CNIH2

Chr 11

cornichon family AMPA receptor auxiliary protein 2

Also known as: CNIH-2, Cnil

NCBI Gene: 254263 ENSG00000174871 UniProt: Q6PI25

The encoded protein is an auxiliary subunit that regulates AMPA glutamate receptor trafficking to synapses and modulates receptor gating properties including activation, deactivation and desensitization. Mutations cause autosomal recessive intellectual disability with seizures and microcephaly. This gene is highly constrained against loss-of-function variants (pLI 0.95), indicating that such variants are likely to be pathogenic.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is an auxiliary subunit of the ionotropic glutamate receptor of the AMPA subtype. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system. This protein has been reported to interact with the Type I AMPA receptor regulatory protein isoform gamma-8 to control assembly of hippocampal AMPA receptor complexes, thereby modulating receptor gating and pharmacology. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ResearchGenerating clinical summary…

Clinical highlights

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

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P/LP missense

0.31

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.952

Z-score 2.86

OE 0.00 (0.00–0.31)

Highly constrained

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

Missense Constraint?

2.25Z-score

OE missense 0.33 (0.24–0.45)

29 obs / 88.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.31)

0≤0.351.4

Missense OE?0.33 (0.24–0.45)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 0 / 9.5Missense obs/exp: 29 / 88.6Syn Z: 0.99

Background carrier burden — how many people carry a rare variant somewhere in CNIH2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,900

116 rare PASS variants

Rare truncating (LoF)

1 in 59,000

12 rare PASS variants

Rare synonymous (reference)

1 in 330

76 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CNIH2. 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 1,900	1 in 79,000
South Asian	~43k	1 in 2,200	≈ 1 in 9,700
Remaining (unassigned)	~30k	1 in 370	none seen
European (Finnish)	~27k	≈ 1 in 24,000	≈ 1 in 19,000
Admixed American	~22k	1 in 1,500	none seen
African / African American	~21k	1 in 2,200	none seen
East Asian	~20k	1 in 1,600	none seen
Ashkenazi Jewish	~13k	1 in 930	none seen
Middle Eastern	~2,884	≈ 1 in 960	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): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓