EEA1

protein-coding

early endosome antigen 1, the group of Zinc fingers FYVE-type

Gene summary

Enables 1-phosphatidylinositol binding activity; GTP-dependent protein binding activity; and protein homodimerization activity. Involved in endocytosis and vesicle fusion. Located in cytosol and early endosome membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_003566.4

Inheritance

—

ClinVar variants

U:156B:9

Top phenotype

Congenital portosystemic shunt

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr12:92,770,637-92,929,331

External References & Databases

Ensembl (ENSG00000102189)

Transcript & Mutation Effects

hg38 • Region Span ~158.7 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 EEA1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 146

not providedTotal: 8

Congenital portosystemic shuntTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003566.4. 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 clinvar	2
missense			143 clinvar	7 clinvar	1 clinvar	151
nonsense			1 clinvar			1
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	156	7	2	165

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003566.4	RefSeq	NP_003557.3	29	MANE Select
ENST00000322349.13	Ensembl	ENSP00000317955.8	29	MANE Select
ENST00000418984.7	Ensembl	ENSP00000394312.3	3	Standard
ENST00000549790.1	Ensembl	ENSP00000446785.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Phagosome - Homo sapiens (human)
Tuberculosis - Homo sapiens (human)
VEGFA-VEGFR2 Signaling Pathway
phosphoinositides and their downstream targets

Biological Process

endocytosis
vesicle fusion
synaptic vesicle to endosome fusion
viral RNA genome replication
early endosome to late endosome transport

Molecular Function

nucleic acid binding
protein binding
calmodulin binding
1-phosphatidylinositol binding
zinc ion binding

Cellular Component

cytoplasm
early endosome
cytosol
serine-pyruvate aminotransferase complex
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000322349
Coding exons: 29
Length: 158695
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125744
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.38	536	634	0.846	0.0000305	9283
Missense (PolyPhen)		140	195.62	0.71566		2858
Synonymous	-0.0560	238	237	1.00	0.0000118	2418
Loss of Function	6.90	18	87.8	0.205	0.00000423	1145

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00042	0.00040	rare
East Asian	0.00022	0.00016	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00022	0.00021	rare
South Asian	0.00011	0.000098	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in endosomal trafficking.;

Recessive Scores

pRec: 0.355

Intolerance Scores

LoFtool: 0.677
RVIS EVS: -0.55
RVIS percentile EVS: 20

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.334

Gene Damage Prediction

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