CACNG5

Chr 17

calcium voltage-gated channel auxiliary subunit gamma 5

NCBI Gene: 27091 ENSG00000075429 UniProt: Q9UF02 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a type II 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 I TARP and a calcium channel gamma subunit. This gene is a susceptibility locus for schizophrenia and bipolar disorder. [provided by RefSeq, Dec 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.03

LOEUF

Multiple*

Mechanism· predicted

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 OE?0.49 (0.26–1.03)

0≤0.351.4

Missense OE?0.95 (0.84–1.08)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 5 / 10.2Missense obs/exp: 171 / 180.1Syn Z: -0.17

Background carrier burden — how many people carry a rare variant somewhere in CACNG5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

386 rare PASS variants

Rare truncating (LoF)

1 in 4,300

49 rare PASS variants

Rare synonymous (reference)

1 in 300

166 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CACNG5. 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 140	1 in 4,100
South Asian	~43k	1 in 190	1 in 2,000
Remaining (unassigned)	~30k	1 in 87	≈ 1 in 15,000
European (Finnish)	~27k	1 in 300	≈ 1 in 21,000
Admixed American	~22k	1 in 95	1 in 1,400
African / African American	~21k	1 in 120	≈ 1 in 21,000
East Asian	~20k	1 in 81	1 in 3,300
Ashkenazi Jewish	~13k	1 in 1,500	none seen
Middle Eastern	~2,884	1 in 120	none seen

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓