Severe microcephaly
Gene: CRNKL1EnsemblGeneIds (GRCh38): ENSG00000101343
EnsemblGeneIds (GRCh37): ENSG00000101343
OMIM: 610952, Gene2Phenotype
CRNKL1 is in 4 panels
2 reviews
Ida Ertmanska (Genomics England Curator)
Comment on phenotypes: OMIM phenotype added 30th Jan 2026.Created: 30 Jan 2026, 11:42 a.m. | Last Modified: 30 Jan 2026, 11:42 a.m.
Panel Version: 8.29
Achchuthan Shanmugasundram (Genomics England Curator)
Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.Created: 9 Jul 2025, 3:34 p.m. | Last Modified: 9 Jul 2025, 3:34 p.m.
Panel Version: 8.4
There are 10 unrelated patents identified with de novo missense variants in the spliceosomal component CRNKL1, where nine of them harboured one of the two missense variants affecting the same amino acid residue, Arg 267 (p.Arg267Cys & p.Arg267His), while the tenth patient harboured a different variant (p.Arg301Gly). All affected individuals share a common and specific phenotype: profound pre- and post-natal microcephaly (8 of 10 patients), with pontocerebellar hypoplasia (9 patients), seizures (8 patients), and severe intellectual disability (8 patients).
Microinjection of mRNA encoding Crnkl1 variant into a zebrafish model caused a severe lack of brain development accompanied by a significant reduction in proliferating cells and widespread cellular stress, as indicated by p53 staining. RNA sequencing analysis of injected zebrafish embryos showed broad transcriptomic changes, with altered expression of neuronal and cell cycle genes.
This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: LiteratureCreated: 9 Jul 2025, 3:29 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
complex neurodevelopmental disorder, MONDO:0100038
Publications
- https://doi.org/10.1016/j.ajhg.2025.05.013
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Amber
- Literature
- Phenotypes
-
- Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia, OMIM:621436
- complex neurodevelopmental disorder, MONDO:0100038
- Tags
- OMIM
- 610952
- Clinvar variants
- Variants in CRNKL1
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Set publications
Ida Ertmanska (Genomics England Curator)Publications for gene: CRNKL1 were set to https://doi.org/10.1016/j.ajhg.2025.05.013
Set Phenotypes
Ida Ertmanska (Genomics England Curator)Phenotypes for gene: CRNKL1 were changed from complex neurodevelopmental disorder, MONDO:0100038 to Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia, OMIM:621436; complex neurodevelopmental disorder, MONDO:0100038
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag dd_review tag was added to gene: CRNKL1.
Entity classified by Genomics England curator
Achchuthan Shanmugasundram (Genomics England Curator)Gene: crnkl1 has been classified as Amber List (Moderate Evidence).
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q3_25_promote_green tag was added to gene: CRNKL1.
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)gene: CRNKL1 was added gene: CRNKL1 was added to Severe microcephaly. Sources: Literature Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CRNKL1 were set to https://doi.org/10.1016/j.ajhg.2025.05.013 Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder, MONDO:0100038 Review for gene: CRNKL1 was set to GREEN