STX4

syntaxin 4, the group of Syntaxins

Basic information

Region (hg38): 16:31032889-31042975

Previous symbols: [ "STX4A" ]

Links

ENSG00000103496

∙ NCBI:6810 ∙ OMIM:186591 ∙ HGNC:11439 ∙ Uniprot:Q12846 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 123	AR	Audiologic/Otolaryngologic	As some presentations may involve prelingual hearing loss, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	36355422

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STX4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STX4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			5 clinvar	2 clinvar		7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	5	2	0

Variants in STX4

This is a list of pathogenic ClinVar variants found in the STX4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
16-31034056-T-C	not specified	Uncertain significance (Dec 08, 2023)	3171762
16-31034089-G-T	not specified	Uncertain significance (May 03, 2023)	2542118
16-31034266-A-G	not specified	Uncertain significance (Jun 03, 2024)	3323473
16-31034272-A-G	not specified	Likely benign (Mar 16, 2022)	2382481
16-31034331-T-C	Sensorineural hearing loss disorder • Hearing loss, autosomal recessive 123	Pathogenic/Likely pathogenic (Mar 04, 2024)	1676769
16-31034518-A-G	not specified	Uncertain significance (Jun 24, 2022)	2205957
16-31035014-G-A	not specified	Likely benign (Aug 13, 2021)	2220377
16-31037950-G-A	not specified	Uncertain significance (Aug 02, 2021)	2359922
16-31038609-G-A	not specified	Uncertain significance (Oct 07, 2024)	3450979
16-31038642-A-C	not specified	Uncertain significance (Nov 08, 2021)	2226122
16-31039549-G-A	not specified	Uncertain significance (Aug 07, 2024)	3450978
16-31039556-C-T		Uncertain significance (Feb 21, 2024)	3024141
16-31039578-G-A	not specified	Uncertain significance (May 03, 2024)	3323472

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STX4	protein_coding	protein_coding	ENST00000313843	10	10087

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.30e-7	0.599	125703	0	45	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.11	135	176	0.765	0.0000107	1947
Missense in Polyphen		38	57.412	0.66189		632
Synonymous	0.159	72	73.7	0.976	0.00000473	556
Loss of Function	1.06	13	17.9	0.728	8.25e-7	211

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000245	0.000181
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000168	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000301	0.000299
Middle Eastern	0.000168	0.000163
South Asian	0.0000660	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Plasma membrane t-SNARE that mediates docking of transport vesicles. Necessary for the translocation of SLC2A4 from intracellular vesicles to the plasma membrane. Together with STXB3 and VAMP2, may also play a role in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes (By similarity). May also play a role in docking of synaptic vesicles at presynaptic active zones. {ECO:0000250}.;
Pathway: Vasopressin-regulated water reabsorption - Homo sapiens (human);SNARE interactions in vesicular transport - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Insulin Signaling;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Other interleukin signaling;Signaling by Interleukins;Vesicle-mediated transport;Membrane Trafficking;Cytokine Signaling in Immune system;Immune System;Adaptive Immune System;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;Disinhibition of SNARE formation;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;EGFR1;Hemostasis;ER-Phagosome pathway;Stabilization and expansion of the E-cadherin adherens junction;Insulin-mediated glucose transport (Consensus)

Intolerance Scores

loftool: 0.705
rvis_EVS: -0.58
rvis_percentile_EVS: 18.44

Haploinsufficiency Scores

pHI: 0.0983
hipred: Y
hipred_score: 0.550
ghis: 0.584

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.936

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Stx4a
Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Gene ontology

Biological process: intracellular protein transport;exocytosis;vesicle fusion;positive regulation of cell population proliferation;regulation of exocytosis;cytokine-mediated signaling pathway;positive regulation of cell migration;synaptic vesicle fusion to presynaptic active zone membrane;response to hydroperoxide;SNARE complex assembly;positive regulation of insulin secretion involved in cellular response to glucose stimulus;positive regulation of catalytic activity;positive regulation of eosinophil degranulation;positive regulation of cell adhesion;vesicle docking;organelle fusion;positive regulation of chemotaxis;positive regulation of immunoglobulin secretion;long-term synaptic potentiation;cellular response to interferon-gamma;regulation of extrinsic apoptotic signaling pathway via death domain receptors;positive regulation of protein localization to plasma membrane;vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane;positive regulation of protein localization to cell surface
Cellular component: storage vacuole;extracellular space;endosome;vacuole;trans-Golgi network;cytosol;plasma membrane;synaptic vesicle;cell surface;endomembrane system;membrane;integral component of membrane;basolateral plasma membrane;lamellipodium;phagocytic vesicle membrane;SNARE complex;myelin sheath adaxonal region;somatodendritic compartment;specific granule;presynaptic membrane;dendritic spine;lateral loop;synapse;perinuclear region of cytoplasm;presynaptic active zone membrane;extracellular exosome;postsynapse;glutamatergic synapse
Molecular function: SNARE binding;SNAP receptor activity;protein binding;sphingomyelin phosphodiesterase activator activity