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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
GINS3
GINS complex subunit 3
Chromosome 16 Β· 16q21
NCBI Gene: 64785Ensembl: ENSG00000181938.15HGNC: HGNC:25851UniProt: A0A0S2Z5L0
64PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingDNA replicationnucleusnucleoplasmMeier-Gorlin syndrometrauma complicationcancercolorectal cancer
✦AI Summary

GINS3 (GINS complex subunit 3) is a core component of the GINS tetrameric complex, which functions as an essential scaffold within the CDC45-MCM-GINS (CMG) helicase 12. The CMG helicase unwinds template DNA during replication initiation and fork progression, with GINS3 required for proper helicase activity and CMG complex assembly 34. Mechanistically, GINS3 mediates critical protein-protein interactions at the replisome and facilitates DNA replication fork progression 5. Hypomorphic GINS3 variants cause Meier-Gorlin syndrome through compromised protein stability, impaired S-phase progression, and defective fork progression, demonstrating GINS3's essential role in normal cell proliferation 5. In model organisms, GINS3 variants result in intrauterine growth retardation and cellular senescence 5. Clinically, GINS3 is significantly upregulated across multiple malignancies. In hepatocellular carcinoma, elevated GINS3 correlates with poor prognosis, higher tumor stage, and immune checkpoint dysregulation 6. Similarly, high GINS3 expression associates with worse clinicopathological features in endometrial cancer 7. GINS3 upregulation represents a potential biomarker for cancer diagnosis and progression, though inhibiting GINS3-associated DNA replication signatures may improve therapeutic outcomes in platinum-resistant ovarian cancer 8.

Sources cited
1
GINS complex plays essential role in DNA replication initiation
PMID: 17417653
2
GINS complex required for DNA replication fork progression
PMID: 28414293
3
GINS complex is core component of CMG helicase that unwinds DNA
PMID: 32453425
4
GINS complex functions in CMG helicase and replisome assembly
PMID: 34694004
5
Hypomorphic GINS3 variants cause Meier-Gorlin syndrome through reduced protein stability and impaired DNA replication fork progression
PMID: 35603789
6
GINS3 upregulated in hepatocellular carcinoma and correlates with poor prognosis and immune dysregulation
PMID: 37304536
7
GINS3 associated with worse clinicopathological features in endometrial cancer
PMID: 35792121
8
High GINS3 expression associated with CHK1 inhibitor resistance in ovarian cancer
PMID: 38555285
Disease Associationsβ“˜20
Meier-Gorlin syndromeOpen Targets
0.37Weak
trauma complicationOpen Targets
0.10Suggestive
cancerOpen Targets
0.06Suggestive
colorectal cancerOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.04Suggestive
squamous cell carcinomaOpen Targets
0.04Suggestive
skull disorderOpen Targets
0.04Suggestive
non-small cell lung carcinomaOpen Targets
0.04Suggestive
adenocarcinomaOpen Targets
0.04Suggestive
Seckel syndromeOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.03Suggestive
lung adenocarcinomaOpen Targets
0.03Suggestive
colon carcinomaOpen Targets
0.03Suggestive
lung cancerOpen Targets
0.02Suggestive
nasopharyngeal carcinomaOpen Targets
0.02Suggestive
Mungan syndromeOpen Targets
0.02Suggestive
sarcomaOpen Targets
0.02Suggestive
osteosarcomaOpen Targets
0.02Suggestive
psoriasisOpen Targets
0.01Suggestive
endometrial carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants2
NM_022770.4(GINS3):c.70G>A (p.Asp24Asn)Pathogenic
Meier-Gorlin syndrome 9
β˜†β˜†β˜†β˜†2026β†’ Residue 24
NM_022770.4(GINS3):c.71A>G (p.Asp24Gly)Pathogenic
Meier-Gorlin syndrome 9
β˜†β˜†β˜†β˜†2026β†’ Residue 24
View on ClinVar β†—
Related Genes
ORC2Shared pathway100%POLEProtein interaction100%TIMELESSProtein interaction100%TOPBP1Protein interaction100%TIPINProtein interaction100%CDT1Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
60%
Brain
36%
Lung
14%
Liver
12%
Ovary
10%
Gene Interaction Network
Click a node to explore
GINS3ORC2POLETIMELESSTOPBP1TIPINCDT1
PROTEIN STRUCTURE
Preparing viewer…
PDB2E9X Β· 2.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.34LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.88 [0.59–1.34]
RankingsWhere GINS3 stands among ~20K protein-coding genes
  • #7,264of 20,598
    Most Researched64
  • #4,396of 5,498
    Most Pathogenic Variants2
  • #13,995of 17,882
    Most Constrained (LOEUF)1.34
Genes detectedGINS3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Hypomorphic GINS3 variants alter DNA replication and cause Meier-Gorlin syndrome.
PMID: 35603789
JCI Insight Β· 2022
1.00
2
Gene interaction perturbation network deciphers a high-resolution taxonomy in colorectal cancer.
PMID: 36345721
Elife Β· 2022
0.90
3
METTL14 promotes lipid metabolism reprogramming and sustains nasopharyngeal carcinoma progression via enhancing m
PMID: 39021049
Clin Transl Med Β· 2024
0.80
4
A novel prognostic biomarker:
PMID: 37304536
Transl Cancer Res Β· 2023
0.70
5
Expression of MCMs in Endometrial Cancer and its Biological Correlation Analysis.
PMID: 35792121
Comb Chem High Throughput Screen Β· 2023
0.60