EHD2

Chr 19

EH domain containing 2

Also known as: PAST2

NCBI Gene: 30846ENSG00000024422UniProt: Q9NZN4

This gene encodes a member of the EH domain-containing protein family. These proteins are characterized by a C-terminal EF-hand domain, a nucleotide-binding consensus site at the N terminus and a bipartite nuclear localization signal. The encoded protein interacts with the actin cytoskeleton through an N-terminal domain and also binds to an EH domain-binding protein through the C-terminal EH domain. This interaction appears to connect clathrin-dependent endocytosis to actin, suggesting that this gene product participates in the endocytic pathway. [provided by RefSeq, Jul 2008]

105
ClinVar variants
12
Pathogenic / LP
0.31
pLI score
0
Active trials
Clinical Summary— EHD2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 91 VUS of 105 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.54LOEUF
pLI 0.308
Z-score 2.92
OE 0.23 (0.12–0.54)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.88Z-score
OE missense 0.73 (0.66–0.80)
269 obs / 371.0 exp
Tolerant

Mild missense constraint

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.0.23 (0.12–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.66–0.80)
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.0.95
0≤1.21.6
LoF obs/exp: 4 / 17.0Missense obs/exp: 269 / 371.0Syn Z: 0.50

ClinVar Variant Classifications

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS91
Likely Benign2
9
Pathogenic
3
Likely Pathogenic
91
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
3
0
3
VUS
0
84
7
0
91
Likely Benign
0
0
1
1
2
Benign
0
0
0
0
0
Total084201105

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

View in ClinVar →

Protein Context — Lollipop Plot

EHD2 · 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
The missing link: ARID1B non-truncating variants causing Coffin-Siris syndrome due to protein aggregation.
Bosch E et al.·Hum Genet
2024
EHD2-mediated restriction of caveolar dynamics regulates cellular fatty acid uptake.
Matthaeus C et al.·Proc Natl Acad Sci U S A
2020
EHD2 Overexpression Suppresses the Proliferation, Migration, and Invasion in Human Colon Cancer.
Guan C et al.·Cancer Invest
2021
Prognostic implication of histological features associated with EHD2 expression in papillary thyroid carcinoma.
Kim Y et al.·PLoS One
2017
Effect of EH domain containing protein 2 on the biological behavior of clear cell renal cell carcinoma.
Liu C et al.·Hum Exp Toxicol
2019
[Low expressions of EHD2 and E-cadherin correlate with a poor prognosis for clear cell renal cell carcinoma].
Ye M et al.·Zhong Nan Da Xue Xue Bao Yi Xue Ban
2019
Superior Properties of Fc-comprising scTRAIL Fusion Proteins.
Hutt M et al.·Mol Cancer Ther
2017
Correlation of histopathologic characteristics to protein expression and function in malignant melanoma.
Welinder C et al.·PLoS One
2017
Identification of a mesenchymal-related signature associated with clinical prognosis in glioma.
Zhang Z et al.·Aging (Albany NY)
2021
Integrative radiogenomic analysis for genomic signatures in glioblastomas presenting leptomeningeal dissemination.
You HJ et al.·Medicine (Baltimore)
2016
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