CACNG6

Chr 19

calcium voltage-gated channel auxiliary subunit gamma 6

This protein regulates L-type calcium channels and AMPA glutamate receptors by modulating their trafficking to synapses and gating properties. The gene is not well-established as a cause of pediatric neurological disease, though variants have been associated with aspirin-intolerant asthma. The gene shows low constraint against loss-of-function variants, suggesting haploinsufficiency is likely tolerated.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.69
Clinical SummaryCACNG6
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.69LOEUF
pLI 0.000
Z-score 0.14
OE 0.94 (0.531.69)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.32Z-score
OE missense 0.92 (0.791.07)
120 obs / 130.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.94 (0.531.69)
00.351.4
Missense OE0.92 (0.791.07)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 7 / 7.4Missense obs/exp: 120 / 130.2Syn Z: 0.93
DN
0.6551th %ile
GOF
0.6638th %ile
LOF
0.3453th %ile

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

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CACNG6 · 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

No active trials found for this gene.

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