EPHB1

Chr 3

EPH receptor B1

Also known as: ELK, EPHT2, Hek6, NET

NCBI Gene: 2047 ENSG00000154928 UniProt: P54762 OMIM: 600600

Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. 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 divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene is a receptor for ephrin-B family members. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.26

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.998

Z-score 5.21

OE 0.12 (0.06–0.26)

Highly constrained

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

Missense Constraint?

2.36Z-score

OE missense 0.73 (0.68–0.79)

444 obs / 607.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.06–0.26)

0≤0.351.4

Missense OE?0.73 (0.68–0.79)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 5 / 41.0Missense obs/exp: 444 / 607.9Syn Z: -1.66

Background carrier burden — how many people carry a rare variant somewhere in EPHB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 55

1,237 rare PASS variants

Rare truncating (LoF)

1 in 2,100

98 rare PASS variants

Rare synonymous (reference)

1 in 59

572 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EPHB1. 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 52	1 in 2,700
South Asian	~43k	1 in 54	1 in 1,300
Remaining (unassigned)	~30k	1 in 55	1 in 2,000
European (Finnish)	~27k	1 in 140	1 in 5,300
Admixed American	~22k	1 in 64	1 in 2,500
African / African American	~21k	1 in 51	1 in 1,400
East Asian	~20k	1 in 50	1 in 1,200
Ashkenazi Jewish	~13k	1 in 200	1 in 1,400
Middle Eastern	~2,884	1 in 62	≈ 1 in 1,400

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): All 16 coding exons well covered in gnomAD exomes and genomes.? see exons ↓