STXBP5L

protein-coding

syntaxin binding protein 5L, the group of WD repeat domain containing|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene is similar to syntaxin-binding protein 5 and contains ten N-terminal WD40 repeats, four variable region WD40 repeats, and a C-terminal R-SNARE domain. Studies of the orthologous proteins in mouse and rat have shown that the encoded protein may inhibit exocytosis in neurosecretory cells, and may negatively regulate the secretion of insulin. A missense variant in this gene is likely the cause of an infantile-onset neurodegenerative disorder diagnosed in two siblings of consanguineous parents. [provided by RefSeq, Jan 2017]

MANE transcript

NM_001308330.2

Inheritance

—

ClinVar variants

U:156B:10

Top phenotype

STXBP5L-related disorder

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr3:120,908,072-121,424,761

External References & Databases

Ensembl (ENSG00000145087)

Transcript & Mutation Effects

hg38 • Region Span ~516.7 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 STXBP5L variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 144

STXBP5L-related disorderTotal: 14

not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001308330.2. 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			1 clinvar	5 clinvar		6
missense			150 clinvar	5 clinvar		155
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	156	10	0	166

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001308330.2	RefSeq	NP_001295259.1	26	MANE Select
ENST00000471454.6	Ensembl	ENSP00000420019.1	26	MANE Select
NM_001348343.2	RefSeq	NP_001335272.1	27	Standard
NM_001348344.2	RefSeq	NP_001335273.1	26	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

exocytosis
protein transport
regulation of exocytosis
glucose homeostasis
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
Rab GTPase binding
syntaxin binding

Cellular Component

cytoplasm
plasma membrane
integral component of membrane
SNARE complex
neuromuscular junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000273666
Coding exons: 27
Length: 516690
Individuals with no LoFs: 124770
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 124794
p: 0.0000962

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.71	511	632	0.809	0.0000324	7752
Missense (PolyPhen)		180	251.99	0.71431		3127
Synonymous	-0.228	217	213	1.02	0.0000107	2257
Loss of Function	6.32	10	64.9	0.154	0.00000355	789

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00033	0.00032	rare
Latino/Admixed American	0.00013	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000072	0.000071	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in vesicle trafficking and exocytosis. {ECO:0000305}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.445
RVIS EVS: -0.44
RVIS percentile EVS: 24.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.541

Gene Damage Prediction

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