STX11

syntaxin 11, the group of Syntaxins

Basic information

Region (hg38): 6:144150486-144191939

Links

ENSG00000135604 ∙ NCBI:8676 ∙ OMIM:605014 ∙ HGNC:11429 ∙ Uniprot:O75558 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial hemophagocytic lymphohistiocytosis 4 (Strong), mode of inheritance: AR
• hereditary hemophagocytic lymphohistiocytosis (Supportive), mode of inheritance: AR
• familial hemophagocytic lymphohistiocytosis 4 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemophagocytic lymphohistiocytosis, familial, 4	AR	Allergy/Immunology/Infectious; Oncologic	Antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response. Chemo/immunotherapy can be beneficial; HSCT has been described	Allergy/Immunology/Infectious; Neurologic; Oncologic	15703195; 16278825; 16582076; 24459464; 32374962
Some individuals have been described as having remission without treatment; It has been suggested that variants may also confer risk for other malignancies.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STX11 gene.

• Familial hemophagocytic lymphohistiocytosis 4 (309 variants)
• Familial hemophagocytic lymphohistiocytosis (21 variants)
• not provided (12 variants)
• Autoinflammatory syndrome (11 variants)
• not specified (7 variants)
• Inborn genetic diseases (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STX11 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			3	71		74
missense	1		113	3	1	118
nonsense	4	5				9
start loss						0
frameshift	6	7				13
inframe indel			4			4
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			80	8	20	108
Total	11	12	200	82	21

Highest pathogenic variant AF is 0.0000264

Variants in STX11

This is a list of pathogenic ClinVar variants found in the STX11 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-144150569-C-T		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Jan 13, 2018)
6-144150584-C-G		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Mar 23, 2018)
6-144150622-C-T		Familial hemophagocytic lymphohistiocytosis 4	Benign (Apr 27, 2017)
6-144150638-C-T		Familial hemophagocytic lymphohistiocytosis	Uncertain significance (Jun 14, 2016)
6-144186623-G-A		Autoinflammatory syndrome	Uncertain significance (Aug 01, 2018)
6-144186636-C-A		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Sep 13, 2022)
6-144186638-G-A		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Aug 27, 2021)
6-144186638-G-T		Familial hemophagocytic lymphohistiocytosis 4 • Inborn genetic diseases	Uncertain significance (Sep 12, 2022)
6-144186640-C-T		Familial hemophagocytic lymphohistiocytosis 4	Likely benign (Jan 04, 2024)
6-144186642-A-G		Familial hemophagocytic lymphohistiocytosis 4	Likely benign (Aug 15, 2021)
6-144186644-C-T		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Aug 16, 2022)
6-144186647-A-C		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Aug 14, 2021)
6-144186648-ACTT-A		Familial hemophagocytic lymphohistiocytosis • Familial hemophagocytic lymphohistiocytosis 4 • Autoinflammatory syndrome	Uncertain significance (Sep 01, 2022)
6-144186653-T-C		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Aug 16, 2022)
6-144186653-T-G		Familial hemophagocytic lymphohistiocytosis 4 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 29, 2024)
6-144186660-G-A		Familial hemophagocytic lymphohistiocytosis 4	Likely benign (Dec 03, 2023)
6-144186661-T-G		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Jun 16, 2020)
6-144186663-C-T		Familial hemophagocytic lymphohistiocytosis 4	Likely benign (Jun 15, 2022)
6-144186673-G-A		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Mar 02, 2022)
6-144186678-G-A		Familial hemophagocytic lymphohistiocytosis 4	Likely benign (Jul 20, 2022)
6-144186680-A-G		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Nov 11, 2021)
6-144186684-C-T		Familial hemophagocytic lymphohistiocytosis 4	Likely benign (Aug 29, 2023)
6-144186685-C-T		Inborn genetic diseases	Uncertain significance (May 11, 2022)
6-144186690-C-T		Familial hemophagocytic lymphohistiocytosis 4	Conflicting classifications of pathogenicity (Oct 20, 2023)
6-144186691-G-C		Familial hemophagocytic lymphohistiocytosis 4	Uncertain significance (Sep 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STX11	protein_coding	protein_coding	ENST00000367568	1	37845

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000474	0.688	125723	0	21	125744	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.131	211	206	1.03	0.0000177	1884
Missense in Polyphen		71	78.502	0.90444		658
Synonymous	0.150	96	97.9	0.981	0.00000968	559
Loss of Function	0.806	6	8.54	0.702	4.64e-7	87

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000434	0.000434
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: SNARE that acts to regulate protein transport between late endosomes and the trans-Golgi network.
• Disease: DISEASE: Familial hemophagocytic lymphohistiocytosis 4 (FHL4) [MIM:603552]: A rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia. {ECO:0000269|PubMed:15703195}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: SNARE interactions in vesicular transport - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics (Consensus)

Recessive Scores

• pRec: 0.183

Intolerance Scores

• loftool: 0.438
• rvis_EVS: 0.64
• rvis_percentile_EVS: 83.98

Haploinsufficiency Scores

• pHI: 0.227
• hipred: Y
• hipred_score: 0.539
• ghis: 0.508

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stx11
• Phenotype: immune system phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: intracellular protein transport;exocytosis;vesicle fusion;synaptic vesicle fusion to presynaptic active zone membrane;vesicle docking;membrane fusion
• Cellular component: Golgi apparatus;plasma membrane;synaptic vesicle;endomembrane system;integral component of membrane;SNARE complex;presynaptic membrane;presynaptic active zone membrane
• Molecular function: SNARE binding;SNAP receptor activity;protein binding