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Intellectual disability

Gene: CRNKL1

Green List (high evidence)
CRNKL1 (crooked neck pre-mRNA splicing factor 1)
EnsemblGeneIds (GRCh38): ENSG00000101343
EnsemblGeneIds (GRCh37): ENSG00000101343
OMIM: 610952, Gene2Phenotype
CRNKL1 is in 4 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 12 Mar 2026, 1:33 p.m. | Last Modified: 12 Mar 2026, 1:33 p.m.
Panel Version: 9.299
Created: 12 Mar 2026, 1:33 p.m.
Last Modified: 12 Mar 2026, 1:33 p.m.
Panel version: 9.299

Ida Ertmanska (Genomics England Curator)

Comment on phenotypes: OMIM phenotype added 26th Jan 2026.
Created: 30 Jan 2026, 11:44 a.m. | Last Modified: 30 Jan 2026, 11:44 a.m.
Panel Version: 9.243
Created: 30 Jan 2026, 11:44 a.m.
Last Modified: 30 Jan 2026, 11:44 a.m.
Panel version: 9.243

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

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, 3:31 p.m. | Last Modified: 9 Jul 2025, 3:31 p.m.
Panel Version: 9.32
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: Literature
Created: 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

Created: 9 Jul 2025, 3:29 p.m.

Panel version: 9.31

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • NHS GMS
  • Literature
Phenotypes
  • Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia, OMIM:621436
  • complex neurodevelopmental disorder, MONDO:0100038
OMIM
610952
Clinvar variants
Variants in CRNKL1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Mar 2026, Gel status: 3

Removed Tag, Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag dd_review was removed from gene: CRNKL1. Tag Q3_25_promote_green was removed from gene: CRNKL1.

12 Mar 2026, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to CRNKL1. Source Expert Review Green was added to CRNKL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

30 Jan 2026, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: CRNKL1 were changed from Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia, OMIM:621436; complex neurodevelopmental disorder, MONDO:0100038 to Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia, OMIM:621436; complex neurodevelopmental disorder, MONDO:0100038

30 Jan 2026, Gel status: 2

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: CRNKL1 were set to https://doi.org/10.1016/j.ajhg.2025.05.013

30 Jan 2026, Gel status: 2

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

21 Jul 2025, Gel status: 2

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag dd_review tag was added to gene: CRNKL1.

9 Jul 2025, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: crnkl1 has been classified as Amber List (Moderate Evidence).

9 Jul 2025, Gel status: 1

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_25_promote_green tag was added to gene: CRNKL1.

9 Jul 2025, Gel status: 1

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 Intellectual disability. 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