Intellectual disability - microarray and sequencing
Gene: SHANK1This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:34113010 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tagCreated: 16 Oct 2023, 8:11 p.m. | Last Modified: 16 Oct 2023, 8:11 p.m.
Panel Version: 5.313
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.
Panel Version: 5.286
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Comment on list classification: There is sufficient evidence (at least four unrelated cases) for this gene to be promoted to GREEN at the next major review.Created: 17 Apr 2023, 11:23 a.m. | Last Modified: 17 Apr 2023, 11:23 a.m.
Panel Version: 5.57
As reviewed by Zornitza Stark (Australian Genomics), PMID:34113010 reported six unrelated individuals who presented with neurodevelopmental disorders and identified with de novo truncating variants in SHANK1 gene. Of these six individuals, four had intellectual disability, one had severe learning difficulties and one with auditory processing disorder, difficulty with executive functioning, mathematic concepts, verbal reasoning and problem solving. Three of these patients were also reported with autism spectrum disorder.
This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'strong' rating in the DD panel).Created: 17 Apr 2023, 11:15 a.m. | Last Modified: 17 Apr 2023, 11:20 a.m.
Panel Version: 5.54
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Publications
May et al. (2021) reported 6 individuals with developmental delay and autism with de novo truncating variants detected via WES. Evaluation of NMD resulted in stable transcripts, and the truncated SHANK1 completely lost binding with Homer1, a linker protein that binds to the C-terminus of SHANK1. Dispersed localization of the truncated SHANK1 variants within the spine and dendritic shaft was observed when expressed in neurons, indicating impaired synaptic localization of truncated SHANK1.
Also >10 individuals reported in autism cohorts +/- ID.Created: 11 Oct 2021, 10 a.m. | Last Modified: 11 Oct 2021, 10 a.m.
Panel Version: 3.1338
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Neurodevelopmental disorder
Publications
There is currently no evidence to suggest there is an association of this gene with intellectual disability. A number of papers with knockout mice implicate SHANK1 plays a role in learning and cognition but no evidence in humans.Created: 5 Aug 2019, 10:14 a.m. | Last Modified: 5 Aug 2019, 10:14 a.m.
Panel Version: 2.993
Publications
This gene has no OMIM disorder listed against it. There are 2 'Green' reviews listed against this gene for ID panel, but with no supporting evidence - what is the evidence for its inclusion as a Green gene?Created: 23 Jul 2019, 12:53 p.m. | Last Modified: 23 Jul 2019, 12:53 p.m.
Panel Version: 2.967
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
AUTISM
Publications
Tag gene-checked tag was added to gene: SHANK1.
Tag Q2_23_promote_green was removed from gene: SHANK1.
Source NHS GMS was added to SHANK1. Source Expert Review Green was added to SHANK1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_23_promote_green tag was added to gene: SHANK1.
Gene: shank1 has been classified as Amber List (Moderate Evidence).
Gene: shank1 has been classified as Amber List (Moderate Evidence).
Gene: shank1 has been classified as Amber List (Moderate Evidence).
Gene: shank1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: SHANK1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: SHANK1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: SHANK1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: SHANK1 were changed from AUTISM to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Publications for gene: SHANK1 were set to 0
Gene: shank1 has been classified as Red List (Low Evidence).
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
SHANK1 was created by ellenmcdonagh
SHANK1 was added to Intellectual disabilitypanel. Sources: Expert Review Green