EHD4

Chr 15

EH domain containing 4

Also known as: PAST4

NCBI Gene: 30844 ENSG00000103966 UniProt: Q9H223 OMIM: 605892

Enables cadherin binding activity. Involved in endocytic recycling and protein homooligomerization. Located in endoplasmic reticulum and recycling endosome membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.79

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.000

Z-score 2.34

OE 0.48 (0.30–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.55Z-score

OE missense 0.76 (0.69–0.85)

262 obs / 342.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.30–0.79)

0≤0.351.4

Missense OE?0.76 (0.69–0.85)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 11 / 23.1Missense obs/exp: 262 / 342.7Syn Z: 0.60

Background carrier burden — how many people carry a rare variant somewhere in EHD4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

684 rare PASS variants

Rare truncating (LoF)

1 in 2,200

85 rare PASS variants

Rare synonymous (reference)

1 in 130

315 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EHD4. 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 130	1 in 2,300
South Asian	~43k	1 in 74	1 in 1,100
Remaining (unassigned)	~30k	1 in 78	1 in 5,900
European (Finnish)	~27k	1 in 380	1 in 1,300
Admixed American	~22k	1 in 76	1 in 730
African / African American	~21k	1 in 82	1 in 1,500
East Asian	~20k	1 in 64	1 in 880
Ashkenazi Jewish	~13k	1 in 710	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 77	≈ 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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓