GNAT2

Chr 1

G protein subunit alpha transducin 2

Also known as: ACHM4, GNATC, HG1D

GNAT2 encodes the alpha subunit of cone transducin, a G protein that couples rhodopsin to cGMP-phosphodiesterase in the phototransduction cascade of cone photoreceptors. Biallelic mutations cause achromatopsia 4, a congenital disorder characterized by complete color blindness, reduced visual acuity, and photophobia affecting cone function from birth. The gene shows very low constraint against loss-of-function variants (pLI near 0), suggesting the phenotype follows autosomal recessive inheritance.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Achromatopsia 4MIM #613856
0
Active trials
13
Pubs (1 yr)
68
P/LP submissions
8%
P/LP missense
0.98
LOEUF
LOF
Mechanism· G2P
Clinical SummaryGNAT2
🧬
Gene-Disease Validity (ClinGen)
GNAT2-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 unique Pathogenic / Likely Pathogenic· 123 VUS of 283 total submissions
📖
GeneReview available — GNAT2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.62
OE 0.59 (0.370.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.66Z-score
OE missense 0.86 (0.760.98)
161 obs / 186.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.370.98)
00.351.4
Missense OE0.86 (0.760.98)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 11 / 18.6Missense obs/exp: 161 / 186.5Syn Z: 0.02
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGNAT2-related Achromatopsia 4LOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.74top 25%
GOF
0.80top 10%
LOF
0.1994th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

283 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic12
VUS123
Likely Benign85
Benign4
Conflicting14
39
Pathogenic
12
Likely Pathogenic
123
VUS
85
Likely Benign
4
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
2
22
0
39
Likely Pathogenic
6
2
4
0
12
VUS
0
96
22
5
123
Likely Benign
0
3
34
48
85
Benign
0
1
2
1
4
Conflicting
14
Total211048454277

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

View in ClinVar →

Protein Context — Lollipop Plot

GNAT2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →