ESYT3

protein-coding

extended synaptotagmin 3, the group of Extended synaptotagmins

Gene summary

Predicted to enable calcium ion binding activity; phosphatidylinositol binding activity; and phospholipid binding activity. Predicted to be involved in endoplasmic reticulum-plasma membrane tethering and lipid transport. Located in cytoplasmic side of plasma membrane; endoplasmic reticulum membrane; and endoplasmic reticulum-plasma membrane contact site. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

FAM62C

MANE transcript

NM_031913.5

Inheritance

—

ClinVar variants

U:139B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr3:138,434,586-138,481,686

External References & Databases

Ensembl (ENSG00000158220)

Transcript & Mutation Effects

hg38 • Region Span ~47.1 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 ESYT3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 130

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031913.5. 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			2 clinvar			2
missense			129 clinvar	6 clinvar		135
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	139	6	0	145

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031913.5	RefSeq	NP_114119.2	23	MANE Select
ENST00000389567.9	Ensembl	ENSP00000374218.4	23	MANE Select
NM_001322831.2	RefSeq	NP_001309760.1	23	Standard
NM_001322834.2	RefSeq	NP_001309763.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Metabolism
Glycosphingolipid metabolism
Sphingolipid metabolism

Biological Process

lipid transport
endoplasmic reticulum-plasma membrane tethering

Molecular Function

calcium ion binding
protein binding
calcium-dependent phospholipid binding
phosphatidylethanolamine binding
phosphatidylcholine binding

Cellular Component

endoplasmic reticulum membrane
integral component of plasma membrane
intrinsic component of endoplasmic reticulum membrane
extrinsic component of cytoplasmic side of plasma membrane
organelle membrane contact site

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389567
Coding exons: 23
Length: 47101
Individuals with no LoFs: 125494
Homozygous LoFs: 0
Heterozygous LoFs: 254
Defined: 125748
p: 0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0700	490	494	0.991	0.0000273	5707
Missense (PolyPhen)		161	184.16	0.87425		2179
Synonymous	0.922	187	204	0.918	0.0000109	1818
Loss of Function	0.927	42	49.0	0.857	0.00000269	537

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0010	notable
Latino/Admixed American	0.0018	0.0017	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0030	0.0029	notable
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00068	0.00067	rare
South Asian	0.0012	0.0011	notable
Other	0.0017	0.0016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport (By similarity). Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. {ECO:0000250, ECO:0000269|PubMed:23791178}.;

Intolerance Scores

LoFtool: 0.561
RVIS EVS: 1.9
RVIS percentile EVS: 97.34

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.139

Gene Damage Prediction

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