GINS3

Chr 16

GINS complex subunit 3

Also known as: MGORS9, PSF3

NCBI Gene: 64785ENSG00000181938UniProt: Q9BRX5

The protein is a subunit of the GINS heterotetrameric complex, which is essential for DNA replication initiation and replisome progression by functioning as a core component of the CDC45-MCM-GINS helicase that unwinds template DNA during replication. Mutations cause Meier-Gorlin syndrome 9, inherited in an autosomal recessive pattern. The pathogenic mechanism involves disruption of DNA replication machinery, leading to the characteristic growth retardation and developmental abnormalities seen in Meier-Gorlin syndrome.

Summary from RefSeq, OMIM, UniProt

Primary Disease Associations & Inheritance

Meier-Gorlin syndrome 9MIM #621512
0
Active trials
0
Pubs (1 yr)
26
P/LP submissions
8%
P/LP missense
1.52
LOEUF
DN
Mechanism· predicted
Clinical Summary— GINS3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 49 VUS of 79 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.52LOEUF
pLI 0.000
Z-score 0.42
OE 0.85 (0.50–1.52)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.46Z-score
OE missense 0.89 (0.76–1.03)
118 obs / 132.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.85 (0.50–1.52)
0≤0.351.4
Missense OE0.89 (0.76–1.03)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 8 / 9.4Missense obs/exp: 118 / 132.9Syn Z: -0.43
DN
0.6552th %ile
GOF
0.3788th %ile
LOF
0.3649th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

79 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic3
VUS49
Likely Benign1
22
Pathogenic
3
Likely Pathogenic
49
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
20
0
22
Likely Pathogenic
0
0
3
0
3
VUS
0
41
8
0
49
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total04431075

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

View in ClinVar →

Protein Context — Lollipop Plot

GINS3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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