EFNA5

Chr 5

ephrin A5

Also known as: AF1, EFL5, EPLG7, GLC1M, LERK7, RAGS

NCBI Gene: 1946 ENSG00000184349 UniProt: P52803

Ephrin-A5 is a GPI-anchored cell surface ligand that binds to EphA receptors to mediate bidirectional signaling essential for neuronal migration, axon guidance, and cell-cell adhesion during brain development. The gene is highly intolerant to loss-of-function variants (pLI=0.96), but no specific human disease has been definitively associated with EFNA5 mutations. Based on its critical role in neural development and extreme constraint against variation, mutations would likely cause neurodevelopmental disorders with an autosomal dominant inheritance pattern.

ResearchSummary from RefSeq, UniProt

Ephrin-A5, a member of the ephrin gene family, prevents axon bundling in cocultures of cortical neurons with astrocytes, a model of late stage nervous system development and differentiation. The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, particularly in the nervous system. EPH receptors typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin ligands and receptors have been named by the Eph Nomenclature Committee (1997). 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. The Eph family of receptors are similarly divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOEUF 0.30

Clinical Summary— EFNA5

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

16 VUS of 28 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.961

Z-score 2.94

OE 0.00 (0.00–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.52Z-score

OE missense 0.63 (0.53–0.76)

84 obs / 133.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.30)

0≤0.351.4

Missense OE?0.63 (0.53–0.76)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 0 / 10.1Missense obs/exp: 84 / 133.2Syn Z: -0.17

ClinVar Variant Classifications

28 submitted variants in ClinVar

ClinVar

Classification Summary

VUS16

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	16	0	16
Likely Benign	0	1	1
Benign	0	0	0
Total	16	1	17

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap EFNA5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →