CACNG2

Chr 22AD

calcium voltage-gated channel auxiliary subunit gamma 2

Also known as: MRD10

NCBI Gene: 10369 ENSG00000166862 UniProt: Q9Y698 OMIM: 602911

CACNG2 encodes a transmembrane AMPA receptor regulatory protein (TARP) that controls trafficking and gating properties of AMPA-selective glutamate receptors, which mediate fast excitatory neurotransmission and are crucial for synaptic plasticity, learning and memory. Mutations cause autosomal dominant intellectual developmental disorder. This gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.38), suggesting intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, OMIM, 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. The AMPA subtype of ionotropic glutamate receptors are ligand gated ion channels that are typically activated by glutamate released from presynaptic neuron terminals and mediate fast neurotransmission in excitatory synapses. TARPs thus play an important role in synaptic plasticity, learning and memory. Mutations in this gene cause an autosomal dominant form of cognitive disability. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Intellectual developmental disorder, autosomal dominant 10MIM #614256

Clinical highlights

Gene–disease validity (ClinGen)

Limited · complex neurodevelopmental disorder · AD · ClinGen 2026

not for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.38

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.923

Z-score 3.03

OE 0.08 (0.03–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.09Z-score

OE missense 0.59 (0.51–0.68)

119 obs / 202.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.38)

0≤0.351.4

Missense OE?0.59 (0.51–0.68)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 1 / 12.6Missense obs/exp: 119 / 202.9Syn Z: -0.07

Background carrier burden — how many people carry a rare variant somewhere in CACNG2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

366 rare PASS variants

Rare truncating (LoF)

1 in 20,000

9 rare PASS variants

Rare synonymous (reference)

1 in 350

176 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CACNG2. 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 300	≈ 1 in 140,000
South Asian	~43k	1 in 180	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 340	none seen
European (Finnish)	~27k	1 in 1,000	≈ 1 in 27,000
Admixed American	~22k	1 in 400	none seen
African / African American	~21k	1 in 470	≈ 1 in 6,900
East Asian	~20k	1 in 240	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 2,600	none seen
Middle Eastern	~2,884	≈ 1 in 580	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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓