SYT4

protein-coding

synaptotagmin 4, the group of Synaptotagmins

Gene summary

Predicted to enable several functions, including calcium ion sensor activity; calcium-dependent phospholipid binding activity; and protein dimerization activity. Involved in negative regulation of catecholamine secretion and positive regulation of dendrite extension. Predicted to be located in neuron projection terminus and secretory vesicle. Predicted to be active in several cellular components, including axon; exocytic vesicle; and synapse. Biomarker of type 2 diabetes mellitus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_020783.4

Inheritance

—

ClinVar variants

U:42B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr18:43,267,892-43,277,535

External References & Databases

Ensembl (ENSG00000132872)

Transcript & Mutation Effects

hg38 • Region Span ~9.6 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 SYT4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020783.4. 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						0
missense			40 clinvar	3 clinvar		43
nonsense						0
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	42	3	0	45

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020783.4	RefSeq	NP_065834.1	4	MANE Select
ENST00000255224.8	Ensembl	ENSP00000255224.2	4	MANE Select
ENST00000590752.5	Ensembl	ENSP00000466930.1	4	Standard
ENST00000590752.6	Ensembl	ENSP00000466930.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

brain development
memory
positive regulation of glutamate secretion
regulation of dopamine secretion
vesicle-mediated transport

Molecular Function

SNARE binding
phosphatidylserine binding
calcium ion binding
protein binding
calcium-dependent phospholipid binding

Cellular Component

plasma membrane
cell junction
integral component of Golgi membrane
integral component of synaptic vesicle membrane
axon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000255224
Coding exons: 4
Length: 9773
Individuals with no LoFs: 125688
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125706
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0635	213	216	0.988	0.0000102	2779
Missense (PolyPhen)		74	86.452	0.85596		1161
Synonymous	-1.17	100	86.2	1.16	0.00000431	831
Loss of Function	2.74	3	14.1	0.212	7.19e-7	211

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000062	0.000058	rare
Ashkenazi Jewish	0.00069	0.00069	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:P50232, ECO:0000269|PubMed:23999003}.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.609
RVIS EVS: 0.02
RVIS percentile EVS: 55.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.945

Gene Damage Prediction

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