CACNG5

Chr 17

calcium voltage-gated channel auxiliary subunit gamma 5

NCBI Gene: 27091ENSG00000075429UniProt: Q9UF02OMIM: 606405

The protein encoded by CACNG5 is a transmembrane AMPA receptor regulatory protein (TARP) that regulates the trafficking and gating properties of AMPA-selective glutamate receptors, particularly GRIA1, GRIA4, and GRIA2. This gene has been identified as a susceptibility locus for schizophrenia and bipolar disorder. The gene shows tolerance to loss-of-function variants (pLI 0.006, LOEUF 1.03), suggesting that complete loss of function may not be highly pathogenic.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.03
Clinical Summary— CACNG5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 51 VUS of 63 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.006
Z-score 1.51
OE 0.49 (0.26–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.24Z-score
OE missense 0.95 (0.84–1.08)
171 obs / 180.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.26–1.03)
0≤0.351.4
Missense OE0.95 (0.84–1.08)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 5 / 10.2Missense obs/exp: 171 / 180.1Syn Z: -0.17
DN
0.75top 25%
GOF
0.75top 25%
LOF
0.2968th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

63 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS51
Benign1
10
Pathogenic
1
Likely Pathogenic
51
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
50
1
0
51
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total05012163

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

View in ClinVar →

Protein Context — Lollipop Plot

CACNG5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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