CACNG4

Chr 17

calcium voltage-gated channel auxiliary subunit gamma 4

NCBI Gene: 27092 ENSG00000075461 UniProt: Q9UBN1 OMIM: 606404

CACNG4 encodes a transmembrane AMPA receptor regulatory protein (TARP) that regulates trafficking and gating of AMPA-selective glutamate receptors and modulates L-type calcium channel activity. The gene shows low constraint against loss-of-function variants (LOEUF 0.825), suggesting tolerance to such mutations. No established disease associations are currently documented for CACNG4 mutations.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a type I transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. 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, a type II TARP and a calcium channel gamma subunit. [provided by RefSeq, Dec 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.017

Z-score 2.01

OE 0.39 (0.20–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.82Z-score

OE missense 0.65 (0.56–0.75)

138 obs / 212.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.20–0.82)

0≤0.351.4

Missense OE?0.65 (0.56–0.75)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 5 / 12.7Missense obs/exp: 138 / 212.9Syn Z: -0.11

Background carrier burden — how many people carry a rare variant somewhere in CACNG4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

378 rare PASS variants

Rare truncating (LoF)

1 in 6,100

28 rare PASS variants

Rare synonymous (reference)

1 in 130

200 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CACNG4. 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 290	1 in 6,700
South Asian	~43k	1 in 130	1 in 7,100
Remaining (unassigned)	~30k	1 in 180	≈ 1 in 12,000
European (Finnish)	~27k	1 in 340	1 in 3,700
Admixed American	~22k	1 in 160	≈ 1 in 5,200
African / African American	~21k	1 in 320	1 in 3,200
East Asian	~20k	1 in 290	≈ 1 in 5,500
Ashkenazi Jewish	~13k	1 in 520	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 120	≈ 1 in 2,100

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): 4 of 4 coding exons well covered in gnomAD exomes. Genomes: 3 of 4 (exon 1 below).? see exons ↓