SYTL2

protein-coding

synaptotagmin like 2, the group of Synaptotagmin like tandem C2 proteins|Protein phosphatase 1 regulatory subunits

Gene summary

The protein encoded by this gene is a synaptotagmin-like protein (SLP) that belongs to a C2 domain-containing protein family. The SLP homology domain (SHD) of this protein has been shown to specifically bind the GTP-bound form of Ras-related protein Rab-27A (RAB27A). This protein plays a role in RAB27A-dependent vesicle trafficking and controls melanosome distribution in the cell periphery. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jun 2009]

MANE transcript

NM_206927.4

Inheritance

—

ClinVar variants

U:265B:29

Top phenotype

Angioedema

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr11:85,694,224-85,811,159

External References & Databases

Ensembl (ENSG00000137501)

Transcript & Mutation Effects

hg38 • Region Span ~116.9 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 SYTL2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 272

not providedTotal: 14

AngioedemaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_206927.4. 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			4 clinvar	4 clinvar	1 clinvar	9
missense			258 clinvar	21 clinvar	3 clinvar	282
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	265	25	4	294

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 126 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_206927.4	RefSeq	NP_996810.2	19	MANE Select
ENST00000359152.10	Ensembl	ENSP00000352065.7	19	MANE Select
NM_001162951.4	RefSeq	NP_001156423.1	18	Standard
NM_001162952.3	RefSeq	NP_001156424.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Deregulation of Rab and Rab Effector Genes in Bladder Cancer

Biological Process

intracellular protein transport
exocytosis
vesicle docking involved in exocytosis
negative regulation of phosphatase activity
vesicle-mediated transport

Molecular Function

phosphatidylserine binding
protein binding
phosphatidylinositol-4,5-bisphosphate binding
Rab GTPase binding
phosphatase binding

Cellular Component

cytoplasm
plasma membrane
membrane
extrinsic component of plasma membrane
melanosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354566
Coding exons: 13
Length: 116918
Individuals with no LoFs: 125667
Homozygous LoFs: 2
Heterozygous LoFs: 78
Defined: 125747
p: 0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.20	725	639	1.13	0.0000305	8354
Missense (PolyPhen)		192	172.33	1.1142		2277
Synonymous	0.839	216	232	0.930	0.0000115	2421
Loss of Function	1.49	38	49.3	0.771	0.00000227	683

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0011	0.0010	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.00075	0.00075	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform 1 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. It is required for cytotoxic granule docking at the immunologic synapse. Isoform 4 binds phosphatidylserine (PS) and phosphatidylinositol- 4,5-bisphosphate (PIP2) and promotes the recruitment of glucagon- containing granules to the cell membrane in pancreatic alpha cells. Binding to PS is inhibited by Ca(2+) while binding to PIP2 is Ca(2+) insensitive. {ECO:0000269|PubMed:17182843, ECO:0000269|PubMed:18266782, ECO:0000269|PubMed:18812475}.;

Recessive Scores

pRec: 0.0897

Intolerance Scores

LoFtool: 0.995
RVIS EVS: 1.34
RVIS percentile EVS: 94.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.111

Gene Damage Prediction

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