EFNA4

Chr 1

ephrin A4

Also known as: EFL4, EPLG4, LERK-4, LERK4

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 that has been implicated in proliferation and metastasis of several types of cancers. [provided by RefSeq, May 2022]

OMIMResearchGenerating clinical summary…
GOFmechanismLOEUF 1.46
Clinical SummaryEFNA4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 VUS of 56 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.46LOEUF
pLI 0.000
Z-score 0.66
OE 0.75 (0.411.46)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.76Z-score
OE missense 0.80 (0.670.95)
91 obs / 113.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.75 (0.411.46)
00.351.4
Missense OE?0.80 (0.670.95)
00.61.4
Synonymous OE?0.95
01.21.6
LoF obs/exp: 6 / 8.0Missense obs/exp: 91 / 113.8Syn Z: 0.29

This gene — mechanism propensity

DN
0.6065th %ile
GOF
0.6736th %ile
LOF
0.3453th %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

56 submitted variants in ClinVar

Classification Summary

VUS33
Likely Benign17
Benign1
33
VUS
17
Likely Benign
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
1
32
0
0
33
Likely Benign
0
5
5
7
17
Benign
0
0
1
0
1
Total1376751

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 EFNA4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

EFNA4 · 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 →