Severe microcephaly
Gene: INTS11EnsemblGeneIds (GRCh38): ENSG00000127054
EnsemblGeneIds (GRCh37): ENSG00000127054
OMIM: 611354, Gene2Phenotype
INTS11 is in 5 panels
3 reviews
Sarah Leigh (Genomics England Curator)
The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 2:56 p.m. | Last Modified: 10 Oct 2023, 2:56 p.m.
Panel Version: 4.33
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Arina Puzriakova (Genomics England Curator)
Additional case identified at a NHS Genomic Laboratory Hub (GLH) with compound heterozygous variants in this gene. Phenotypic features include cognitive impairment, ataxia, aplasia/hypoplasia of the cerebellum, hyperreflexia, babinski sign.Created: 22 May 2023, 2:59 p.m. | Last Modified: 22 May 2023, 2:59 p.m.
Panel Version: 5.150
Achchuthan Shanmugasundram (Genomics England Curator)
Comment on list classification: There is sufficient evidence (10 unrelated cases and supporting functional evidence) for this gene to be promoted to green at the next major review.Created: 26 Apr 2023, 3:09 p.m. | Last Modified: 26 Apr 2023, 3:09 p.m.
Panel Version: 5.69
PMID:37054711 reported ten unrelated families with biallelic variants in INTS11 gene and they present with intellectual disability, global developmental and language delay, impaired motor development, and brain atrophy.
Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages. In addition, genes with two variants (p.Arg17Leu and p.His414Tyr) fail to rescue the lethality of null mutants in the Drosophila model, indicating that they are strong loss-of-function variants. The other five variants (p.Gly55Ser, p.Leu138Phe, p.Lys396Glu, p.Val517Met and p.Ile553Glu) rescue lethality but cause a shortened lifespan and bang sensitivity and affect locomotor activity, indicating that they are partial loss-of-function variants.
This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: LiteratureCreated: 26 Apr 2023, 3:07 p.m. | Last Modified: 26 Apr 2023, 3:11 p.m.
Panel Version: 5.70
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
intellectual disability, MONDO:0001071
Publications
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- NHS GMS
- Expert Review Green
- Literature
- Phenotypes
-
- Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428
- OMIM
- 611354
- Clinvar variants
- Variants in INTS11
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Set Phenotypes
Arina Puzriakova (Genomics England Curator)Phenotypes for gene: INTS11 were changed from Complex neurodevelopmental disorder, MONDO:0100038 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428
Removed Tag
Sarah Leigh (Genomics England Curator)Tag Q2_23_promote_green was removed from gene: INTS11.
Added New Source, Added New Source, Status Update
Sarah Leigh (Genomics England Curator)Source Expert Review Green was added to INTS11. Source NHS GMS was added to INTS11. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes
Arina Puzriakova (Genomics England Curator)gene: INTS11 was added gene: INTS11 was added to Severe microcephaly. Sources: Expert Review Amber,Literature Q2_23_promote_green tags were added to gene: INTS11. Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INTS11 were set to 37054711 Phenotypes for gene: INTS11 were set to Complex neurodevelopmental disorder, MONDO:0100038