GNAI3

Chr 1AD

G protein subunit alpha i3

Also known as: 87U6, ARCND1, ARCODS, HG1A

NCBI Gene: 2773 ENSG00000065135 UniProt: P08754 OMIM: 139370

Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling pathways. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes an alpha subunit and belongs to the G-alpha family. Mutation in this gene, resulting in a gly40-to-arg substitution, is associated with auriculocondylar syndrome, and shown to affect downstream targets in the G protein-coupled endothelin receptor pathway. [provided by RefSeq, Jun 2012]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Auriculocondylar syndrome 1MIM #602483

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · auriculocondylar syndrome · AD · ClinGen 2026

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.61

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.038

Z-score 2.82

OE 0.31 (0.17–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.79Z-score

OE missense 0.64 (0.55–0.74)

122 obs / 191.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.17–0.61)

0≤0.351.4

Missense OE?0.64 (0.55–0.74)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 6 / 19.4Missense obs/exp: 122 / 191.8Syn Z: 0.33

Background carrier burden — how many people carry a rare variant somewhere in GNAI3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

391 rare PASS variants

Rare truncating (LoF)

1 in 3,900

45 rare PASS variants

Rare synonymous (reference)

1 in 430

143 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GNAI3. 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 230	1 in 3,200
South Asian	~43k	1 in 210	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 310	≈ 1 in 7,500
European (Finnish)	~27k	1 in 1,100	none seen
Admixed American	~22k	1 in 320	≈ 1 in 11,000
African / African American	~21k	1 in 150	≈ 1 in 10,000
East Asian	~20k	1 in 210	1 in 2,600
Ashkenazi Jewish	~13k	1 in 750	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 170	≈ 1 in 1,400

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): 6 of 8 coding exons well covered in gnomAD exomes; exons 5, 7 marginal. Genomes: all 8.? see exons ↓