1. Panels
  2. Fetal anomalies
  3. KIF21B
Genes in panel
Prev Next

Fetal anomalies

Gene: KIF21B

Amber List (moderate evidence)
KIF21B (kinesin family member 21B)
EnsemblGeneIds (GRCh38): ENSG00000116852
EnsemblGeneIds (GRCh37): ENSG00000116852
OMIM: 608322, Gene2Phenotype
KIF21B is in 2 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

This gene and phenotype were reviewed during meetings between November 2023 & July 2024. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler, Alison Male and Lyn Chitty (North Thames GLH), Stephanie Allen, Natalie Bibb, Esther Kinning and Denise Williams (Central & South GLH) and Natalie Canham, Anna De Burca and Samantha Doyle R21 Clinical Oversight Group.
Created: 29 Aug 2024, 8:33 p.m. | Last Modified: 29 Aug 2024, 8:33 p.m.
Panel Version: 4.36
Created: 29 Aug 2024, 8:33 p.m.
Last Modified: 29 Aug 2024, 8:33 p.m.
Panel version: 4.36

Natalie Chandler (North Thames GLH)

I don't know

Green in ID panel only. Asselin et al (2020 - PMID:32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD.2 with normal pregnacies, 2 with IUGR (1 with oligohydramnios). 2/4 abnormal MRI 1 ACC. Note that the 4bp del case had IUGR and abnormal MRI. Suggest amber as only 3 cases with GOF variants and limited phenotype that would present prenatally.
Created: 29 Aug 2024, 8:07 p.m. | Last Modified: 29 Aug 2024, 8:07 p.m.
Panel Version: 4.35

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Global developmental delay; Neurodevelopmental disorder, MONDO:0700092; Intellectual disability; Abnormality of brain morphology; Microcephaly

Publications

Created: 29 Aug 2024, 8:07 p.m.
Last Modified: 29 Aug 2024, 8:07 p.m.
Panel version: 4.35

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • NHS GMS
  • Expert Review Amber
Phenotypes
  • Global developmental delay
  • Neurodevelopmental disorder, MONDO:0700092
  • Intellectual disability
  • Abnormality of brain morphology
  • Microcephaly
OMIM
608322
Clinvar variants
Variants in KIF21B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 Aug 2024, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

gene: KIF21B was added gene: KIF21B was added to Fetal anomalies. Sources: Expert Review Amber,NHS GMS Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF21B were set to 32415109 Phenotypes for gene: KIF21B were set to Global developmental delay; Neurodevelopmental disorder, MONDO:0700092; Intellectual disability; Abnormality of brain morphology; Microcephaly