EHD4

protein-coding

EH domain containing 4, the group of EF-hand domain containing

Gene summary

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]

Previous symbols:

PAST4

MANE transcript

NM_139265.4

Inheritance

—

ClinVar variants

U:87B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr15:41,895,933-41,972,557

External References & Databases

Ensembl (ENSG00000103966)

Transcript & Mutation Effects

hg38 • Region Span ~76.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EHD4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 83

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_139265.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			84 clinvar	2 clinvar		86
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	87	2	0	89

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_139265.4	RefSeq	NP_644670.1	6	MANE Select
ENST00000220325.9	Ensembl	ENSP00000220325.4	6	MANE Select
ENST00000857506.1	Ensembl	ENSP00000527565.1	7	Standard
ENST00000857506.2	Ensembl	ENSP00000527565.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Neurotrophic factor-mediated Trk receptor signaling

Biological Process

pinocytosis
regulation of endocytosis
endocytic recycling
positive regulation of peptidyl-tyrosine phosphorylation
protein homooligomerization

Molecular Function

nucleic acid binding
calcium ion binding
protein binding
ATP binding
GTP binding

Cellular Component

nucleus
endoplasmic reticulum
plasma membrane
membrane
early endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000220325
Coding exons: 6
Length: 73827
Individuals with no LoFs: 125696
Homozygous LoFs: 0
Heterozygous LoFs: 52
Defined: 125748
p: 0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.55	262	343	0.764	0.0000209	3551
Missense (PolyPhen)		125	180.16	0.69384		1873
Synonymous	0.597	154	164	0.941	0.0000120	1055
Loss of Function	2.34	11	23.1	0.476	0.00000130	236

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.00076	0.00069	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00037	0.00033	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000099	0.000097	rare
South Asian	0.00020	0.00020	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: ATP- and membrane-binding protein that probably controls membrane reorganization/tubulation upon ATP hydrolysis. Plays a role in early endosomal transport. {ECO:0000269|PubMed:17233914, ECO:0000269|PubMed:18331452}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.280
RVIS EVS: -0.75
RVIS percentile EVS: 13.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.702

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium