PSMC3IP

PSMC3 interacting protein

Basic information

Region (hg38): 17:42572309-42577831

Links

ENSG00000131470 ∙ NCBI:29893 ∙ OMIM:608665 ∙ HGNC:17928 ∙ Uniprot:Q9P2W1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 46 XX gonadal dysgenesis (Supportive), mode of inheritance: AD
• ovarian dysgenesis 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ovarian dysgenesis 3	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine; Genitourinary	21963259
To induce/maintain secondary sex characteristics, and to allow reproduction, specific interventions (eg, medical hormonal treatment) may be necessary

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSMC3IP gene.

• Ovarian dysgenesis 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMC3IP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	3	5
missense			15	1	1	17
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2	2	8	12
Total	1	0	17	5	12

Variants in PSMC3IP

This is a list of pathogenic ClinVar variants found in the PSMC3IP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-42572959-G-A			Benign (May 30, 2020)
17-42572988-C-A		not specified	Uncertain significance (Jun 27, 2023)
17-42573005-G-A		not specified	Uncertain significance (Apr 07, 2022)
17-42573007-CT-C		Ovarian dysgenesis 3	Pathogenic (Apr 22, 2019)
17-42573019-TTCC-T		Ovarian dysgenesis 3	Pathogenic (Oct 07, 2011)
17-42573084-AGAAG-A			Likely benign (Jun 13, 2023)
17-42573339-C-T		not specified	Uncertain significance (Jun 27, 2023)
17-42573361-A-T		not specified	Benign (Jan 26, 2024)
17-42573480-G-C			Uncertain significance (Aug 17, 2023)
17-42573487-C-G		not specified	Uncertain significance (Mar 04, 2024)
17-42573550-G-A		PSMC3IP-related disorder	Likely benign (Jun 18, 2019)
17-42573578-T-C		not specified	Uncertain significance (Dec 13, 2023)
17-42573582-G-C		not specified	Uncertain significance (Jan 17, 2023)
17-42573598-C-T			Benign (Jan 18, 2024)
17-42573621-G-C		not specified	Uncertain significance (Dec 26, 2023)
17-42573638-G-C		Ovarian dysgenesis 3	Benign (Jan 31, 2024)
17-42573770-A-G			Benign (Jun 05, 2020)
17-42573781-C-T			Benign (Jul 17, 2018)
17-42574011-G-A			Benign (Jun 05, 2020)
17-42574113-C-T		PSMC3IP-related disorder	Likely benign (Oct 11, 2023)
17-42574143-G-A		not specified	Uncertain significance (Jun 07, 2024)
17-42574156-C-T			Uncertain significance (Jan 12, 2017)
17-42574157-G-C		not specified	Uncertain significance (Mar 19, 2024)
17-42574174-C-G		not specified	Uncertain significance (Jan 08, 2024)
17-42574190-A-G			Benign (Dec 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMC3IP	protein_coding	protein_coding	ENST00000393795	8	5517

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000378	0.841	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.433	126	113	1.11	0.00000566	1436
Missense in Polyphen		40	36.118	1.1075		469
Synonymous	0.00191	44	44.0	1.00	0.00000238	373
Loss of Function	1.33	9	14.5	0.622	6.39e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000380	0.000380
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:10806355, ECO:0000269|PubMed:16407260, ECO:0000269|PubMed:21963259}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:21963259}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Androgen receptor signaling pathway;AndrogenReceptor (Consensus)

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.908
• rvis_EVS: -0.29
• rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

• pHI: 0.0699
• hipred: Y
• hipred_score: 0.637
• ghis: 0.550

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.595

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Psmc3ip
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; reproductive system phenotype

Gene ontology

• Biological process: DNA recombination;meiotic cell cycle;positive regulation of nucleic acid-templated transcription
• Cellular component: cellular_component;nucleoplasm
• Molecular function: DNA binding;nuclear receptor transcription coactivator activity