EFR3A

Chr 8

EFR3 homolog A

NCBI Gene: 23167 ENSG00000132294 UniProt: Q14156 OMIM: 611798

EFR3A encodes a membrane-anchoring protein that localizes phosphatidylinositol 4-kinase to the plasma membrane and regulates phosphatidylinositol 4-phosphate synthesis, while also affecting G-protein-coupled receptor responsiveness. Mutations cause autism spectrum disorders with autosomal inheritance patterns. The gene is highly intolerant to loss-of-function variants, suggesting that even heterozygous mutations can cause disease.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is part of a complex that plays a role in maintaining an active pool of phosphatidylinositol 4-kinase (PI4K) at the plasma membrane. This protein is thought to be a peripheral membrane protein that associates with the plasma membrane through palmitoylation. Studies indicate that this gene product plays a role in controlling G protein-coupled receptor (GPCR) activity by affecting receptor phosphorylation. Whole exome sequencing studies have implicated mutations in this gene with autism spectrum disorders. [provided by RefSeq, Apr 2016]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.77

Clinical Summary— EFR3A

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

105 VUS of 159 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.000

Z-score 2.78

OE 0.55 (0.40–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.80Z-score

OE missense 0.89 (0.82–0.97)

376 obs / 422.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.40–0.77)

0≤0.351.4

Missense OE?0.89 (0.82–0.97)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 24 / 43.9Missense obs/exp: 376 / 422.0Syn Z: -0.17

This gene — mechanism propensity

0.6065th %ile

GOF

0.6833th %ile

LOF

0.3939th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

159 submitted variants in ClinVar

ClinVar

Classification Summary

VUS105

Likely Benign16

Benign9

105

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	104	0	0	105
Likely Benign	0	6	1	9	16
Benign	0	4	4	1	9
Total	1	114	5	10	130

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

View in ClinVar →

55 pathogenic / likely-pathogenic (of 69) ClinVar copy-number / structural variants overlap EFR3A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →