CNIH3

Chr 1ARAD

cornichon family AMPA receptor auxiliary protein 3

Also known as: CNIH-3

NCBI Gene: 149111ENSG00000143786UniProt: Q8TBE1

Predicted to enable channel regulator activity and signaling receptor binding activity. Involved in regulation of AMPA receptor activity. Predicted to be located in dendritic shaft and postsynaptic membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in dendrite and glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2025]

Primary Disease Associations & Inheritance

?Intellectual developmental disorder, autosomal recessive 76MIM #619931
AR
Intellectual developmental disorder, autosomal dominant 67MIM #619927
AD
61
ClinVar variants
32
Pathogenic / LP
0.85
pLI score
0
Active trials
Clinical Summary— CNIH3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 27 VUS of 61 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.45LOEUF
pLI 0.845
Z-score 2.72
OE 0.10 (0.03–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.68Z-score
OE missense 0.80 (0.66–0.97)
72 obs / 90.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.10 (0.03–0.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.66–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.73
0≤1.21.6
LoF obs/exp: 1 / 10.5Missense obs/exp: 72 / 90.3Syn Z: 1.28

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
VUS27
Benign2
32
Pathogenic
27
VUS
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
0
0
0
VUS
0
19
8
0
27
Likely Benign
0
0
0
0
0
Benign
0
1
0
1
2
Total02040161

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CNIH3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

3 OMIM entries

OMIM

?Intellectual developmental disorder, autosomal recessive 76

MIM #619931

Molecular basis of disorder known

Autosomal recessive

Intellectual developmental disorder, autosomal dominant 67

MIM #619927

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools