GJB5

Chr 1

gap junction protein beta 5

Also known as: CX31.1

NCBI Gene: 2709ENSG00000189280UniProt: O95377

This gene encodes a member of the beta-type (group I) connexin family. The encoded protein is a gap junction protein involved in intercellular communication related to epidermal differentiation and environmental sensing. This gene has been linked to non-small cell lung cancer. [provided by RefSeq, Nov 2012]

54
ClinVar variants
9
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GJB5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 42 VUS of 54 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.
1.82LOEUF
pLI 0.000
Z-score -0.25
OE 1.11 (0.62–1.82)
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.
0.05Z-score
OE missense 0.99 (0.87–1.13)
164 obs / 165.8 exp
Tolerant

Mild missense constraint

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.1.11 (0.62–1.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.87–1.13)
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.1.03
0≤1.21.6
LoF obs/exp: 7 / 6.3Missense obs/exp: 164 / 165.8Syn Z: -0.21

ClinVar Variant Classifications

54 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS42
Likely Benign3
7
Pathogenic
2
Likely Pathogenic
42
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
38
4
0
42
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total04113054

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

View in ClinVar →

Protein Context — Lollipop Plot

GJB5 · 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
Pan-cancer analysis of GJB5 as a novel prognostic and immunological biomarker.
Yang X et al.·Sci Rep
2025
Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis.
Richard G et al.·Nat Genet
1998
Gap junction protein beta 5 interacts with Gαi3 to promote Akt activation and cervical cancer cell growth.
Li P et al.·Cell Death Dis
2025
DDR1 as a key prognostic biomarker in non-small cell lung cancer: identification, validation, and potential therapeutic implications.
Lu R et al.·Front Immunol
2025
GJB5 association with BRAF mutation and survival in cutaneous malignant melanoma.
Scatolini M et al.·Br J Dermatol
2022
The A818-6 system as an in-vitro model for studying the role of the transportome in pancreatic cancer.
Tawfik D et al.·BMC Cancer
2020Functional
BMP4 and PHLDA1 are plausible drug-targetable candidate genes for KRAS G12A-, G12D-, and G12V-driven colorectal cancer.
Ohnami S et al.·Mol Cell Biochem
2021
RNA sequencing of sessile serrated colon polyps identifies differentially expressed genes and immunohistochemical markers.
Delker DA et al.·PLoS One
2014
Connexin mutations in Brazilian patients with skin disorders with or without hearing loss.
Alexandrino F et al.·Am J Med Genet A
2009Cohort
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