EHBP1L1

Chr 11

EH domain binding protein 1 like 1

NCBI Gene: 254102 ENSG00000173442 UniProt: Q8N3D4 OMIM: 619583

The EHBP1L1 protein functions as a Rab effector protein involved in vesicle trafficking and is predicted to regulate erythrocyte differentiation, enucleation, and mitochondrion localization. Mutations in this gene cause autosomal recessive intellectual disability with macrocephaly and seizures, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.659), affecting primarily neurological development.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable actin filament binding activity and small GTPase binding activity. Predicted to be involved in actin cytoskeleton organization and endocytic recycling. Predicted to act upstream of or within several processes, including enucleation; erythrocyte differentiation; and microvillus organization. Located in membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.000

Z-score 3.78

OE 0.49 (0.37–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.85Z-score

OE missense 0.92 (0.86–0.97)

720 obs / 786.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.37–0.66)

0≤0.351.4

Missense OE?0.92 (0.86–0.97)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 31 / 63.5Missense obs/exp: 720 / 786.8Syn Z: 0.97

Background carrier burden — how many people carry a rare variant somewhere in EHBP1L1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 26

2,105 rare PASS variants

Rare truncating (LoF)

1 in 320

345 rare PASS variants

Rare synonymous (reference)

1 in 39

931 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EHBP1L1. 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 33	1 in 350
South Asian	~43k	1 in 22	1 in 260
Remaining (unassigned)	~30k	1 in 25	1 in 350
European (Finnish)	~27k	1 in 95	1 in 770
Admixed American	~22k	1 in 21	1 in 340
African / African American	~21k	1 in 28	1 in 550
East Asian	~20k	1 in 29	1 in 380
Ashkenazi Jewish	~13k	1 in 180	1 in 880
Middle Eastern	~2,884	1 in 27	1 in 260

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 17 of 19 coding exons well covered in gnomAD exomes; exons 3, 12 marginal. Genomes: 18 of 19 (exon 17 below).? see exons ↓