STX1A

protein-coding

syntaxin 1A, the group of Syntaxins

Gene summary

This gene encodes a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins possess a single C-terminal transmembrane domain, a SNARE [Soluble NSF (N-ethylmaleimide-sensitive fusion protein)-Attachment protein REceptor] domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. This gene product is a key molecule in ion channel regulation and synaptic exocytosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

Previous symbols:

STX1

MANE transcript

NM_004603.4

Inheritance

AR, AD

ClinVar variants

P:4U:30B:12

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr7:73,699,206-73,719,672

External References & Databases

Ensembl (ENSG00000106089)

Transcript & Mutation Effects

hg38 • Region Span ~20.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: G2P

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: G2P

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

cystic fibrosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009061

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STX1A variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 29

not providedTotal: 9

Intellectual disabilityTotal: 7

STX1A-related disorderTotal: 4

SeizureTotal: 4

AutismTotal: 3

Neurodevelopmental abnormalityTotal: 1

STX1A-associated neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004603.4. 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			1 clinvar	11 clinvar		12
missense		3 clinvar	27 clinvar	1 clinvar		31
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	1	3	30	12	0	46

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004603.4	RefSeq	NP_004594.1	10	MANE Select
ENST00000222812.8	Ensembl	ENSP00000222812.3	10	MANE Select
NM_001165903.2	RefSeq	NP_001159375.1	10	Standard
ENST00000395154.7	Ensembl	ENSP00000378583.3	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Synaptic vesicle cycle - Homo sapiens (human)
SNARE interactions in vesicular transport - Homo sapiens (human)
Amphetamine addiction - Homo sapiens (human)
Insulin secretion - Homo sapiens (human)
Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics

Biological Process

positive regulation of neurotransmitter secretion
intracellular protein transport
exocytosis
vesicle fusion
response to gravity

Molecular Function

SNARE binding
SNAP receptor activity
protein binding
calcium channel inhibitor activity
chloride channel inhibitor activity

Cellular Component

extracellular region
cytosol
plasma membrane
synaptic vesicle
voltage-gated potassium channel complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000222812
Coding exons: 10
Length: 20467
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125722
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.40	98	191	0.512	0.0000123	1930
Missense (PolyPhen)		23	67.253	0.34199		621
Synonymous	0.950	66	76.6	0.862	0.00000555	507
Loss of Function	3.50	1	16.2	0.0618	8.35e-7	194

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in hormone and neurotransmitter exocytosis (By similarity). Potentially involved in docking of synaptic vesicles at presynaptic active zones. May mediate Ca(2+)- regulation of exocytosis acrosomal reaction in sperm. {ECO:0000250|UniProtKB:P32851}.;
Disease: DISEASE: Note=STX1A is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. {ECO:0000305|PubMed:9311751}.;

Recessive Scores

pRec: 0.438

Intolerance Scores

LoFtool: 0.298
RVIS EVS: -0.36
RVIS percentile EVS: 28.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.722

Gene Damage Prediction

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