EHD1

Chr 11

EH domain containing 1

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

NCBI Gene: 10938ENSG00000110047UniProt: Q9H4M9

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]

94
ClinVar variants
8
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— EHD1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 65 VUS of 94 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.61–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 1 / 16.9Missense obs/exp: 238 / 348.2Syn Z: -0.07

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS65
Likely Benign6
Benign7
6
Pathogenic
2
Likely Pathogenic
65
VUS
6
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
60
5
0
65
Likely Benign
0
0
0
6
6
Benign
0
0
3
4
7
Total060161086

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EHD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
EHD1 and RUSC2 Control Basal Epidermal Growth Factor Receptor Cell Surface Expression and Recycling.
Tom EC et al.·Mol Cell Biol
2020
A Founder Mutation in EHD1 Presents with Tubular Proteinuria and Deafness.
Issler N et al.·J Am Soc Nephrol
2022
A novel EHD1/CD44/Hippo/SP1 positive feedback loop potentiates stemness and metastasis in lung adenocarcinoma.
Liu Y et al.·Clin Transl Med
2022
Rabenosyn-5 and EHD1 interact and sequentially regulate protein recycling to the plasma membrane.
Naslavsky N et al.·Mol Biol Cell
2004
NF-κB-driven improvement of EHD1 contributes to erlotinib resistance in EGFR-mutant lung cancers.
Wang X et al.·Cell Death Dis
2018
EHD1 impaired decidualization of endometrial stromal cells in recurrent implantation failure: role of SENP1 in modulating progesterone receptor signalling†.
Zhang H et al.·Biol Reprod
2024
Epstein-Barr virus (EBV) infection of endothelial cells via endocytosis is associated with a poor prognosis in nasopharyngeal carcinoma.
Chen X-l et al.·Microbiol Spectr
2025
Increased EHD1 in trophoblasts causes RSM by activating TGFβ signaling†.
Wu X et al.·Biol Reprod
2024
Neutrophil Transcriptional Deregulation by the Periodontal Pathogen Fusobacterium nucleatum in Gastric Cancer: A Bioinformatic Study.
Zhou T et al.·Dis Markers
2022
Genetic and transcriptional landscape of plasma cells in POEMS syndrome.
Nagao Y et al.·Leukemia
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools