GeneBe

STXBP3

protein-coding

syntaxin binding protein 3

Gene summary

Involved in negative regulation of calcium ion-dependent exocytosis; neutrophil degranulation; and platelet aggregation. Located in cytosol; plasma membrane; and secretory granule. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_007269.4

Inheritance

AR

ClinVar variants

P:3U:74B:8

Top phenotype

inborn error of immunity

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr1:108,746,674-108,809,523

External References & Databases

Ensembl (ENSG00000116266)NCBI Gene (6814)OMIM (608339)HGNC:11446GenCCUniProt (O00186)AlphaFoldClinVar (STXBP3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~62.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inborn error of immunitySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0003778

Submitter: PanelApp Australia

arthrogryposis syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0015225

Submitter: LiferaOmics

Genetic evidence – Published PMID: 31130284 – Family 1 – one proband. Case-level (non-LOF start = 0.1; homozygous missense p.Ala208Thr; no consanguinity information → no deduction applied) = 0.1; Segregation = 0; Case-control = 0 Family 1 total = 0.1 PMID: 39504961 – Family 2 – one proband. Case-level (non-LOF start = 0.1; homozygous missense p.Ala208Thr; consanguinity not stated → no deduction applied) = 0.1; Segregation = 0; Case-control = 0 Family 2 total = 0.1 PMID: 39504961 – Family 3 – one proband. Case-level (non-LOF start = 0.1; homozygous missense p.Ala208Thr; consanguinity not stated → no deduction applied) = 0.1; Segregation = 0; Case-control = 0 Family 3 total = 0.1 Published genetic evidence total = 0.3 / 12 Genetic evidence – Our cases Family 1 – Two affected siblings. Case-level (non-LOF; homozygous; consanguinity) = 0.1; Segregation (affected sibling; genotype-confirmed; conservative assignment) = 0.1; Case-control = 0 Family 1 total = 0.1 Family 2 – One proband. Case-level (non-LOF; homozygous; no consanguinity deduction applied) = 0.1; Segregation = 0; Case-control = 0 Family 2 total = 0.1 Family 3 – One proband. Case-level (non-LOF start = 0.1; homozygous; no consanguinity deduction applied) = 0.1; Segregation = 0; Case-control = 0 Family 3 total = 0.1 Family 4 – Two affected siblings. Case-level (non-LOF; homozygous; no consanguinity deduction applied) = 0.1; Segregation (affected sibling; genotype-confirmed; conservative assignment) = 0.5; Case-control = 0 Family 4 total = 0.6 Our genetic evidence total = 0.9 / 12 Total genetic evidence (published AR + our cases) 0.3 (published AR) + 0.9 (our cases) = 1.2 / 12 Experimental evidence – Published No experimental evidence found at this time. Experimental evidence total = 0 / 6 Overall score Genetic evidence = 7.5 Experimental evidence = 0 Overall score = 1.2 / 18

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STXBP3 variants in ClinVar

5 Conditions Cataloged
not specifiedTotal: 71
not providedTotal: 4
Immune dysregulation, autoimmunity, and autoinflammationTotal: 2
STXBP3-related disordersTotal: 1
See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007269.4. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
6
clinvar
 9
missense
1
clinvar
67
clinvar
2
clinvar
 70
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
4
clinvar
 6
Total03748085
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_007269.4RefSeqNP_009200.219MANE Select
ENST00000370008.4EnsemblENSP00000359025.319MANE Select
ENST00000889910.1EnsemblENSP00000559969.118Standard
ENST00000889910.2EnsemblENSP00000559969.118Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
stxbp3Danio rerio

Structure: otolith

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Insulin Signaling
  • Disinhibition of SNARE formation
  • Response to elevated platelet cytosolic Ca2+
  • Platelet activation, signaling and aggregation
  • Hemostasis

Biological Process

  • cellular glucose homeostasis
  • vesicle docking involved in exocytosis
  • brain development
  • protein to membrane docking
  • insulin secretion

Molecular Function

  • protein binding
  • syntaxin-1 binding
  • syntaxin binding

Cellular Component

  • cytosol
  • plasma membrane
  • basolateral plasma membrane
  • apical plasma membrane
  • platelet alpha granule

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000370008
Coding exons
19
Length
62853
Individuals with no LoFs
125719
Homozygous LoFs
0
Heterozygous LoFs
23
Defined
125742
p
0.0000915
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.762163020.7140.00001493908
Missense (PolyPhen)61116.650.522911482
Synonymous1.18861010.8510.000004961037
Loss of Function3.491436.90.3800.00000196469

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.0000610.000058rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.0000540.000054rare
Finnish0.0000920.000092rare
European (Non-Finnish)0.0000890.000088rare
South Asian0.000100.000098rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Together with STX4 and VAMP2, may play a role in insulin-dependent movement of GLUT4 and in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes. {ECO:0000250}.;

Recessive Scores

pRec
0.146

Intolerance Scores

LoFtool
0.606
RVIS EVS
-0.51
RVIS percentile EVS
21.41

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.810

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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