NANOS3

Summary

NANOS3 (nanos C2HC-type zinc finger 3, HGNC:22048) is a protein-coding gene on chromosome 19p13.12, encoding Nanos homolog 3 (P60323). Plays a role in the maintenance of the undifferentiated state of germ cells regulating the spermatogonia cell cycle and inducing a prolonged transit in G1 phase.

Enables enzyme activator activity. Involved in germ cell development; mRNA destabilization; and negative regulation of translation. Located in cytosol; nucleoplasm; and perinuclear region of cytoplasm.

Source: NCBI Gene 342977 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ovarian failure (Moderate, GenCC)
• GWAS associations: 33
• Clinical variants (ClinVar): 221 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001098622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22048
Approved symbol	NANOS3
Name	nanos C2HC-type zinc finger 3
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	NANOS1L, NOS3
Ensembl gene	ENSG00000187556
Ensembl biotype	protein_coding
OMIM	608229
Entrez	342977

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000339133, ENST00000397555, ENST00000591161, ENST00000591727

RefSeq mRNA: 1 — MANE Select: NM_001098622 NM_001098622

CCDS: CCDS42511

Canonical transcript exons

ENST00000339133 — 2 exons

Exon	Start	End
ENSE00001369175	13877134	13877765
ENSE00002874727	13880442	13880757

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 95.00.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9962 / max 44.5571, expressed in 380 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174194	0.6161	260
174192	0.1817	69
174191	0.1798	67
174196	0.0185	8

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.00	gold quality
prefrontal cortex	UBERON:0000451	91.12	gold quality
amygdala	UBERON:0001876	90.99	gold quality
temporal lobe	UBERON:0001871	90.91	gold quality
anterior cingulate cortex	UBERON:0009835	90.60	gold quality
frontal cortex	UBERON:0001870	89.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.97	gold quality
primary visual cortex	UBERON:0002436	89.79	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.56	gold quality
cerebral cortex	UBERON:0000956	89.35	gold quality
right frontal lobe	UBERON:0002810	89.29	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.87	gold quality
Ammon’s horn	UBERON:0001954	88.41	gold quality
substantia nigra	UBERON:0002038	86.99	gold quality
hypothalamus	UBERON:0001898	86.91	gold quality
superior frontal gyrus	UBERON:0002661	86.08	gold quality
brain	UBERON:0000955	82.77	gold quality
cortical plate	UBERON:0005343	81.36	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.93	gold quality
cerebellum	UBERON:0002037	78.65	gold quality
cerebellar hemisphere	UBERON:0002245	78.60	gold quality
cerebellar cortex	UBERON:0002129	78.56	gold quality
putamen	UBERON:0001874	77.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.67	gold quality
ganglionic eminence	UBERON:0004023	76.51	gold quality
nucleus accumbens	UBERON:0001882	76.17	gold quality
apex of heart	UBERON:0002098	75.55	gold quality
caudate nucleus	UBERON:0001873	75.28	gold quality
testis	UBERON:0000473	73.10	gold quality
right testis	UBERON:0004534	72.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting NANOS3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-640	98.44	66.93	644
HSA-MIR-1226-5P	96.50	65.28	643
HSA-MIR-193A-5P	95.70	65.33	613
HSA-MIR-1915-5P	95.25	65.78	571

Literature-anchored findings (GeneRIF, showing 9)

• Mutations in NANOS3 exons are rare in both Chinese and Caucasian women with premature ovarian failure. (PMID:17418157)
• Report for the first time analysis of the NANOS3 gene in infertile males. (PMID:19565640)
• NANOS3 modulates essential aspects of human germ cell development perhaps during the cell cycle. (PMID:21421998)
• NANOS3 mutation is one possible cause of primary ovarian insufficiency. (PMID:24091668)
• an inactivating missense mutation in NANOS3 has a role in primary ovarian insufficiency that involves increased primordial germ cell apoptosis during embryonic cell migration (PMID:25054146)
• NANOS3 has role in the acquisition of invasiveness by human lung tumour cells and propose a new mechanism of post-transcriptional regulation of epithelial-mesenchymal transition. (PMID:25904364)
• data can be used to further elucidate the role of NANOS3 and DAZL in germ cell development both in vitro and in vivo (PMID:27768780)
• despite the prominent role of NANOS3 in ovarian development, our findings suggest that NANOS3 mutations were not associated with POF in the present cohort of Brazilian women. (PMID:28076512)
• Gene Alterations and Expression Spectrum of NANOS3 in Nonobstructive Azoospermia. (PMID:34417763)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nanos3	ENSDARG00000068255
mus_musculus	Nanos3	ENSMUSG00000056155
rattus_norvegicus	Nanos3	ENSRNOG00000031593
drosophila_melanogaster	nanos	FBGN0002962
caenorhabditis_elegans		WBGENE00003783
caenorhabditis_elegans		WBGENE00003784

Paralogs (2): NANOS2 (ENSG00000188425), NANOS1 (ENSG00000188613)

Protein

Protein identifiers

Nanos homolog 3 — P60323 (reviewed: P60323)

All UniProt accessions (1): P60323

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the maintenance of the undifferentiated state of germ cells regulating the spermatogonia cell cycle and inducing a prolonged transit in G1 phase. Affects cell proliferation probably by repressing translation of specific mRNAs. Maintains the germ cell lineage by suppressing both Bax-dependent and -independent apoptotic pathways. Essential in the early stage embryo to protect the migrating primordial germ cells (PGCs) from apoptosis.

Subunit / interactions. Binds mRNA from germ cells. Interacts with PUM2.

Subcellular location. Nucleus. Cytoplasm. Stress granule. P-body.

Tissue specificity. Ovary, testis and brain (at protein level). In the ovaries, expressed during multiple stages of oogenesis, including primordial, primary, secondary and antral follicles with the highest expression in the oocytes. In the testis, expressed in germ cells, type A spermatogonia (SA), primary spermatocytes (S1), round spermatids (S3) and elongated spermatids.

Domain organisation. The Nanos-type zinc finger is composed of two C2HC motifs, each motif binding one molecule of zinc. It is essential for the translation repression activity of the protein.

Similarity. Belongs to the nanos family.

Isoforms (2)

UniProt ID	Names	Canonical?
P60323-1	1	yes
P60323-2	2

RefSeq proteins (1): NP_001092092* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008705	Nanos/Xcar2	Family
IPR024161	Znf_nanos-typ	Domain
IPR038129	Nanos_sf	Homologous_superfamily

Pfam: PF05741

UniProt features (21 total): binding site 8, site 4, region of interest 2, short sequence motif 2, compositionally biased region 2, chain 1, zinc finger region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60323-F1	71.75	0.33

Functional residue map

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

Catalytic / active sites (4): 62 (involved in rna binding); 77 (involved in rna binding); 89 (involved in rna binding); 107 (involved in rna binding)

Ligand- & substrate-binding residues (8): 74; 85; 93; 96; 104; 109; 58; 61

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9827857	Specification of primordial germ cells
R-HSA-1474165	Reproduction

MSigDB gene sets: 505 (showing top): PID_SHP2_PATHWAY, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_POTASSIUM_ION_TRANSPORT, BIOCARTA_GCR_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT

GO Biological Process (10): regulation of translation (GO:0006417), germ cell development (GO:0007281), spermatogenesis (GO:0007283), negative regulation of translation (GO:0017148), oogenesis (GO:0048477), regulation of cell cycle (GO:0051726), mRNA destabilization (GO:0061157), apoptotic signaling pathway (GO:0097190), negative regulation of apoptotic signaling pathway (GO:2001234), cell differentiation (GO:0030154)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA binding (GO:0003729), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): P-body (GO:0000932), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Reproduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
translation	2
developmental process involved in reproduction	2
negative regulation of gene expression	2
cytoplasmic ribonucleoprotein granule	2
cytoplasm	2
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
male gamete generation	1
regulation of translation	1
negative regulation of protein metabolic process	1
germ cell development	1
female gamete generation	1
cell cycle	1
regulation of cellular process	1
regulation of mRNA stability	1
RNA destabilization	1
positive regulation of mRNA catabolic process	1
apoptotic process	1
signal transduction	1
negative regulation of signal transduction	1
negative regulation of apoptotic process	1
apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
cellular developmental process	1
nucleic acid binding	1
RNA binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

912 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NANOS3	DAZL	Q92904	853
NANOS3	DND1	Q8IYX4	807
NANOS3	PRDM14	Q9GZV8	794
NANOS3	STRA8	Q7Z7C7	685
NANOS3	DDX4	Q9NQI0	679
NANOS3	TFAP2C	Q92754	665
NANOS3	ZBTB16	Q05516	652
NANOS3	PRDM1	O75626	651
NANOS3	GFRA1	P56159	614
NANOS3	SYCP3	Q8IZU3	610
NANOS3	SOHLH1	Q5JUK2	603
NANOS3	DMRT1	Q9Y5R6	598
NANOS3	SOHLH2	Q9NX45	597
NANOS3	TDRD5	Q8NAT2	595
NANOS3	UTF1	Q5T230	593
NANOS3	NOBOX	O60393	593

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): NANOS3 (Affinity Capture-Western), CNOT1 (Affinity Capture-Western), CNOT3 (Affinity Capture-Western), CNOT1 (Reconstituted Complex), NANOS3 (Phenotypic Enhancement), NANOS3 (Protein-RNA), NANOS3 (Two-hybrid), NANOS3 (Two-hybrid), NANOS3 (Two-hybrid), NANOS3 (Two-hybrid), NANOS3 (Two-hybrid), NANOS3 (Affinity Capture-MS), NANOS3 (Affinity Capture-MS), NANOS3 (Affinity Capture-MS), NANOS3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HJK9, A9LMC0, B2RVL6, B5DEH0, C3VD30, G5E5X0, O43900, O54880, O95343, P0DH66, P46686, P56163, P58269, P60321, P60322, P60323, P60324, Q07937, Q29RJ0, Q2PFD7, Q38740, Q3UPF5, Q58D79, Q5TKR9, Q5XIX0, Q61103, Q62233, Q6Y2X3, Q705F3, Q768S4, Q7Z2W4, Q80U38, Q8BZ21, Q8CCG1, Q8HXK7, Q8K3Y6, Q8N2G6, Q90WW1, Q90ZZ5, Q90ZZ6

Diamond homologs: E7FDB3, P25724, P60321, P60322, P60323, P60324, Q07937, Q80WY3, Q8WY41, Q90WW1, Q90ZZ5, Q90ZZ6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
“CCR4-NOT complex”	“down-regulates quantity by repression”	NANOS3	“post transcriptional regulation”
SOX17/POU5F1	“up-regulates quantity by expression”	NANOS3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	131
Likely benign	29
Benign	36

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
4686577	NOS3, IVS12, G-C, +1	Pathogenic
4686578	C648R	Pathogenic
929757	NM_000603.5(NOS3):c.172C>T (p.Pro58Ser)	Likely pathogenic
929758	NM_000603.5(NOS3):c.505G>A (p.Glu169Lys)	Likely pathogenic

SpliceAI

4334 predictions. Top by Δscore:

Variant	Effect	Δscore
19:13877757:G:GT	donor_gain	1.0000
7:150996862:GGC:G	donor_gain	1.0000
7:150996970:G:T	donor_gain	1.0000
7:150998325:A:AG	acceptor_gain	1.0000
7:150998326:C:G	acceptor_gain	1.0000
7:150998337:C:CA	acceptor_gain	1.0000
7:150998340:T:TA	acceptor_gain	1.0000
7:150998345:C:CA	acceptor_gain	1.0000
7:150998349:T:A	acceptor_gain	1.0000
7:150998444:CTTCG:C	donor_gain	1.0000
7:150998445:TTCG:T	donor_gain	1.0000
7:150998446:TCG:T	donor_gain	1.0000
7:150998448:GGTG:G	donor_loss	1.0000
7:150998449:G:GG	donor_gain	1.0000
7:150998449:G:T	donor_loss	1.0000
7:150998450:T:A	donor_loss	1.0000
7:150998528:A:AG	acceptor_gain	1.0000
7:150998528:AT:A	acceptor_gain	1.0000
7:150998528:ATGC:A	acceptor_gain	1.0000
7:150998529:T:G	acceptor_gain	1.0000
7:150998529:T:TA	acceptor_gain	1.0000
7:150998531:C:CA	acceptor_gain	1.0000
7:150998533:T:TA	acceptor_gain	1.0000
7:150998537:A:AG	acceptor_gain	1.0000
7:150998537:AGCTC:A	acceptor_gain	1.0000
7:150998538:G:GA	acceptor_gain	1.0000
7:150998538:GCTC:G	acceptor_gain	1.0000
7:150998538:GCTCG:G	acceptor_gain	1.0000
7:150998636:G:GT	donor_gain	1.0000
7:150998679:AG:A	donor_loss	1.0000

AlphaMissense

1209 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:13877483:T:C	F60L	1.000
19:13877484:T:G	F60C	1.000
19:13877485:C:A	F60L	1.000
19:13877485:C:G	F60L	1.000
19:13877558:T:C	C85R	1.000
19:13877582:T:C	C93R	1.000
19:13877627:T:C	F108L	1.000
19:13877629:C:A	F108L	1.000
19:13877629:C:G	F108L	1.000
19:13877484:T:C	F60S	0.999
19:13877486:T:A	C61S	0.999
19:13877487:G:A	C61Y	0.999
19:13877487:G:C	C61S	0.999
19:13877527:C:A	H74Q	0.999
19:13877527:C:G	H74Q	0.999
19:13877536:G:C	K77N	0.999
19:13877536:G:T	K77N	0.999
19:13877558:T:A	C85S	0.999
19:13877559:G:C	C85S	0.999
19:13877568:T:A	L88Q	0.999
19:13877568:T:C	L88P	0.999
19:13877591:T:A	C96S	0.999
19:13877591:T:C	C96R	0.999
19:13877592:G:C	C96S	0.999
19:13877613:C:A	A103D	0.999
19:13877615:C:G	H104D	0.999
19:13877617:C:A	H104Q	0.999
19:13877617:C:G	H104Q	0.999
19:13877630:T:C	C109R	0.999
19:13877477:T:A	C58S	0.998

dbSNP variants (sampled 300 via entrez): RS1000108848 (19:13877147 G>A), RS1000294725 (19:13876323 T>C), RS1000388893 (19:13866873 CCACACACACACA>C,CCACACACA,CCACACACACA,CCACACACACACACA,CCACACACACACACACA), RS1000691105 (19:13863810 T>C), RS1000785257 (19:13863573 G>A), RS1000840493 (19:13861186 T>C,G), RS1000936245 (19:13867281 G>A), RS1000987125 (19:13867054 C>T), RS1000989621 (19:13868010 T>A), RS1001098416 (19:13872756 A>G), RS1001098640 (19:13872095 C>T), RS1001144293 (19:13862928 C>T), RS1001195584 (19:13864679 C>G,T), RS1001355704 (19:13870348 T>C), RS1001414808 (19:13872281 A>G)

Disease associations

OMIM: gene MIM:608229 | disease phenotypes: MIM:104300, MIM:145500, MIM:189800, MIM:621469

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ovarian failure	Moderate	Semidominant

Mondo (8): Alzheimer disease (MONDO:0004975), Alzheimer disease type 1 (MONDO:0007088), essential hypertension, genetic (MONDO:0007781), preeclampsia/eclampsia 1 (MONDO:0100467), ischemic stroke (MONDO:1060198), Moyamoya disease 8 (MONDO:0980949), primary ovarian failure (MONDO:0005387), essential hypertension (MONDO:0001134)

Orphanet (4): Early-onset autosomal dominant Alzheimer disease (Orphanet:1020), NON RARE IN EUROPE: Alzheimer disease (Orphanet:238616), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Essential hypertension (Orphanet:243761)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0002511	Alzheimer disease

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST003116_2	Coronary artery disease	2.000000e-09
GCST003476_9	Eyebrow thickness	7.000000e-06
GCST004777_16	Diastolic blood pressure	2.000000e-13
GCST004787_39	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	2.000000e-12
GCST005194_47	Coronary artery disease	3.000000e-21
GCST005195_8	Coronary artery disease	1.000000e-20
GCST005196_154	Coronary artery disease	3.000000e-21
GCST005830_50	Hand grip strength	5.000000e-08
GCST006166_62	Diastolic blood pressure x alcohol consumption interaction (2df test)	4.000000e-31
GCST006187_20	Diastolic blood pressure (cigarette smoking interaction)	4.000000e-33
GCST006188_36	Systolic blood pressure (cigarette smoking interaction)	2.000000e-12
GCST006227_7	Diastolic blood pressure	2.000000e-16
GCST006228_8	Systolic blood pressure	5.000000e-12
GCST006229_2	Hypertension	3.000000e-09
GCST006231_34	Mean arterial pressure	2.000000e-08
GCST006434_110	Systolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-14
GCST007094_17	Diastolic blood pressure	4.000000e-23
GCST007099_100	Systolic blood pressure	2.000000e-09
GCST007248_1	Stroke	2.000000e-08
GCST007267_328	Systolic blood pressure	2.000000e-13
GCST007927_41	Medication use (beta blocking agents)	8.000000e-21
GCST007928_86	Medication use (diuretics)	7.000000e-29
GCST007929_10	Medication use (calcium channel blockers)	4.000000e-26
GCST007930_83	Medication use (agents acting on the renin-angiotensin system)	2.000000e-37
GCST007931_39	Medication use (HMG CoA reductase inhibitors)	7.000000e-11
GCST008363_64	Offspring birth weight	9.000000e-12
GCST008747_125	Estimated glomerular filtration rate	4.000000e-07
GCST010726_33	Periventricular white matter hyperintensities	4.000000e-08
GCST011364_10	Myocardial infarction	4.000000e-09
GCST011365_52	Myocardial infarction	4.000000e-13

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006941	grip strength measurement
EFO:0004329	alcohol drinking
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0009929	Beta blocking agent use measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0004980	appendicular lean mass
EFO:0007984	platelet component distribution width

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D000544	Alzheimer Disease	C10.228.140.380.100; C10.574.945.249; F03.615.400.100
D000075222	Essential Hypertension	C14.907.489.165
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C536594	Alzheimer disease type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

14 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1799983	Efficacy	3	Ace Inhibitors;Plain;Angiotensin II Antagonists;Beta Blocking Agents;digoxin;diuretics;spironolactone	Heart Failure
rs1799983	Efficacy	3	daunorubicin	Leukemia;Myeloid;Acute
rs1799983	Efficacy	3	salvianolic acid b	Coronary Disease
rs1799983	Efficacy	3	anthracyclines and related substances;cyclophosphamide;doxorubicin;epirubicin;fluorouracil;methotrexate;oxaliplatin;Platinum compounds	Neoplasms;Ovarian Neoplasms;Stomach Neoplasms
rs1799983	Toxicity	3	aspirin;Beta Blocking Agents;clopidogrel;HMG-CoA reductase inhibitors	Coronary Artery Disease
rs1799983	Efficacy	3	sorafenib	Hepatocellular Carcinoma
rs1799983	Efficacy	3	cyclophosphamide;doxorubicin;fluorouracil;methotrexate	Breast Neoplasms
rs1799983	Efficacy	3	nortriptyline	Migraine with Aura;Migraine without Aura
rs2070744	Efficacy	3	Antihypertensives And Diuretics In Combination
rs2070744	Efficacy	3	cyclophosphamide;doxorubicin;fluorouracil;methotrexate	Breast Neoplasms
rs2070744	Efficacy	3	Antihypertensives;Antihypertensives And Diuretics In Combination;diuretics	Hypertension
rs2070744	Efficacy	3	sildenafil	Erectile Dysfunction
rs2070744	Efficacy	3	enalapril	Hypertension
rs2070744	Efficacy	3	sorafenib	Hepatocellular Carcinoma

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1799983	NOS3	3	5.50	8	Ace Inhibitors;Plain;Angiotensin II Antagonists;Beta Blocking Agents;digoxin;diuretics;spironolactone;aspirin;Beta Blocking Agents;clopidogrel;HMG-CoA reductase inhibitors;cyclophosphamide;doxorubicin;fluorouracil;methotrexate;anthracyclines and related substances;cyclophosphamide;doxorubicin;epirubicin;fluorouracil;methotrexate;oxaliplatin;Platinum compounds;salvianolic acid b;daunorubicin;sorafenib;nortriptyline
rs2070744	NOS3	3	5.75	6	Antihypertensives;Antihypertensives And Diuretics In Combination;diuretics;Antihypertensives And Diuretics In Combination;cyclophosphamide;doxorubicin;fluorouracil;methotrexate;sildenafil;sorafenib;enalapril
rs61722009	NOS3		0.00	0

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

375 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00009191	PHASE4	COMPLETED	The Depression in Alzheimer’s Disease Study (DIADS)
NCT00009217	PHASE4	COMPLETED	Treatment of Behavioral Symptoms in Alzheimer’s Disease
NCT00018278	PHASE4	COMPLETED	Electrophysiologic Measures of Treatment Response in Alzheimer Disease
NCT00035204	PHASE4	COMPLETED	A Study of the Effects on Sleep, Attention, and Gastrointestinal Tolerance of Galantamine and Donepezil in Patients With Alzheimer’s Disease
NCT00042172	PHASE4	COMPLETED	Treatment for Early Memory Loss
NCT00046358	PHASE4	COMPLETED	The Effect of Short-Term Statins and NSAIDs on Levels of Beta-Amyloid, a Protein Associated With Alzheimer’s Disease
NCT00104442	PHASE4	COMPLETED	Study of the Effects of Current Drug Treatments on Levels of Certain Brain Chemicals in Alzheimer’s Disease
NCT00120874	PHASE4	COMPLETED	Memantine and Comprehensive, Individualized Management of Alzheimer’s Disease and Caregiver Training
NCT00142324	PHASE4	UNKNOWN	CALM-AD
NCT00165724	PHASE4	COMPLETED	Alzheimer’s Disease Long-term Follow-up Study (ALF Study)
NCT00165750	PHASE4	TERMINATED	Correlation Between Regional Brain Volume and Response to Donepezil Treatment in AD Patients
NCT00202124	PHASE4	COMPLETED	Double Blind Study of Trp01 in Patients With Alzheimer’s Disease
NCT00208819	PHASE4	COMPLETED	A Comparison of Two Standard Therapies in the Management of Dementia With Agitation
NCT00216515	PHASE4	COMPLETED	The Efficacy of Galantamine on the Attention and the Frontal Function of the Patients With Dementia of Alzheimer Type
NCT00230568	PHASE4	COMPLETED	EARTH 413: A Study of Aricept in Hispanic Patients With Mild to Moderate Alzheimer’s Disease (AD)
NCT00234637	PHASE4	COMPLETED	Rivastigmine Monotherapy and Combination Therapy With Memantine in Patients With Moderately Severe Alzheimer’s Disease Who Failed to Benefit From Previous Cholinesterase Inhibitor Treatment
NCT00245206	PHASE4	COMPLETED	Side Effects of Newer Antipsychotics in Older Adults
NCT00254033	PHASE4	COMPLETED	Apathy Associated With Alzheimer’s Disease
NCT00260624	PHASE4	COMPLETED	Escitalopram Treatment of Patients With Agitated Dementia
NCT00303277	PHASE4	COMPLETED	Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
NCT00305903	PHASE4	COMPLETED	Safety and Tolerability of Rivastigmine With Add-on Memantine in Patients With Probable Alzheimer’s Disease
NCT00306124	PHASE4	UNKNOWN	Dopaminergic Enhancement of Learning and Memory in Healthy Adults and Patients With Dementia/Mild Cognitive Impairment
NCT00334906	PHASE4	COMPLETED	Study of Memantine in Assessment of Selected Measures of Volumetric Magnetic Resonance Imaging (MRI) and Cognition in Moderate AD (Alzheimer’s Disease)
NCT00369603	PHASE4	TERMINATED	Functional Brain Imaging of Medication Treatment Response in Mild Alzheimer’s Disease Patients
NCT00375557	PHASE4	WITHDRAWN	Safety and Efficacy of Divalproex and Quetiapine in Elderly Alzheimer’s Dementia Patients
NCT00381381	PHASE4	COMPLETED	The Clinical Response of Choline Acetyltransferase and Apolipoprotein Epsilon Gene Polymorphisms to Donepezil in Alzheimer’s Disease
NCT00385684	PHASE4	COMPLETED	Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
NCT00401167	PHASE4	COMPLETED	Memantine for Agitation and Aggression in Severe Alzheimer’s Disease
NCT00403520	PHASE4	COMPLETED	Hippocampus Study: Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers
NCT00417482	PHASE4	COMPLETED	Antipsychotic Discontinuation in Alzheimer’s Disease
NCT00443014	PHASE4	COMPLETED	The Dementia Study in Northern Norway
NCT00469456	PHASE4	COMPLETED	Effect of Memantine on Functional Communication in Patients With Alzheimer’s Disease
NCT00476008	PHASE4	COMPLETED	Delaying the Progression of Driving Impairment in Individuals With Mild Alzheimer’s Disease
NCT00477659	PHASE4	COMPLETED	Neural Correlates In Mild Alzheimer’s Disease