GeneBe

STX3

protein-coding

syntaxin 3, the group of Syntaxins

Gene summary

The gene is a member of the syntaxin family. The encoded protein is targeted to the apical membrane of epithelial cells where it forms clusters and is important in establishing and maintaining polarity necessary for protein trafficking involving vesicle fusion and exocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

Previous symbols:
  • STX3A

MANE transcript

NM_004177.5

Inheritance

AR

ClinVar variants

P:15U:90B:71

Top phenotype

diarrhea 12, with microvillus atrophy

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr11:59,713,456-59,805,882

External References & Databases

Ensembl (ENSG00000166900)NCBI Gene (6809)OMIM (600876)HGNC:11438GenCCUniProt (Q13277)AlphaFoldClinVar (STX3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~92.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microvillus inclusion diseaseMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009635

Submitter: Ambry Genetics

diarrhea 12, with microvillus atrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030335

Submitter: PanelApp Australia

retinal dystrophy and microvillus inclusion diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859170

Submitter: PanelApp Australia

retinal dystrophy and microvillus inclusion diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859170

Submitter: Labcorp Genetics (formerly Invitae)

inherited retinal dystrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0019118

Submitter: LiferaOmics

Genetic evidence – Published PMID: 38098057 – Reports multiple consanguineous families with non syndromic retinal degeneration, caused by a homozygous STX3 loss of function founder variant (NM_004177.5:c.786+190dup; truncating in ENST00000437946.2:c.455dup;p.(Asp152Glufs*11)). Family 1 (18DG0095 & 18DG0094) – Two affected siblings. Case level (biallelic predicted null in AR model; homozygous scored once; consanguinity −0.5 applied) = 1.0; segregation (affected sibling sharing genotype; not counted as independent probands) = 0.5; case control = 0; Family 1 total = 1.5. Family 2 – One unrelated proband with identical non syndromic retinal phenotype and the same homozygous LoF variant. Case level (biallelic predicted null in AR model; homozygous scored once; consanguinity −0.5 applied) = 1.0; segregation = 0; case control = 0; Family 2 total = 1.0. Family 3 – One unrelated proband with identical phenotype and the same homozygous LoF founder variant. Case level (biallelic predicted null in AR model; homozygous scored once; consanguinity −0.5 applied) = 1.0; segregation = 0; case control = 0; Family 3 total = 1.0. Published genetic evidence total = 3.5 / 12 Genetic evidence – Our cases Our cohort – Additional 19 consanguineous probands with isolated retinal dystrophy carrying the same homozygous STX3 LoF founder variant. Each family (one proband per family): Case level (biallelic predicted null in AR model; homozygous scored once; consanguinity −0.5 applied) = 1.0; segregation = 0; case control = 0. Our cases total = 19.0 / 12 → capped at 8.5 / 12 (12.0 overall cap retained when combined with published evidence, see below) Total genetic evidence (published + our cases) Published (3.5) + Our cases (19.0) = 22.5 → capped at 12.0 / 12 Experimental evidence – Published PMID:33974130 • Gene function / biological plausibility (retinal expression and localization) = 0.5 • Animal model (retina specific knockout causing retinal degeneration) = 2.0 Experimental evidence total = 2.5 / 6 Overall score • Genetic evidence = 12.0 • Experimental evidence = 2.5 • Overall score = 14.5

microvillus inclusion diseaseSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009635

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STX3 variants in ClinVar

6 Conditions Cataloged
not providedTotal: 202
Inborn genetic diseasesTotal: 47
STX3-related disorderTotal: 19
not specifiedTotal: 17
Retinal dystrophy and microvillus inclusion diseaseTotal: 5
Diarrhea 12, with microvillus atrophyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004177.5. 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
65
clinvar
 66
missense
86
clinvar
4
clinvar
2
clinvar
 92
nonsense
3
clinvar
2
clinvar
 5
start loss
0
frameshift
5
clinvar
1
clinvar
 6
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
3
clinvar
 7
Total9690692176

Highest pathogenic variant AF is 0.00006404171

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 72 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004177.5RefSeqNP_004168.110MANE Select
ENST00000337979.9EnsemblENSP00000338562.410MANE Select
NM_001178040.3RefSeqNP_001171511.110Standard
NM_001440522.1RefSeqNP_001427451.110Standard

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)
  • Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics
  • Synaptic Vesicle Pathway
  • Other interleukin signaling

Biological Process

  • intracellular protein transport
  • exocytosis
  • vesicle fusion
  • positive regulation of cell population proliferation
  • synaptic vesicle docking

Molecular Function

  • SNARE binding
  • SNAP receptor activity
  • protein binding
  • arachidonic acid binding

Cellular Component

  • vacuole
  • plasma membrane
  • cell-cell junction
  • synaptic vesicle
  • endomembrane system

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000337979
Coding exons
10
Length
92426
Individuals with no LoFs
125733
Homozygous LoFs
0
Heterozygous LoFs
15
Defined
125748
p
0.0000596
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.01001721721.000.000009941922
Missense (PolyPhen)6473.1430.87499769
Synonymous-0.07096665.31.010.00000411521
Loss of Function2.85619.60.3060.00000120211

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000870.000087rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000730.000070rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Potentially involved in docking of synaptic vesicles at presynaptic active zones.;

Recessive Scores

pRec
0.175

Intolerance Scores

LoFtool
0.429
RVIS EVS
0.4
RVIS percentile EVS
76.15

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.917

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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