PSMC3IP

Chr 17AR

PSMC3 interacting protein

Also known as: GT198, HOP2, HUMGT198A, ODG3, TBPIP

NCBI Gene: 29893ENSG00000131470UniProt: Q9P2W1

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. [provided by RefSeq, Dec 2011]

Primary Disease Associations & Inheritance

Ovarian dysgenesis 3MIM #614324
AR
0
Active trials
16
Pathogenic / LP
82
ClinVar variants
3
Pubs (1 yr)
-0.4
Missense Z
1.08
LOEUF
Clinical Summary— PSMC3IP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 42 VUS of 82 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.08LOEUF
pLI 0.000
Z-score 1.33
OE 0.62 (0.37–1.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.43Z-score
OE missense 1.11 (0.96–1.29)
126 obs / 113.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.62 (0.37–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (0.96–1.29)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 9 / 14.5Missense obs/exp: 126 / 113.1Syn Z: 0.00

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS42
Likely Benign12
Benign12
14
Pathogenic
2
Likely Pathogenic
42
VUS
12
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
11
0
14
Likely Pathogenic
0
0
2
0
2
VUS
0
37
5
0
42
Likely Benign
0
2
6
4
12
Benign
0
1
8
3
12
Total24132782

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PSMC3IP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ovarian dysgenesis 3

MIM #614324

Molecular basis of disorder known

Autosomal recessive

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Whole-exome sequencing in patients with maturation arrest: a potential additional diagnostic tool for prevention of recurrent negative testicular sperm extraction outcomes.
Ghieh F et al.·Hum Reprod
2022Cohort
Meiosis interrupted: the genetics of female infertility via meiotic failure.
Biswas L et al.·Reproduction
2021Review
Oct4 confers stemness and radioresistance to head and neck squamous cell carcinoma by regulating the homologous recombination factors PSMC3IP and RAD54L.
Nathansen J et al.·Oncogene
2021
Primary Ovarian Insufficiency and Azoospermia in Carriers of a Homozygous PSMC3IP Stop Gain Mutation.
Al-Agha AE et al.·J Clin Endocrinol Metab
2018Case report
PSMC3IP as a prognostic biomarker and immunomodulatory regulator in low-grade glioma: insights from multi-omics and methylation analysis.
Zhang Z et al.·Neurol Res
2026
Two novel biallelic mutations in PSMC3IP in a patient affected by premature ovarian insufficiency.
Mei L et al.·Mol Med Rep
2022
A Tiered Approach to Exome Sequencing Analysis in Early-Onset Primary Ovarian Insufficiency.
McGlacken-Byrne SM et al.·J Clin Endocrinol Metab
2025
No mutations in the PSMC3IP gene identified in a Swedish cohort of women with primary ovarian insufficiency.
Norling A et al.·Sex Dev
2014Cohort
Investigation of the molecular genetic causes of non-syndromic primary ovarian ınsufficiency by next generation sequencing analysis.
Er E et al.·Arch Endocrinol Metab
2023
Gene variants identified by whole-exome sequencing in 33 French women with premature ovarian insufficiency.
Yang X et al.·J Assist Reprod Genet
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients