EFNA3

Chr 1

ephrin A3

Also known as: EFL2, EPLG3, Ehk1-L, LERK3

This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNA class ephrin. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.80
Clinical SummaryEFNA3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
29 VUS of 35 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.80LOEUF
pLI 0.126
Z-score 1.99
OE 0.31 (0.140.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.75Z-score
OE missense 0.81 (0.690.96)
101 obs / 124.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.31 (0.140.80)
00.351.4
Missense OE?0.81 (0.690.96)
00.61.4
Synonymous OE?0.97
01.21.6
LoF obs/exp: 3 / 9.7Missense obs/exp: 101 / 124.5Syn Z: 0.17

This gene — mechanism propensity

DN
0.6358th %ile
GOF
0.6833th %ile
LOF
0.4037th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction 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

35 submitted variants in ClinVar

Classification Summary

VUS29
Benign1
29
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
29
0
0
29
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total0290130

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap EFNA3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

EFNA3 · 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 →