EHD1

Chr 11

EH domain containing 1

Also known as: H-PAST, HPAST1, PAST, PAST1

NCBI Gene: 10938 ENSG00000110047 UniProt: Q9H4M9

EHD1 encodes an ATP- and membrane-binding protein that controls membrane reorganization, endocytic trafficking, and cilium biogenesis, including formation of the ciliary vesicle and recruitment of transition zone proteins. Mutations cause neurodevelopmental disorder with spastic diplegia and visual defects, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.98), reflecting its essential cellular functions.

GeneReviews ResearchSummary from RefSeq, UniProt

This gene belongs to a highly conserved gene family encoding EPS15 homology (EH) domain-containing proteins. The protein-binding EH domain was first noted in EPS15, a substrate for the epidermal growth factor receptor. The EH domain has been shown to be an important motif in proteins involved in protein-protein interactions and in intracellular sorting. The protein encoded by this gene is thought to play a role in the endocytosis of IGF1 receptors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

GeneReviews 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)

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P/LP submissions

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P/LP missense

0.28

LOEUF· LoF intol.

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Mechanism

📖

GeneReview available — EHD1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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?

0.28LOEUF

pLI 0.983

Z-score 3.58

OE 0.06 (0.02–0.28)

Highly constrained

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

Missense Constraint?

2.10Z-score

OE missense 0.68 (0.61–0.76)

238 obs / 348.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.28)

0≤0.351.4

Missense OE?0.68 (0.61–0.76)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 1 / 16.9Missense obs/exp: 238 / 348.2Syn Z: -0.07

Background carrier burden — how many people carry a rare variant somewhere in EHD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

591 rare PASS variants

Rare truncating (LoF)

1 in 1,200

75 rare PASS variants

Rare synonymous (reference)

1 in 96

344 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EHD1. 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 150	1 in 1,100
South Asian	~43k	1 in 220	1 in 3,200
Remaining (unassigned)	~30k	1 in 120	1 in 2,300
European (Finnish)	~27k	1 in 240	≈ 1 in 8,800
Admixed American	~22k	1 in 130	≈ 1 in 6,400
African / African American	~21k	1 in 170	≈ 1 in 4,900
East Asian	~20k	1 in 150	1 in 430
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 120	≈ 1 in 2,900

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 ↓