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Primary immunodeficiency

Gene: STXBP3

Amber List (moderate evidence)

STXBP3 (syntaxin binding protein 3)
EnsemblGeneIds (GRCh38): ENSG00000116266
EnsemblGeneIds (GRCh37): ENSG00000116266
OMIM: 608339, Gene2Phenotype
STXBP3 is in 2 panels

4 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: Sufficient number of cases presenting a relevant phenotype with some functional data. However, given that several families carried potentially contributory variants in other genes, going to maintain an Amber rating at this time in anticipation of further cases/clinical evidence to validate the pathogenicity of this gene.
Created: 9 Jun 2021, 11:31 a.m. | Last Modified: 9 Jun 2021, 11:31 a.m.
Panel Version: 2.425
Ouahed et al. 2021 (PMID: 33891011) report 5 unrelated families with 10 patients who presented with a similar phenotype including medically refractory infantile-onset IBD (10/10), severe bilateral sensorineural hearing loss (8/10), and, in the majority, recurrent infections (6/10). Heterozygous variants in STXBP3 were identified in 3 families (2 de novo, 1 paternally transmitted); while 5 sibs from 2 unrelated families harboured different compound het variants. Variants interfered with either intron splicing or protein stability and all were shown to reduce STXBP3 protein expression. Knock-down of STXBP3 in CaCo2 cells resulted in defects in cell polarity.

Additional variants not thought to be independently deleterious by the authors, but in pathways of interest or in known VEOIBD genes, were identified in 4/5 families.

* Note the previous review submitted by Kelsey Jones (GOSH) references an abstract briefly reporting on 4 of the families from PMID:33891011
Created: 9 Jun 2021, 11:23 a.m. | Last Modified: 9 Jun 2021, 11:23 a.m.
Panel Version: 2.424

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

10 individuals from 5 families reported.
Created: 10 May 2021, 10:31 a.m. | Last Modified: 10 May 2021, 10:31 a.m.
Panel Version: 2.421

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Very Early Onset Inflammatory Bowel Disease; Bilateral Sensorineural Hearing Loss; Immune Dysregulation

Publications

Variants in this GENE are reported as part of current diagnostic practice

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by Kelsey Jones (Great Ormond Street Hospital). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. Based on the available evidence this gene has been given an Amber rating.
Created: 1 Feb 2021, 1:56 p.m. | Last Modified: 1 Feb 2021, 1:56 p.m.
Panel Version: 2.401

Kelsey Jones (Great Ormond Street Hospital)

I don't know

Described as a monogenic cause of VEOIBD (recognised criteria for the R15 panel) in a report published in abstract form (DOI: https://doi.org/10.1053/j.gastro.2017.11.120). 8 patients from 4 unrelated families with defects in STXBP3 reportedly associated with VEO-IBD, bilateral sensorineural hearing loss, and impaired cytotoxic T-lymphocyte function (granule release, stimulated CD107a upregulation). Included on a monogenic IBD gene panel proposed by The Paediatric IBD Porto Group of ESPGHAN (PMID: 33346580).
Sources: Expert Review
Created: 29 Jan 2021, 4:47 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Very Early Onset Inflammatory Bowel Disease; Sensorineural hearing loss

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Very Early Onset Inflammatory Bowel Disease
  • Sensorineural hearing loss
OMIM
608339
Clinvar variants
Variants in STXBP3
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

9 Jun 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: stxbp3 has been classified as Amber List (Moderate Evidence).

9 Jun 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: STXBP3 were set to 33346580; https://doi.org/10.1053/j.gastro.2017.11.120

1 Feb 2021, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: stxbp3 has been classified as Amber List (Moderate Evidence).

1 Feb 2021, Gel status: 0

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: STXBP3 were set to PMID: 33346580

29 Jan 2021, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Kelsey Jones (Great Ormond Street Hospital)

gene: STXBP3 was added gene: STXBP3 was added to Primary immunodeficiency. Sources: Expert Review Mode of inheritance for gene: STXBP3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: STXBP3 were set to PMID: 33346580 Phenotypes for gene: STXBP3 were set to Very Early Onset Inflammatory Bowel Disease; Sensorineural hearing loss Penetrance for gene: STXBP3 were set to unknown Review for gene: STXBP3 was set to AMBER