CACNG1

Chr 17

calcium voltage-gated channel auxiliary subunit gamma 1

Also known as: CACNLG

NCBI Gene: 786 ENSG00000108878 UniProt: Q06432 OMIM: 114209

The gamma-1 subunit regulates voltage-gated calcium channels that produce L-type calcium currents in skeletal muscle and controls channel inactivation kinetics during excitation-contraction coupling. Mutations cause congenital myasthenic syndrome with autosomal recessive inheritance. This gene is extremely tolerant to loss-of-function variants, indicating that pathogenic mutations likely affect protein function through other mechanisms.

OMIM ResearchSummary from RefSeq, UniProt

Voltage-dependent calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma, and is one of two known gamma subunit proteins. This particular gamma subunit is part of skeletal muscle 1,4-dihydropyridine-sensitive calcium channels and is an integral membrane protein that plays a role in excitation-contraction coupling. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two family members that function as transmembrane AMPA receptor regulatory proteins (TARPs). [provided by RefSeq, Dec 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.82

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.82LOEUF

pLI 0.000

Z-score -0.54

OE 1.19 (0.74–1.82)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.32Z-score

OE missense 0.93 (0.81–1.07)

141 obs / 152.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.19 (0.74–1.82)

0≤0.351.4

Missense OE?0.93 (0.81–1.07)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 11 / 9.2Missense obs/exp: 141 / 152.2Syn Z: -0.22

Background carrier burden — how many people carry a rare variant somewhere in CACNG1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

302 rare PASS variants

Rare truncating (LoF)

1 in 2,000

46 rare PASS variants

Rare synonymous (reference)

1 in 200

134 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CACNG1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 4,000
South Asian	~43k	1 in 110	1 in 4,800
Remaining (unassigned)	~30k	1 in 140	1 in 3,800
European (Finnish)	~27k	1 in 490	≈ 1 in 8,100
Admixed American	~22k	1 in 210	1 in 2,100
African / African American	~21k	1 in 130	1 in 2,100
East Asian	~20k	1 in 260	1 in 770
Ashkenazi Jewish	~13k	1 in 1,600	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓