SYT7

protein-coding

synaptotagmin 7, the group of Synaptotagmins

Gene summary

This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate calcium-dependent regulation of membrane trafficking in synaptic transmission. A similar protein in rodents mediates hormone secretion and lysosome exocytosis. In humans, expression of this gene has been associated with prostate cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

Previous symbols:
  • PCANAP7

MANE transcript

NM_001365809.2

Inheritance

—

ClinVar variants

U:44B:3

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr11:61,513,714-61,581,148

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~67.4 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 SYT7 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 40
not providedTotal: 3
Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001365809.2. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
2
missense
40
clinvar
1
clinvar
1
clinvar
42
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
3
clinvar
3
Total00442147
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001365809.2RefSeqNP_001352738.113MANE Select
ENST00000539008.6EnsemblENSP00000439694.113MANE Select
NM_001252065.2RefSeqNP_001238994.110Standard
NM_001300773.2RefSeqNP_001287702.110Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
syt7bDanio rerio

Structure: motor neuron

Quality: physical object quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Neuronal System
  • Neurexins and neuroligins
  • Protein-protein interactions at synapses

Biological Process

  • plasma membrane repair
  • phagocytosis
  • regulation of dopamine secretion
  • vesicle-mediated transport
  • calcium ion regulated exocytosis

Molecular Function

  • SNARE binding
  • phosphatidylserine binding
  • calcium ion binding
  • protein binding
  • calmodulin binding

Cellular Component

  • lysosome
  • lysosomal membrane
  • peroxisome
  • peroxisomal membrane
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000540677
Coding exons
10
Length
65836
Individuals with no LoFs
125090
Homozygous LoFs
0
Heterozygous LoFs
2
Defined
125092
p
0.00000799
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.211892960.6380.00002033094
Missense (PolyPhen)2876.9810.36373827
Synonymous0.1741301330.9810.0000103955
Loss of Function3.63219.10.1059.86e-7245

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.000100.000099rare
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.00000890.0000089rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory and synaptic vesicles through Ca(2+) and phospholipid binding to the C2 domain (By similarity). Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis (By similarity). SYT7 binds Ca(2+) with high affinity and slow kinetics compared to other synaptotagmins (By similarity). Involved in Ca(2+)-triggered lysosomal exocytosis, a major component of the plasma membrane repair (PubMed:11342594). Ca(2+)- regulated delivery of lysosomal membranes to the cell surface is also involved in the phagocytic uptake of particles by macrophages (By similarity). Ca(2+)-triggered lysosomal exocytosis also plays a role in bone remodeling by regulating secretory pathways in osteoclasts and osteoblasts (By similarity). In case of infection, involved in participates cell invasion by Trypanosoma cruzi via Ca(2+)-triggered lysosomal exocytosis (PubMed:11342594, PubMed:15811535). Involved in cholesterol transport from lysosome to peroxisome by promoting membrane contacts between lysosomes and peroxisomes: probably acts by promoting vesicle fusion by binding phosphatidylinositol-4,5-bisphosphate on peroxisomal membranes (By similarity). Acts as a key mediator of synaptic facilitation, a process also named short-term synaptic potentiation: synaptic facilitation takes place at synapses with a low initial release probability and is caused by influx of Ca(2+) into the axon terminal after spike generation, increasing the release probability of neurotransmitters (By similarity). Probably mediates synaptic facilitation by directly increasing the probability of release (By similarity). May also contribute to synaptic facilitation by regulating synaptic vesicle replenishment, a process required to ensure that synaptic vesicles are ready for the arrival of the next action potential: SYT7 is required for synaptic vesicle replenishment by acting as a sensor for Ca(2+) and by forming a complex with calmodulin (By similarity). Also acts as a regulator of Ca(2+)-dependent insulin and glucagon secretion in beta-cells (By similarity). Triggers exocytosis by promoting fusion pore opening and fusion pore expansion in chromaffin cells (By similarity). Also regulates the secretion of some non-synaptic secretory granules of specialized cells (By similarity). {ECO:0000250|UniProtKB:Q62747, ECO:0000250|UniProtKB:Q9R0N7, ECO:0000269|PubMed:11342594, ECO:0000269|PubMed:15811535}.;

Recessive Scores

pRec
0.131

Intolerance Scores

LoFtool
0.139
RVIS EVS
-0.67
RVIS percentile EVS
15.62

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.757

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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