STXBP2

syntaxin binding protein 2

Basic information

Region (hg38): 19:7636772-7647873

Links

ENSG00000076944

∙ NCBI:6813 ∙ OMIM:601717 ∙ HGNC:11445 ∙ Uniprot:Q15833 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

familial hemophagocytic lymphohistiocytosis 5 (Strong), mode of inheritance: AR
hereditary hemophagocytic lymphohistiocytosis (Supportive), mode of inheritance: AR
familial hemophagocytic lymphohistiocytosis 5 (Definitive), mode of inheritance: AR
microvillus inclusion disease (Limited), mode of inheritance: AR
familial hemophagocytic lymphohistiocytosis 5 (Definitive), mode of inheritance: AR
familial hemophagocytic lymphohistiocytosis 5 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemophagocytic lymphohistiocytosis, familial 5, with or without microvillous inclusion disease	AR	Allergy/Immunology/Infectious; Gastrointestinal	Antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response; The condition can involve hematologic manifestations as well as enteropathy, and awareness may allow medical (eg, with anti-interferon-gamma antibody and corticosteroids) and nutritional interventions related to the sequelae; Chemo/immunotherapy can achieve clinical stability prior to allogeneic hematopoietic cell transplantation (HCT), the only curative therapy.	Allergy/Immunology/Infectious; Gastrointestinal; Neurologic	19804848; 19884660; 20798128; 23382066; 29266534; 32374962

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STXBP2 gene.

Familial hemophagocytic lymphohistiocytosis 5 (32 variants)
Familial hemophagocytic lymphohistiocytosis (2 variants)
STXBP2-related disorder (1 variants)
not provided (1 variants)
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 5, WITHOUT MICROVILLUS INCLUSION DISEASE (1 variants)
Autoinflammatory syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STXBP2 gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.

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			6 clinvar	234 clinvar	2 clinvar	242
missense	2 clinvar	6 clinvar	306 clinvar	9 clinvar	1 clinvar	324
nonsense	11 clinvar	8 clinvar	2 clinvar			21
start loss						0
frameshift	17 clinvar	10 clinvar	1 clinvar			28
splice donor/acceptor (+/-2bp)	2 clinvar	27 clinvar	2 clinvar			31
Total	32	51	317	243	3

Highest pathogenic variant AF is 0.000210228

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STXBP2	protein_coding	protein_coding	ENST00000221283	19	10993

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.04e-8	0.982	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.481	344	370	0.930	0.0000256	3831
Missense in Polyphen		120	134.26	0.89378		1559
Synonymous	-1.15	180	161	1.11	0.0000122	1178
Loss of Function	2.24	17	30.3	0.561	0.00000132	385

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000339	0.000330
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.000162	0.000158
Middle Eastern	0.00	0.00
South Asian	0.000164	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in intracellular vesicle trafficking and vesicle fusion with membranes. Contributes to the granule exocytosis machinery through interaction with soluble N- ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins that regulate membrane fusion. Regulates cytotoxic granule exocytosis in natural killer (NK) cells. {ECO:0000269|PubMed:19804848, ECO:0000269|PubMed:19884660}.;
Pathway: Splicing factor NOVA regulated synaptic proteins;Insulin Signaling;Other interleukin signaling;Signaling by Interleukins;Cytokine Signaling in Immune system;Immune System;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Recessive Scores

pRec: 0.132

Intolerance Scores

loftool: 0.607
rvis_EVS: 0.43
rvis_percentile_EVS: 77.29

Haploinsufficiency Scores

pHI: 0.543
hipred: N
hipred_score: 0.473
ghis: 0.488

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Stxbp2
Phenotype: immune system phenotype; respiratory system phenotype; hematopoietic system 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); cellular phenotype;

Gene ontology

Biological process: leukocyte mediated cytotoxicity;platelet degranulation;vesicle docking involved in exocytosis;protein transport;regulation of mast cell degranulation;neutrophil degranulation;cellular response to interferon-gamma
Cellular component: extracellular region;cytosol;plasma membrane;apical plasma membrane;specific granule;azurophil granule;zymogen granule membrane;cytolytic granule;phagocytic vesicle;extracellular exosome;tertiary granule
Molecular function: protein binding;syntaxin-1 binding;syntaxin-3 binding