EFNB1

Chr X

ephrin B1

Also known as: CFND, CFNS, EFB1, EFL3, EPLG2, Elk-L, LERK2

NCBI Gene: 1947 ENSG00000090776 UniProt: P98172

The encoded protein is a type I membrane protein that serves as a ligand for Eph-related receptor tyrosine kinases and functions in cell adhesion and nervous system development or maintenance. Loss-of-function mutations cause craniofrontonasal dysplasia, an X-linked dominant disorder. The gene is highly intolerant to loss-of-function variants, consistent with the dominant inheritance pattern.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a type I membrane protein and a ligand of Eph-related receptor tyrosine kinases. It may play a role in cell adhesion and function in the development or maintenance of the nervous system. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCraniofrontonasal syndrome

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · craniofrontonasal syndrome · XL · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.35

LOEUF· LoF intol.

LOF

Mechanism· G2P

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 — X-linked: males carry a single copy

LoF Constraint?

0.35LOEUF

pLI 0.933

Z-score 2.71

OE 0.00 (0.00–0.35)

Highly constrained

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

Missense Constraint?

1.59Z-score

OE missense 0.64 (0.55–0.76)

100 obs / 155.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.35)

0≤0.351.4

Missense OE?0.64 (0.55–0.76)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 0 / 8.6Missense obs/exp: 100 / 155.9Syn Z: 0.26

Background carrier burden — how many people carry a rare variant somewhere in EFNB1?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 280

243 rare PASS variants

Rare truncating (LoF)

1 in 730,000

1 rare PASS variants

Rare synonymous (reference)

1 in 440

142 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EFNB1. 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)	~561k	1 in 370	none seen
South Asian	~36k	1 in 300	none seen
Remaining (unassigned)	~31k	1 in 270	none seen
European (Finnish)	~27k	1 in 1,100	≈ 1 in 27,000
Admixed American	~23k	1 in 320	none seen
African / African American	~21k	1 in 490	none seen
East Asian	~20k	1 in 340	none seen
Ashkenazi Jewish	~13k	1 in 2,600	none seen
Middle Eastern	~2,758	1 in 310	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): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓