EPHA4

Chr 2

EPH receptor A4

Also known as: EK8, HEK8, SEK, TYRO1

NCBI Gene: 2043 ENSG00000116106 UniProt: P54764 OMIM: 602188

EPHA4 encodes a receptor tyrosine kinase that binds ephrin ligands and regulates axonal guidance, synaptic plasticity, and nervous system development through control of cell adhesion and morphology. Mutations cause autosomal dominant amyotrophic lateral sclerosis and autosomal recessive developmental and epileptic encephalopathy with microcephaly. This gene is highly constrained against loss-of-function variation, indicating that EPHA4 function is essential for normal development.

OMIM ResearchSummary from RefSeq, UniProt

This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in EPHA4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 93

991 rare PASS variants

Rare truncating (LoF)

1 in 4,500

57 rare PASS variants

Rare synonymous (reference)

1 in 75

482 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EPHA4. 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 120	1 in 4,700
South Asian	~43k	1 in 73	none seen
Remaining (unassigned)	~30k	1 in 97	1 in 2,100
European (Finnish)	~27k	1 in 200	1 in 2,900
Admixed American	~22k	1 in 63	1 in 1,400
African / African American	~21k	1 in 73	≈ 1 in 5,900
East Asian	~20k	1 in 130	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 210	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 120	none seen

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): 16 of 17 coding exons well covered in gnomAD exomes; exon 9 marginal. Genomes: all 17.? see exons ↓