GJC1

Chr 17

gap junction protein gamma 1

Also known as: CX45, GJA7

NCBI Gene: 10052ENSG00000182963UniProt: P36383

This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Alternatively spliced transcript variants encoding the same isoform have been described. [provided by RefSeq, Jul 2008]

44
ClinVar variants
9
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GJC1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 30 VUS of 44 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.22LOEUF
pLI 0.988
Z-score 3.38
OE 0.00 (0.00–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.07Z-score
OE missense 0.61 (0.53–0.70)
135 obs / 221.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.00 (0.00–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.53–0.70)
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.0.96
0≤1.21.6
LoF obs/exp: 0 / 13.3Missense obs/exp: 135 / 221.9Syn Z: 0.31

ClinVar Variant Classifications

44 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
VUS30
Likely Benign2
Benign3
9
Pathogenic
30
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
0
0
0
VUS
0
29
1
0
30
Likely Benign
0
2
0
0
2
Benign
0
0
1
2
3
Total03111244

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

View in ClinVar →

Protein Context — Lollipop Plot

GJC1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The expanding phenotypes of cohesinopathies: one ring to rule them all!
Piché J et al.·Cell Cycle
2019Review
Connexin45 (GJC1) loss-of-function mutation contributes to familial atrial fibrillation and conduction disease.
Li RG et al.·Heart Rhythm
2021
Mechanistic insights into super-enhancer-related genes as prognostic signatures in colon cancer.
Tang Y et al.·Aging (Albany NY)
2024
Quantitative validation of GJC1 promoter hypermethylation in benign and malignant colorectal tumors.
Ahmed D et al.·Endocr Relat Cancer
2011
A systematic review and in silico study of potential genetic markers implicated in cases of overactive bladder.
Isali I et al.·Am J Obstet Gynecol
2023Review
Original Research: A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease.
Liu L et al.·Exp Biol Med (Maywood)
2016
Significance of Aneuploidy in Predicting Prognosis and Treatment Response of Uveal Melanoma.
Zhang X et al.·Curr Med Chem
2025
Application of a co‑expression network for the analysis of aggressive and non‑aggressive breast cancer cell lines to predict the clinical outcome of patients.
Guo L et al.·Mol Med Rep
2017Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools