CACNG8

Chr 19

calcium voltage-gated channel auxiliary subunit gamma 8

The encoded protein is a transmembrane AMPA receptor regulatory protein (TARP) that regulates trafficking and gating properties of AMPA-selective glutamate receptors and modulates L-type calcium channel activity. Mutations cause early-onset epileptic encephalopathy with severe developmental delays and intellectual disability, following an autosomal recessive inheritance pattern. This gene is highly constrained against loss-of-function variants, indicating critical importance for normal neurodevelopment.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.29
Clinical SummaryCACNG8
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.964
Z-score 2.98
OE 0.00 (0.000.29)
Highly constrained

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

Missense Constraint
2.34Z-score
OE missense 0.50 (0.420.60)
89 obs / 176.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.29)
00.351.4
Missense OE0.50 (0.420.60)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 0 / 10.3Missense obs/exp: 89 / 176.3Syn Z: -0.05
DN
0.5280th %ile
GOF
0.6248th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CACNG8 · 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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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC