STXBP2

syntaxin binding protein 2

Basic information

Region (hg38): 19:7636771-7647873

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

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 (819 variants)
• not specified (70 variants)
• not provided (69 variants)
• Autoinflammatory syndrome (36 variants)
• Inborn genetic diseases (24 variants)
• Familial hemophagocytic lymphohistiocytosis (15 variants)
• STXBP2-related condition (7 variants)
• Thrombocytopenia;Abnormal bleeding (2 variants)
• Abnormal bleeding;Thrombocytopenia (1 variants)
• HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 5, WITHOUT MICROVILLUS INCLUSION DISEASE (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.

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			7	165	3	175
missense	3	4	289	7	1	304
nonsense	9	6	2			17
start loss						0
frameshift	11	8	1			20
inframe indel	1		6			7
splice donor/acceptor (+/-2bp)	2	17	2		1	22
splice region	1	1	33	43	2	80
non coding			13	151	40	204
Total	26	35	320	323	45

Highest pathogenic variant AF is 0.000210

Variants in STXBP2

This is a list of pathogenic ClinVar variants found in the STXBP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-7636780-C-A			Benign (Nov 12, 2018)
19-7636862-T-C			Benign (Nov 12, 2018)
19-7637109-TG-T		not specified	Likely benign (-)
19-7637154-C-T		Familial hemophagocytic lymphohistiocytosis 5	Uncertain significance (Jul 11, 2022)
19-7637155-G-A		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Jan 15, 2024)
19-7637155-G-T		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Jul 06, 2023)
19-7637156-C-T		Familial hemophagocytic lymphohistiocytosis 5	Uncertain significance (Jun 13, 2022)
19-7637158-C-G			Uncertain significance (Feb 01, 2022)
19-7637161-G-C		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Oct 17, 2022)
19-7637163-G-A		Familial hemophagocytic lymphohistiocytosis 5	Uncertain significance (Jan 12, 2018)
19-7637165-C-T		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Jan 11, 2024)
19-7637170-G-A		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Aug 09, 2022)
19-7637171-G-A		Familial hemophagocytic lymphohistiocytosis 5	Uncertain significance (Jul 19, 2022)
19-7637173-G-C		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Jan 08, 2021)
19-7637173-G-T		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Aug 08, 2023)
19-7637176-G-A		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Jun 20, 2022)
19-7637176-G-C		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Dec 10, 2023)
19-7637178-T-C		Familial hemophagocytic lymphohistiocytosis 5	Uncertain significance (Jun 19, 2021)
19-7637178-T-TG		Familial hemophagocytic lymphohistiocytosis 5	Pathogenic (Oct 28, 2023)
19-7637179-G-A		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Feb 03, 2022)
19-7637179-G-C		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Oct 26, 2023)
19-7637179-G-T		Familial hemophagocytic lymphohistiocytosis 5	Likely benign (Aug 16, 2023)
19-7637185-A-G		Familial hemophagocytic lymphohistiocytosis 5 • STXBP2-related disorder	Uncertain significance (Jul 24, 2023)
19-7637191-G-A		Familial hemophagocytic lymphohistiocytosis 5	Likely pathogenic (Aug 31, 2023)
19-7637193-G-T		Familial hemophagocytic lymphohistiocytosis 5	Conflicting classifications of pathogenicity (Jan 25, 2024)

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