Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: HSPA1L
The variants identified are present at relatively high frequencies in gnomad V4, in particular p.Thr267Ile is present in 281 individuals, and the p.Ala268Thr is present in 4,753 individuals.
These observations raise concerns about pathogenicity under a monogenic disease model.Created: 15 Feb 2024, 10:49 p.m. | Last Modified: 15 Feb 2024, 10:49 p.m.
Panel Version: 4.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
inflammatory bowel disease, MONDO:0005265, HSPA1L-related
Comment on list classification: There is sufficient evidence available (seven unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS review.Created: 14 Feb 2024, 3:55 p.m. | Last Modified: 14 Feb 2024, 3:55 p.m.
Panel Version: 4.182
As reviewed by Hannah Knight, PMID:28126021 reported the identification of a heterozygous de novo variant (p.Ser277Leu) in HSPA1L in a patient with inflammatory bowel disease. In addition, five additional rare HSPA1L variants (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) were identified in six patients from a cohort of 136 IBD patients with WES data.
Functional studies showed that all six HSPA1L variant proteins showed decreased chaperone activity in vitro. Moreover, three variants demonstrated dominant negative effects on HSPA1L and HSPA1A protein activity.
This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.Created: 14 Feb 2024, 3:52 p.m. | Last Modified: 14 Feb 2024, 3:52 p.m.
Panel Version: 4.179
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
inflammatory bowel disease, MONDO:0005265
Publications
PMID: 28126021 (2017) identified a heterozygous de novo variant (c.830C > T; p.Ser277Leu) in HSPA1L in a patient with IBD + some in vitro testing which supported pathogenicity
Then identified five additional rare HSPA1L variants (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) in six patients from their IBD cohort
Sources: LiteratureCreated: 13 Feb 2024, 10:26 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Inflammatory bowel disease
Publications
Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: HSPA1L were changed from Inflammatory bowel disease to inflammatory bowel disease, MONDO:0005265
Publications for gene: HSPA1L were set to PMID: 28126021
Tag Q1_24_promote_green tag was added to gene: HSPA1L. Tag Q1_24_NHS_review tag was added to gene: HSPA1L.
gene: HSPA1L was added gene: HSPA1L was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: HSPA1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HSPA1L were set to PMID: 28126021 Phenotypes for gene: HSPA1L were set to Inflammatory bowel disease Review for gene: HSPA1L was set to AMBER