555] A disorder characterized by increased levels of prolactin in the blood not associated with gestation or the puerperium. HPRL may result in infertility, hypogonadism, and galactorrhea. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. The box 1 motif is required for JAK interaction and/or activation.

Miscellaneous. Soluble isoform that appears specific for the BT-474 breast cancer cell line. Includes exon 11. Does not transduce prolactin signaling. Produced by deletion of part of exon 10 and frameshift. Does not transduce prolactin signaling. Splices from exon 7 to exon 11. SF1b with deletion of exon 4. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the type I cytokine receptor family. Type 1 subfamily.

Isoforms (9)

UniProt ID	Names	Canonical?
P16471-1	1	yes
P16471-2	2, Delta-S1
P16471-3	3
P16471-4	4, SF1a, Short form 1a
P16471-5	5, Intermediate
P16471-6	6, SF1b, Short form 1b
P16471-7	7, Delta 7/11
P16471-8	8, Delta 4-SF1b
P16471-9	9, SF1c, Short form 1c

RefSeq proteins (6): NP_000940, NP_001191243, NP_001191244, NP_001191245, NP_001191246, NP_001191247 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003528	Long_hematopoietin_rcpt_CS	Conserved_site
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015152	Growth/epo_recpt_lig-bind	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR050379	Type-I_Cytokine_Rcpt	Family

Pfam: PF09067

UniProt features (67 total): strand 20, splice variant 14, helix 8, glycosylation site 3, sequence variant 3, region of interest 3, short sequence motif 2, binding site 2, disulfide bond 2, topological domain 2, turn 2, domain 2, signal peptide 1, chain 1, compositionally biased region 1, transmembrane region 1

Structure

Experimental structures (PDB)

12 structures by resolution:

PDB	Title	Method	Resolution (Å)
3N06	A mutant human Prolactin receptor antagonist H27A in complex with the extracellular …	X-RAY DIFFRACTION	2
3NCE	A mutant human Prolactin receptor antagonist H27A in complex with the mutant …	X-RAY DIFFRACTION	2
3MZG	Crystal structure of a human prolactin receptor antagonist in complex with the …	X-RAY DIFFRACTION	2.1
3N0P	A mutant human Prolactin receptor antagonist H30A in complex with the extracellular …	X-RAY DIFFRACTION	2.1
3NCB	A mutant human Prolactin receptor antagonist H180A in complex with the extracellular …	X-RAY DIFFRACTION	2.1
3D48	Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of …	X-RAY DIFFRACTION	2.5
3NCC	A human Prolactin receptor antagonist in complex with the mutant extracellular domain …	X-RAY DIFFRACTION	2.5
3NCF	A mutant human Prolactin receptor antagonist H30A in complex with the mutant …	X-RAY DIFFRACTION	2.8
1BP3	THE XRAY STRUCTURE OF A GROWTH HORMONE-PROLACTIN RECEPTOR COMPLEX	X-RAY DIFFRACTION	2.9
4I18	Crystal structure of human prolactin receptor complexed with Fab fragment	X-RAY DIFFRACTION	3.24
2LFG	Solution structure of the human prolactin receptor ecd domain d2	SOLUTION NMR
2N7I	NMR structure of the prolactin receptor transmembrane domain	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16471-F1	61.67	0.30

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 4I18

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, FDA approved drug targets, Biotech drugs, Human disease related genes

Protein evidence: Evidence at protein level

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 (2)

Position	Role
211	Zn(2+)
212	Zn(2+)

Disulfide bonds (2)

Type	Positions
Disulfide bond	36–46, 75–86

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	59, 104, 233

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-982772	Growth hormone receptor signaling	curated
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-168256	Immune System	—
R-HSA-1170546	Prolactin receptor signaling	electronic

MSigDB gene sets: 395 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOZGIT_ESR1_TARGETS_DN, GOBP_MAMMARY_GLAND_EPITHELIUM_DEVELOPMENT, GOBP_GROWTH, GOCC_CELL_SURFACE, GOBP_B_CELL_PROLIFERATION, GOBP_MAMMARY_GLAND_EPITHELIAL_CELL_DIFFERENTIATION

GO Biological Process (12): steroid biosynthetic process (GO:0006694), activation of transmembrane receptor protein tyrosine kinase activity (GO:0007171), embryo implantation (GO:0007566), lactation (GO:0007595), positive regulation of cell population proliferation (GO:0008284), cytokine-mediated signaling pathway (GO:0019221), positive regulation of B cell proliferation (GO:0030890), activation of Janus kinase activity (GO:0042976), negative regulation of apoptotic process (GO:0043066), cellular response to granulocyte macrophage colony-stimulating factor stimulus (GO:0097011), positive regulation of cold-induced thermogenesis (GO:0120162), prolactin signaling pathway (GO:0038161)

GO Molecular Function (8): prolactin receptor activity (GO:0004925), lipid binding (GO:0008289), peptide hormone binding (GO:0017046), protein kinase binding (GO:0019901), cytokine binding (GO:0019955), metal ion binding (GO:0046872), cytokine receptor activity (GO:0004896), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), endosome lumen (GO:0031904), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Cytokine Signaling in Immune system	2
Immune System	1

GO top-level categories

50 GO namespaces:

Category	Terms
cellular anatomical structure	3
activation of protein kinase activity	2
cellular response to cytokine stimulus	2
cytokine-mediated signaling pathway	2
binding	2
steroid metabolic process	1
lipid biosynthetic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
protein-containing complex assembly	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor signaling pathway	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
peptidyl-tyrosine phosphorylation	1
positive regulation of receptor signaling pathway via JAK-STAT	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
response to granulocyte macrophage colony-stimulating factor	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
hormone-mediated signaling pathway	1
cytokine receptor activity	1
prolactin signaling pathway	1
hormone binding	1
kinase binding	1
protein binding	1
cation binding	1
transmembrane signaling receptor activity	1
cytokine binding	1
immune receptor activity	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
endosome	1
intracellular organelle lumen	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
activation of Janus kinase activity	BP	direct assay
activation of transmembrane receptor protein tyrosine kinase activity	BP	direct assay
negative regulation of apoptotic process	BP	direct assay
cell surface	CC	direct assay
lipid binding	MF	physical interaction
peptide hormone binding	MF	physical interaction
prolactin receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 826 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRLR	PRL	P01236	959
PRLR	CSN2	P05814	784
PRLR	STAT5A	P42229	783
PRLR	STAT5B	P51692	778
PRLR	CSH1	P01243	755
PRLR	CSH1	P01243	752
PRLR	JAK2	O60674	739
PRLR	SRR	Q9GZT4	710
PRLR	PGR	P06401	663
PRLR	HSD17B7	P56937	624
PRLR	SOCS2	O14508	582
PRLR	SPEF2	Q9C093	580
PRLR	ESR1	P03372	577
PRLR	FSHR	P23945	574
PRLR	OXTR	P30559	572

IntAct

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

6 partners by confidence:

Partner	Interaction type	MIscore	Records
INSIG2	physical association	0.560	3
PLPP6	physical association	0.560	3
YWHAZ	physical association	0.400	3
H1-1	physical association	0.400	1
NEK3	physical association	0.400	1
VAV2	physical association	0.400	1

BioGRID (30 interactions; top human partners by supporting records): CREBBP (Affinity Capture-Western; 3 records), FBXW11 (Affinity Capture-Western; 3 records), TEC (Affinity Capture-Western; 3 records), VAV1 (Reconstituted Complex; 3 records), JAK2 (Affinity Capture-Western; 2 records), PPIA (Affinity Capture-Western; 2 records), BTRC (Affinity Capture-Western), GTF3A (Affinity Capture-Western), HIST1H1A (Cross-Linking-MS (XL-MS)), INSIG2 (Two-hybrid), KIAA1429 (Affinity Capture-RNA), PPAPDC2 (Two-hybrid), PTPN11 (Affinity Capture-Western), SOCS2 (Affinity Capture-Western), SOCS3 (Affinity Capture-Western)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
GH1	up-regulates	PRLR	binding
PRL	up-regulates	PRLR	binding
PRLR	“down-regulates quantity by repression”	FOXO3	“transcriptional regulation”

Protein complexes (CORUM) (1)

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

1 complexes by size:

Complex	Subunits	Members
★ GHR-PRLR complex	2	GHR, PRLR

Ligand–receptor pairs (CellPhoneDB) (1)

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

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
PRL	receptor	Signaling by Prolactin

Disease & clinical

Genetic variants

Variant evidence for PRLR: 99 ClinVar records (4 pathogenic / likely pathogenic); 10 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	68
Likely benign	13
Benign	3

Top pathogenic / likely-pathogenic (4)

Showing all 4 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
929748	NM_000949.7(PRLR):c.851T>G (p.Leu284Trp)	Likely pathogenic	criteria provided, single submitter	1
89027	NM_000949.7(PRLR):c.635A>G (p.His212Arg)	Pathogenic	no assertion criteria provided	1
599315	NM_000949.7(PRLR):c.511C>T (p.Arg171Ter)	Pathogenic	no assertion criteria provided	1
599316	NM_000949.7(PRLR):c.806C>T (p.Pro269Leu)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PRLR’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; 33 predictions of 1,432):

Position(s)	Effect	Δscore	Sites
5:35066103–35066104	acceptor_loss	1.0000	3
5:35070122–35070123	donor_loss	1.0000	5
5:35070267	acceptor_loss	1.0000	3
5:35070271	acceptor_gain	1.0000
5:35072573–35072574	donor_loss	1.0000	5
5:35084468–35084469	donor_loss	1.0000	5
5:35089549–35089550	donor_loss	1.0000	5
5:35230267	donor_loss	1.0000	2
5:35066103–35066104	acceptor_loss	0.9900	3
5:35066106	acceptor_gain	0.9900

AlphaMissense

663 missense substitutions predicted likely pathogenic (of 4,099 scored), across 188 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
F88	8	0.965	0.997
F44	8	0.945	0.995
D120	8	0.921	0.963
C86	7	0.994	0.998
W48	7	0.990	1.000
C46	7	0.988	0.995
C36	7	0.986	0.997
C75	7	0.986	0.997
W151	7	0.977	0.997
W218	7	0.960	0.993
W96	7	0.947	0.995
S216	7	0.941	0.994
W215	7	0.935	0.989
N107	7	0.930	0.992
W163	7	0.927	0.986
W180	7	0.915	0.988
D77	7	0.905	0.934
W47	7	0.866	0.981
C208	7	0.837	0.992
D211	7	0.814	0.889

HPA cancer prognostics

RNA cancer specificity: Group enriched (Breast Invasive Carcinoma, Kidney Chromophobe)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	favorable	0.000701

Disease associations

OMIM: gene MIM:176761 | disease phenotypes: MIM:615555

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
familial hyperprolactinemia	Supportive	Autosomal dominant	2

Mondo (2): familial hyperprolactinemia (MONDO:0014250), primary ovarian failure (MONDO:0005387)

Orphanet (2): Familial hyperprolactinemia (Orphanet:397685), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

16 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000134	Female hypogonadism
HP:0000141	Amenorrhea
HP:0000789	Infertility
HP:0000870	Increased circulating prolactin concentration
HP:0000876	Oligomenorrhea
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0008222	Female infertility
HP:0010619	Fibroadenoma of the breast
HP:0011462	Young adult onset
HP:0012886	Hemorrhagic ovarian cyst
HP:0031109	Agalactia
HP:0100829	Galactorrhea

GWAS associations

10 associations:

Study	Trait	p-value
GCST009391_1512	Metabolite levels	6e-83
GCST90000025_810	Appendicular lean mass	1e-13
GCST007576_73	Chronotype	2e-9
GCST003219_43	Advanced age-related macular degeneration	2e-8
GCST008895_2	Psychotic experience	3e-8
GCST90093090_2	DHEAS levels	2e-7
GCST004251_4	Paneth cell defects in Crohn’s disease	2e-6
GCST006248_11	Response to lurasidone in schizophrenia	8e-6
GCST009391_1814	Metabolite levels	8e-6
GCST009391_740	Metabolite levels	9e-6

EFO canonical traits (from GWAS)

9 canonical traits:

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0007963	abnormal paneth cell measurement
EFO:0008328	chronotype measurement
EFO:0005940	psychotic symptoms
EFO:0010464	beta-aminoisobutyric acid measurement
EFO:0010343	cholesteryl ester 18:0 measurement
EFO:0010391	sphingomyelin 16:0 measurement
EFO:0004980	appendicular lean mass
EFO:0007001	dehydroepiandrosterone sulphate measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5588 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Prolactin receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
prolactin	Agonist	8.05	pKd

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Cyclo(ARYQSRVE)	KD	2000 nM
Cyclo(ALYSYRVE)	KD	3000 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.70	Kd	2000	nM	CHEMBL504608
5.52	Kd	3000	nM	CHEMBL486199

PubChem BioAssay actives

2 with measured affinity, of 3 total; 2 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
3-[(2S,5S,8S,11S,14S,17S,20S,23S)-14-(3-amino-3-oxopropyl)-8,20-bis[3-(diaminomethylideneamino)propyl]-17-(hydroxymethyl)-11-[(4-hydroxyphenyl)methyl]-5-methyl-3,6,9,12,15,18,21,24-octaoxo-23-propan-2-yl-1,4,7,10,13,16,19,22-octazacyclotetracos-2-yl]propanoic acid	366992: Binding affinity to human prolactin receptor extracellular binding domain by surface plasmon response	kd	2.0000	uM
3-[(2S,5R,8R,11S,14S,17S,20S,23S)-20-[3-(diaminomethylideneamino)propyl]-14-(hydroxymethyl)-11,17-bis[(4-hydroxyphenyl)methyl]-5-methyl-8-(2-methylpropyl)-3,6,9,12,15,18,21,24-octaoxo-23-propan-2-yl-1,4,7,10,13,16,19,22-octazacyclotetracos-2-yl]propanoic acid	366992: Binding affinity to human prolactin receptor extracellular binding domain by surface plasmon response	kd	3.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, affects cotreatment, decreases expression	7
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	3
Progesterone	affects cotreatment, decreases expression, increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression	2
Formaldehyde	increases expression	2
Testosterone	increases expression	2
Particulate Matter	decreases expression, increases abundance	2
methyleugenol	decreases expression	1
bisphenol A	increases expression	1
arsenite	increases methylation	1
methylparaben	increases expression	1
o,p’-DDT	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
latrunculin A	decreases uptake	1
butylparaben	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
glycidamide	decreases expression	1
chromium hexavalent ion	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
azaspiracid	decreases uptake	1
clothianidin	decreases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
Acetaminophen	decreases expression	1
Glyphosate	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL980832	Binding	Binding affinity to human prolactin receptor extracellular binding domain by surface plasmon response	Synthesis and screening of a cyclic peptide library: discovery of small-molecule ligands against human prolactin receptor. — *Bioorg Med Chem*

Cellosaurus cell lines

7 cell lines: 3 transformed cell line, 2 cancer cell line, 1 spontaneously immortalized cell line, 1 factor-dependent cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E6RI	Genomeditech CHO-K1 H_PRLR	Spontaneously immortalized cell line	Female
CVCL_E7I6	HEK293 HL5	Transformed cell line	Female
CVCL_E7I7	HEK293 HL10	Transformed cell line	Female
CVCL_E7I8	HEK293 HL21	Transformed cell line	Female
CVCL_E7I9	Ba/F3-LP	Factor-dependent cell line
CVCL_TH10	HAP1 PRLR (-) 1	Cancer cell line	Male
CVCL_TH11	HAP1 PRLR (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00541554	Phase 4	UNKNOWN	Reversal of Antipsychotic-Induced Hyperprolactinemia, Weight Gain, Hyperglycemia and Dyslipidemia
NCT00625950	Phase 4	COMPLETED	Endometriosis Patients Undergoing Quinagolide Treatment
NCT00889512	Phase 4	TERMINATED	The Luveris In Vitro Fertilization Trial
NCT01085383	Phase 4	COMPLETED	Aripiprazole and Prolactin Study
NCT01742390	Phase 4	UNKNOWN	A Multicenter Study to Evaluate the Effects of Switching to Aripiprazole 12 Weeks on the Sexual Dysfunction From Risperidone or Paliperidone in Patients With Schizophrenia Spectrum Disorders or Bipolar Spectrum Disorders
NCT00000374	Phase 4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	Phase 4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	Phase 4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	Phase 4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	Phase 4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	Phase 4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	Phase 4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	Phase 4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	Phase 4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	Phase 4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	Phase 4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	Phase 4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	Phase 4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	Phase 4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	Phase 4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	Phase 4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	Phase 4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	Phase 4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	Phase 4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	Phase 4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	Phase 4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	Phase 4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	Phase 4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	Phase 4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	Phase 4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	Phase 4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	Phase 4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	Phase 4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	Phase 4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	Phase 4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	Phase 4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	Phase 4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	Phase 4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	Phase 4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	Phase 4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	Phase 4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	Phase 4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	Phase 4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	Phase 4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	Phase 4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety
NCT00177580	Phase 4	COMPLETED	Improving Symptoms of Schizophrenia and Schizoaffective Disorder by Supplementing Medications With Pravastatin
NCT00182442	Phase 4	COMPLETED	Cognition, Functioning and Quality of Life
NCT00182494	Phase 4	UNKNOWN	Diabetes Prevention Program in Schizophrenia [DPPS]
NCT00183625	Phase 4	COMPLETED	Supported Employment and Skills Training in Conjunction With Pharmacotherapy in Schizophrenia Patients
NCT00186771	Phase 4	UNKNOWN	Magnetic Stimulation as a Treatment for Auditory Hallucinations in Schizophrenia
NCT00190749	Phase 4	COMPLETED	Safety Study of Olanzapine and a Comparator in Patients With Schizophrenia and Schizoaffective Disorder
NCT00191555	Phase 4	COMPLETED	Efficacy Study of Switching Stabilized Schizophrenic Patients From Conventional to Atypical Antipsychotic Treatment
NCT00194025	Phase 4	COMPLETED	Valproate in Late Life Schizophrenia
NCT00199940	Phase 4	COMPLETED	Safety And Efficacy Study Of Ziprasidone In Pediatric Psychotic Illness
NCT00202306	Phase 4	COMPLETED	Indicated Prevention of Psychotic Disorders With Low-dose Lithium
NCT00203788	Phase 4	COMPLETED	Improving Work Outcome in People With Recent-onset Schizophrenia
NCT00204061	Phase 4	COMPLETED	Early Pharmacological and Psychological Intervention for Late Prodromal States of Psychosis
NCT00205660	Phase 4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00206102	Phase 4	COMPLETED	A Study of the Cataractogenic Potential of Seroquel and Risperdal in the Treatment of Participants With Schizophrenia or Schizoaffective Disorder
NCT00208143	Phase 4	COMPLETED	Seroquel Therapy for Substance Use Disorders Comorbid With Schizophrenia