Intestinal failure or congenital diarrhoeaGene: STX3
This gene has been confirmed for this panel by the NHS Genomic Medicine Service and should be rated green.
Created: 8 Mar 2022, 11:44 a.m. | Last Modified: 8 Mar 2022, 11:44 a.m.
Panel Version: 1.48
Wiegerinck et al 2014 found homozygous truncating mutations in 2 consanguineous patients with MVID by exome sequencing. Western blot confirmed loss of protein expression in 1 case and mislocalisation of truncated protein in 2nd case. In vitro functional analysis showed statistically significant increase of both microvillus inclusions and basolateral microvilli and reduction of endogenous STX3 levels by overexpression of truncated, but not full-length, STX3 protein suggesting a dominant-negative effect.
Dhekne et al 2017: MYO5B, STX3, or STXBP2 encoded proteins all have roles in apical membrane trafficking in epithelial cells leading to suggestion that these three genes and their encoded proteins represent a common disease mechanism that unifies a subset of phenotypically linked congenital diarrheal disorders. They analyzed the subcellular distribution of syntaxin-3 and munc18-2 in enterocytes of intestinal biopsies from patients with MYO5B or STXBP2 mutations and found abnormal STX3 localisation. Authors say this provides compelling evidence that myosin Vb,syntaxin-3, and munc18-2 are functionally linked in human enterocytes, and likely comprise a common molecular pathway and disease mechanism that unifies a subgroup of congenital diarrheal disorders.
NOTE: PubMed: 25358429 identified homozygous missense STX3 mutation in a patient with autosomal recessive congenital cataract and intellectual disability phenotype without reported intestinal symptoms therefore milder mutations may be associated with alternate phenotype (similar to MYO5B missense mutations and cholestasis)
Created: 21 Jan 2019, 2:09 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Microvillus inclusion disease; congenital diarrheal disorder
Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.
Created: 31 Jan 2019, 10:55 a.m.
Initial gene list and info collated by Miranda Durkie Sheffield Diagnostic Genetics Service December 2018 on behalf of the GMS Gastrohepatology specialist test group. Gene Symbol submitted: STX3; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Created: 8 Jan 2019, 10:52 a.m.
Phenotypes for gene: STX3 were changed from Microvillus inclusion disease; congenital diarrheal disorder to Microvillus inclusion disease, MONDO:0009635; diarrheal disorder, MONDO:0001673
Gene: stx3 has been classified as Green List (High Evidence).
Publications for gene: STX3 were set to 24726755; 29266534; 25358429
Mode of inheritance for gene: STX3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STX3 were changed from to Microvillus inclusion disease; congenital diarrheal disorder
Publications for gene: STX3 were set to 24726755; 29266534
Publications for gene: STX3 were set to
Source Expert Review Green was added to STX3. Rating Changed from Red List (low evidence) to Green List (high evidence)
gene: STX3 was added gene: STX3 was added to Intestinal failure. Sources: NHS GMS Mode of inheritance for gene: STX3 was set to