SYT6

protein-coding

synaptotagmin 6, the group of Synaptotagmins

Gene summary

The protein encoded by this gene belongs to the synaptotagmin family. Synaptotagmins share a common domain structure that includes a transmembrane domain and a cytoplasmic region composed of 2 C2 domains, and are involved in calcium-dependent exocytosis of synaptic vesicles. This protein has been shown to be a key component of the secretory machinery involved in acrosomal exocytosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2011]

MANE transcript

NM_001253772.2

Inheritance

—

ClinVar variants

U:60

Top phenotype

Breast ductal adenocarcinoma

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr1:114,089,291-114,153,880

External References & Databases

Ensembl (ENSG00000134207)

Transcript & Mutation Effects

hg38 • Region Span ~64.6 kb

Loading mutation effect viewer...

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 SYT6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 55

Breast ductal adenocarcinomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001253772.2. 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			58 clinvar			58
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	60	0	0	60

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001253772.2	RefSeq	NP_001240701.1	7	MANE Select
ENST00000610222.3	Ensembl	ENSP00000476396.1	7	MANE Select
NM_001270805.2	RefSeq	NP_001257734.1	6	Standard
NM_001366223.1	RefSeq	NP_001353152.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of dopamine secretion
vesicle-mediated transport
calcium ion regulated exocytosis
regulation of calcium ion-dependent exocytosis
acrosomal vesicle exocytosis

Molecular Function

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

Cellular Component

cytosol
plasma membrane
integral component of membrane
extrinsic component of membrane
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000609117
Coding exons: 6
Length: 64629
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125748
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.168	254	262	0.971	0.0000159	2810
Missense (PolyPhen)		108	132.06	0.81782		1415
Synonymous	0.108	101	102	0.986	0.00000604	831
Loss of Function	2.19	6	15.2	0.395	7.05e-7	193

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0	0.0	absent
Other	0.00050	0.00049	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. May mediate Ca(2+)- regulation of exocytosis in acrosomal reaction in sperm (By similarity). {ECO:0000250|UniProtKB:Q9R0N8}.;

Recessive Scores

pRec: 0.132

Intolerance Scores

LoFtool: 0.463
RVIS EVS: -0.89
RVIS percentile EVS: 10.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.178

Gene Damage Prediction

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