PSMC3IP

Summary

PSMC3IP (PSMC3 interacting protein, HGNC:17928) is a protein-coding gene on chromosome 17q21.2, encoding Homologous-pairing protein 2 homolog (Q9P2W1). Plays an important role in meiotic recombination.

This gene encodes a protein that functions in meiotic recombination. It is a subunit of the PSMC3IP/MND1 complex, which interacts with PSMC3/TBP1 to stimulate DMC1- and RAD51-mediated strand exchange during meiosis. The protein encoded by this gene can also co-activate ligand-driven transcription mediated by estrogen, androgen, glucocorticoid, progesterone, and thyroid nuclear receptors. Mutations in this gene cause XX female gonadal dysgenesis. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 29893 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ovarian dysgenesis 3 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 61 total — 6 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 31
• MANE Select transcript: NM_016556

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17928
Approved symbol	PSMC3IP
Name	PSMC3 interacting protein
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	TBPIP, GT198, HUMGT198A, Hop2
Ensembl gene	ENSG00000131470
Ensembl biotype	protein_coding
OMIM	608665
Entrez	29893

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000253789, ENST00000393795, ENST00000586337, ENST00000587209, ENST00000587268, ENST00000588544, ENST00000589505, ENST00000590760, ENST00000590931

RefSeq mRNA: 5 — MANE Select: NM_016556 NM_001256014, NM_001256015, NM_001256016, NM_013290, NM_016556

CCDS: CCDS11431, CCDS45688, CCDS59289

Canonical transcript exons

ENST00000393795 — 8 exons

Exon	Start	End
ENSE00002846032	42572310	42573024
ENSE00003495520	42577461	42577561
ENSE00003626596	42573311	42573364
ENSE00003627421	42573107	42573166
ENSE00003633461	42574099	42574210
ENSE00003651599	42577213	42577302
ENSE00003683489	42573478	42573623
ENSE00003903566	42577653	42577729

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 95.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.9388 / max 271.3708, expressed in 1532 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166169	7.9388	1532

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	95.89	gold quality
left testis	UBERON:0004533	90.47	gold quality
right testis	UBERON:0004534	90.40	gold quality
testis	UBERON:0000473	89.75	gold quality
medial globus pallidus	UBERON:0002477	89.64	gold quality
sperm	CL:0000019	89.22	gold quality
ventricular zone	UBERON:0003053	89.17	gold quality
ganglionic eminence	UBERON:0004023	87.92	gold quality
male germ cell	CL:0000015	87.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.55	gold quality
buccal mucosa cell	CL:0002336	87.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.21	gold quality
globus pallidus	UBERON:0001875	85.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.28	gold quality
tendon	UBERON:0000043	84.47	gold quality
sural nerve	UBERON:0015488	84.47	gold quality
cortical plate	UBERON:0005343	84.04	gold quality
spinal cord	UBERON:0002240	83.79	gold quality
embryo	UBERON:0000922	83.53	gold quality
oviduct epithelium	UBERON:0004804	83.10	gold quality
gingival epithelium	UBERON:0001949	82.19	gold quality
secondary oocyte	CL:0000655	81.99	gold quality
lower esophagus mucosa	UBERON:0035834	80.78	gold quality
bronchial epithelial cell	CL:0002328	80.13	gold quality
gingiva	UBERON:0001828	80.07	gold quality
putamen	UBERON:0001874	80.07	gold quality
tibial nerve	UBERON:0001323	80.06	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	79.87	gold quality
fallopian tube	UBERON:0003889	79.53	gold quality
amniotic fluid	UBERON:0000173	79.36	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	170.51
E-GEOD-99795	yes	86.77
E-ANND-3	no	1.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

30 targeting PSMC3IP, 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-3163	100.00	77.23	8605
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-5189-3P	97.52	66.33	487
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-3126-3P	97.17	66.51	468
HSA-MIR-6894-3P	96.73	65.64	798
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-2114-3P	95.45	66.11	579

Literature-anchored findings (GeneRIF, showing 11)

• Identification of GT198 (TBPIP/Hop2) as a nuclear receptor coactivator. GT198 is phosphorylation regulated. GT198 interacts with nuclear receptors. (PMID:11739747)
• Data suggest that the human TBPIP/Hop2-Mnd1 complex may ensure proper pairing between homologous chromosomes through its stimulation of strand exchange during meiosis. (PMID:16407260)
• findings suggest that a component of 19S regulatory particles directly binds AR and might participate in AR-mediated transcriptional activation in cooperation with TBPIP. (PMID:19325002)
• a PSMC3IP/HOP2 mutation may cause XX ovarian dysgenesis through abolishing coactivation of estrogen-driven transcription (PMID:21963259)
• GT198 mutant luteinized theca cells overexpressing CYP17 are common in ovarian cancer stroma. (PMID:24097974)
• PSMC3IP gene mutations are not common causes of primary ovarian insufficiency in this Swedish cohort. (PMID:24481226)
• The PSMC3IP mutation provides additional evidence that mutations in meiotic homologous recombination and DNA repair genes result in distinct female and male reproductive phenotypes, including delayed puberty and primary amenorrhea caused by Primary ovarian insufficiency (XX gonadal dysgenesis) in females but isolated azoospermia with normal pubertal development in males. (PMID:29240891)
• targeting PSMC3IP maybe a promising strategy for Hepatocellular carcinoma. (PMID:30362169)
• Pathogenic variant in PSMC3IP gene is associated with premature ovarian insufficiency. (PMID:30406445)
• Oct4 confers stemness and radioresistance to head and neck squamous cell carcinoma by regulating the homologous recombination factors PSMC3IP and RAD54L. (PMID:34079088)
• Two novel biallelic mutations in PSMC3IP in a patient affected by premature ovarian insufficiency. (PMID:34878148)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmc3ip	ENSDARG00000037892
mus_musculus	Psmc3ip	ENSMUSG00000019303
rattus_norvegicus	Psmc3ip	ENSRNOG00000020022

Protein

Protein identifiers

Homologous-pairing protein 2 homolog — Q9P2W1 (reviewed: Q9P2W1)

Alternative names: Nuclear receptor coactivator GT198, PSMC3-interacting protein, Proteasome 26S ATPase subunit 3-interacting protein, Tat-binding protein 1-interacting protein

All UniProt accessions (6): A0A158RUX1, Q9P2W1, K7EK12, K7ELD8, K7EQS1, K7ERB6

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in meiotic recombination. Stimulates DMC1-mediated strand exchange required for pairing homologous chromosomes during meiosis. The complex PSMC3IP/MND1 binds DNA, stimulates the recombinase activity of DMC1 as well as DMC1 D-loop formation from double-strand DNA. This complex stabilizes presynaptic RAD51 and DMC1 filaments formed on single strand DNA to capture double-strand DNA. This complex stimulates both synaptic and presynaptic critical steps in RAD51 and DMC1-promoted homologous pairing. May inhibit HIV-1 viral protein TAT activity and modulate the activity of proteasomes through association with PSMC3. Acts as a tissue specific coactivator of hormone-dependent transcription mediated by nuclear receptors.

Subunit / interactions. Interacts with the DNA-binding domain of the nuclear receptors NR3C1/GR, ESR2/ER-beta, THRB and RXRA. Forms a stable heterodimer with MND1. Interacts with PSMC3/TBP1.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in testis and colon.

Post-translational modifications. PTM: Phosphorylated by PKA, PKC and MAPK.

Disease relevance. Ovarian dysgenesis 3 (ODG3) [MIM:614324] A disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. The disease is caused by variants affecting the gene represented in this entry.

Induction. Overexpressed in leiomyomas compared to myometrium.

Similarity. Belongs to the HOP2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9P2W1-1	1	yes
Q9P2W1-2	2
Q9P2W1-3	3

RefSeq proteins (5): NP_001242943, NP_001242944, NP_001242945, NP_037422, NP_057640* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010776	Hop2_WH_dom	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR040661	LZ3wCH	Domain

Pfam: PF07106, PF18517

UniProt features (10 total): sequence conflict 3, splice variant 2, sequence variant 2, chain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2W1-F1	92.45	0.85

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-912446	Meiotic recombination

MSigDB gene sets: 247 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, REACTOME_MEIOTIC_RECOMBINATION, GOBP_CHROMOSOME_ORGANIZATION, WANG_CLIM2_TARGETS_UP, MYOGENIN_Q6, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOLDRATH_ANTIGEN_RESPONSE, PUJANA_CHEK2_PCC_NETWORK, GOBP_ORGANELLE_FISSION, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, LIAO_METASTASIS

GO Biological Process (7): meiotic joint molecule formation (GO:0000709), homologous chromosome pairing at meiosis (GO:0007129), reciprocal meiotic recombination (GO:0007131), meiotic strand invasion involved in reciprocal meiotic recombination (GO:0010774), DNA recombination (GO:0006310), positive regulation of DNA-templated transcription (GO:0045893), meiotic cell cycle (GO:0051321)

GO Molecular Function (5): double-stranded DNA binding (GO:0003690), transcription coactivator activity (GO:0003713), recombinase activator activity (GO:0120230), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): condensed nuclear chromosome (GO:0000794), nucleoplasm (GO:0005654), DNA recombinase auxiliary factor complex (GO:0120231), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Meiosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
reciprocal meiotic recombination	2
meiotic cell cycle process	2
homologous chromosome segregation	1
chromosome organization involved in meiotic cell cycle	1
meiosis I	1
reciprocal homologous recombination	1
meiotic strand invasion	1
DNA metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
DNA binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
enzyme activator activity	1
nucleic acid binding	1
binding	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
nuclear lumen	1
cellular anatomical structure	1
enzyme activator complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMC3IP	MND1	Q9BWT6	962
PSMC3IP	RAD51	Q06609	689
PSMC3IP	PSMC3	P17980	687
PSMC3IP	MCM9	Q9NXL9	633
PSMC3IP	MSH4	O15457	625
PSMC3IP	SYCE1	Q8N0S2	600
PSMC3IP	DMC1	Q14565	593
PSMC3IP	HFM1	A2PYH4	565
PSMC3IP	SPO11	Q9Y5K1	560
PSMC3IP	MCM8	Q9UJA3	553
PSMC3IP	STAG3	Q9UJ98	533
PSMC3IP	A0A494C100	A0A494C100	525
PSMC3IP	BRCA1	P38398	509
PSMC3IP	HORMAD1	Q86X24	474
PSMC3IP	HSF2BP	O75031	462

IntAct

30 interactions, top by confidence:

A	B	Type	Score
PSMC3IP	MND1	psi-mi:“MI:0407”(direct interaction)	0.900
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
KXD1	TRAK2	psi-mi:“MI:0914”(association)	0.530
PSMC3IP	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
AURKA	PSMC3IP	psi-mi:“MI:0915”(physical association)	0.370
BCAR3	PSMC3IP	psi-mi:“MI:0915”(physical association)	0.370
PSMC3IP	BRMS1	psi-mi:“MI:0915”(physical association)	0.370
CASP8	PSMC3IP	psi-mi:“MI:0915”(physical association)	0.370
CDH1	PSMC3IP	psi-mi:“MI:0915”(physical association)	0.370
PSMC3IP	CHEK2	psi-mi:“MI:0915”(physical association)	0.370
PSMC3IP	ERBB2	psi-mi:“MI:0915”(physical association)	0.370
ESR1	PSMC3IP	psi-mi:“MI:0915”(physical association)	0.370
PSMC3IP	FGFR4	psi-mi:“MI:0915”(physical association)	0.370
PSMC3IP	NOTCH2	psi-mi:“MI:0915”(physical association)	0.370
PIK3CA	PSMC3IP	psi-mi:“MI:0915”(physical association)	0.370
RB1CC1	PSMC3IP	psi-mi:“MI:0915”(physical association)	0.370
TGFB1	PSMC3IP	psi-mi:“MI:0915”(physical association)	0.370
XRCC3	PSMC3IP	psi-mi:“MI:0915”(physical association)	0.370
MND1	IK	psi-mi:“MI:0914”(association)	0.350
MND1	SPAG9	psi-mi:“MI:0914”(association)	0.350
PSMC3IP	CCNB1	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
KRT37	ANKRD36	psi-mi:“MI:0914”(association)	0.350
EIF1AD	CHEK1	psi-mi:“MI:0914”(association)	0.350
MND1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
MND1		psi-mi:“MI:0914”(association)	0.350

BioGRID (48): PSMC3IP (Co-fractionation), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid), PSMC3IP (Two-hybrid)

ESM2 similar proteins: A7S2N8, B0DOB5, O35047, O35594, O65902, P09874, P11103, P18493, P26446, P27008, P31669, P50533, P53102, P53187, P53620, P55010, P59325, P81127, P83829, Q07205, Q09739, Q148K0, Q15560, Q29M42, Q2TBL4, Q4AEF8, Q5R4L0, Q5RHR0, Q5XIL3, Q63ZL2, Q6DKD7, Q8BPM0, Q8GYD2, Q8WYA0, Q91ZY6, Q99747, Q9BUI4, Q9C8F1, Q9CR26, Q9CWZ7

Diamond homologs: O35047, Q63ZL2, Q91ZY6, Q9FX64, Q9P2W1, Q54UM1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of gene expression	6	15.3×	6e-04
heart development	5	14.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	2
Uncertain significance	29
Likely benign	10
Benign	10

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
3901233	PSMC3IP, TYR163TER	Pathogenic
3901234	PSMC3IP, 2-BP INS, 430GA	Pathogenic
3901235	PSMC3IP, 2-BP DEL, 496CT	Pathogenic
3901236	D90H	Pathogenic
3901237	c.597+1G-T	Pathogenic
3901240	NM_016556.4(PSMC3IP):c.215T>C (p.Phe72Ser)	Pathogenic
3342726	NM_016556.4(PSMC3IP):c.203AGA[1] (p.Lys69del)	Likely pathogenic
3780497	NM_016556.4(PSMC3IP):c.310C>T (p.Gln104Ter)	Likely pathogenic

SpliceAI

1043 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42573102:CTTA:C	donor_loss	1.0000
17:42573103:TTAC:T	donor_loss	1.0000
17:42573104:TAC:T	donor_loss	1.0000
17:42573105:A:AC	donor_gain	1.0000
17:42573105:AC:A	donor_loss	1.0000
17:42573106:C:CA	donor_loss	1.0000
17:42573106:C:CC	donor_gain	1.0000
17:42577208:CTCA:C	donor_loss	1.0000
17:42577210:CA:C	donor_loss	1.0000
17:42577212:C:CG	donor_loss	1.0000
17:42577299:CCAC:C	acceptor_gain	1.0000
17:42577300:CAC:C	acceptor_gain	1.0000
17:42577300:CACC:C	acceptor_gain	1.0000
17:42577303:C:CA	acceptor_loss	1.0000
17:42577303:C:CC	acceptor_gain	1.0000
17:42577304:T:A	acceptor_loss	1.0000
17:42577307:C:CT	acceptor_gain	1.0000
17:42577308:A:T	acceptor_gain	1.0000
17:42577504:T:TA	donor_gain	1.0000
17:42577648:GTTA:G	donor_loss	1.0000
17:42577649:TTACC:T	donor_loss	1.0000
17:42577652:CC:C	donor_loss	1.0000
17:42577654:T:TA	donor_gain	1.0000
17:42577655:C:A	donor_gain	1.0000
17:42577685:ATCG:A	donor_gain	1.0000
17:42577686:T:C	donor_gain	1.0000
17:42577705:A:C	donor_gain	1.0000
17:42573024:CCTGT:C	acceptor_loss	0.9900
17:42573025:CTGT:C	acceptor_loss	0.9900
17:42573026:T:C	acceptor_loss	0.9900

AlphaMissense

1438 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42573144:A:T	I187K	0.987
17:42577227:A:C	Y71D	0.985
17:42577464:C:A	K44N	0.983
17:42577464:C:G	K44N	0.983
17:42577512:G:C	S28R	0.982
17:42577512:G:T	S28R	0.982
17:42577514:T:G	S28R	0.982
17:42573320:C:A	R176S	0.980
17:42573320:C:G	R176S	0.980
17:42577522:C:G	R25P	0.980
17:42577519:G:T	P26H	0.977
17:42573144:A:C	I187R	0.975
17:42573331:A:G	W173R	0.975
17:42573331:A:T	W173R	0.975
17:42577241:C:T	G66D	0.975
17:42573317:C:A	K177N	0.974
17:42573317:C:G	K177N	0.974
17:42577286:A:G	L51P	0.974
17:42577298:A:T	V47E	0.974
17:42577239:T:C	K67E	0.973
17:42577237:C:A	K67N	0.970
17:42577237:C:G	K67N	0.970
17:42577466:T:C	K44E	0.969
17:42577520:G:A	P26S	0.967
17:42573156:A:G	L183P	0.966
17:42577277:A:G	L54P	0.966
17:42577505:C:G	D31H	0.966
17:42577537:A:G	L20P	0.965
17:42577465:T:G	K44T	0.963
17:42577213:C:A	Q75H	0.962

dbSNP variants (sampled 300 via entrez): RS1000122210 (17:42578818 G>C), RS1000627953 (17:42579617 C>A), RS1000841194 (17:42573037 G>A), RS1000890947 (17:42573578 T>C,G), RS1001246946 (17:42579036 G>A), RS1001266851 (17:42579612 A>G), RS1001614905 (17:42576044 C>A,T), RS1001896070 (17:42574765 C>T), RS1002453540 (17:42579649 C>CG), RS1002813873 (17:42572217 T>C), RS1003817408 (17:42575411 A>G), RS1004192788 (17:42575774 C>T), RS1004295 (17:42575409 C>G,T), RS1004419169 (17:42575400 G>T), RS1004635406 (17:42579318 G>A,C)

Disease associations

OMIM: gene MIM:608665 | disease phenotypes: MIM:614324, MIM:233300

GenCC curated gene-disease

Disease	Classification	Inheritance
ovarian dysgenesis 3	Strong	Autosomal recessive
46 XX gonadal dysgenesis	Supportive	Autosomal dominant

Mondo (2): ovarian dysgenesis 3 (MONDO:0013689), 46 XX gonadal dysgenesis (MONDO:0009299)

Orphanet (1): 46,XX gonadal dysgenesis (Orphanet:243)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000062	Ambiguous genitalia
HP:0000133	Gonadal dysgenesis
HP:0000144	Decreased fertility
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000786	Primary amenorrhea
HP:0000823	Delayed puberty
HP:0000837	Increased circulating gonadotropin level
HP:0000869	Secondary amenorrhea
HP:0000938	Osteopenia
HP:0001166	Arachnodactyly
HP:0001251	Ataxia
HP:0001939	Abnormality of metabolism/homeostasis
HP:0002206	Pulmonary fibrosis
HP:0002225	Sparse pubic hair
HP:0002750	Delayed skeletal maturation
HP:0003621	Juvenile onset
HP:0004322	Short stature
HP:0004349	Reduced bone mineral density
HP:0005625	Osteoporosis of vertebrae
HP:0008209	Premature ovarian insufficiency
HP:0008214	Decreased serum estradiol
HP:0008222	Female infertility
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0008684	Aplasia/hypoplasia of the uterus
HP:0009888	Abnormality of secondary sexual hair
HP:0010311	Aplasia/Hypoplasia of the breasts
HP:0010463	Aplasia of the ovary
HP:0010464	Streak ovary

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003209_7	Colorectal or endometrial cancer	1.000000e-06
GCST90002407_137	White blood cell count	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004230	endometrial neoplasm

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D023961	Gonadal Dysgenesis, 46,XX	C12.050.351.875.253.064.249; C12.050.351.875.253.309.193; C12.200.706.316.064.249; C12.200.706.316.309.193; C12.800.316.064.249; C12.800.316.309.193; C16.131.939.316.064.249; C16.131.939.316.309.193; C19.391.119.064.249; C19.391.119.309.193

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	2
sodium arsenite	increases expression	2
Benzo(a)pyrene	increases expression	2
Cisplatin	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
afuresertib	decreases expression	1
lasiocarpine	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
2-palmitoylglycerol	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Adenine	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Colchicine	decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Lucanthone	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Niclosamide	decreases expression	1
Oxygen	decreases expression	1
Phenobarbital	affects expression	1

Clinical trials (associated diseases)

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