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Intellectual disability

Gene: KATNB1

Amber List (moderate evidence)

KATNB1 (katanin regulatory subunit B1)
EnsemblGeneIds (GRCh38): ENSG00000140854
EnsemblGeneIds (GRCh37): ENSG00000140854
OMIM: 602703, Gene2Phenotype
KATNB1 is in 5 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Amber. Gene was added to the ID panel and rated Green by Konstantinos Varvagiannis. Although there are 3 publications reporting biallelic variants, the ID phenotype is variable with only mild cognitive delay in some cases (PMID:25521378), and psychomotor delay in another (PMID:26640080). KATNB1 is Green on the 'malformations of cortical development' panel. Therefore have rated Amber on the ID panel awaiting further cases.
Created: 21 Sep 2019, 9:18 a.m. | Last Modified: 21 Sep 2019, 9:18 a.m.
Panel Version: 2.1046
Summary of evidence (for details refer to Konstantinos Varvagiannis' review): 3 publications reporting patients with biallelic KATNB1 variants:

PMID:25521378. Mishra-Gorur et al. 2014 report 5 families with malformations of cortical development and homozygous KATNB1 variants. In many families homozygous variants in additional genes were also reported. Congnitive delay was mild to severe in all patients: Supplementary Table S1.

PMID:25521379. Hu et al., 2014 report 3 unrelated Middle Eastern families with microcephaly, Global DD and seizures, and 3 different homozygous variants in KATNB1.

PMID:26640080. Yigit el al. 2016 report a homozygous acceptor splice-site intronic KATNB1 variant in a 5 year old Turkish girl born to consanguineous cousins, who presented with congenital microcephaly, lissencephaly, short stature, polysyndactyly, dental abnormalities and psychomotor delay.
Created: 21 Sep 2019, 9:14 a.m. | Last Modified: 21 Sep 2019, 9:14 a.m.
Panel Version: 2.1044

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Biallelic pathogenic KATNB1 variants cause Lissencephaly 6, with microcephaly (MIM 616212). At least 13 affected individuals from 9 (mostly consanguineous) families have probably been reported in the following articles:

- Mishra-Gorur et al. (2014 - PMID: 25521378) [7 individuals from 5 unrelated families]
- Hu et al. (2014 - PMID: 25521379) [5 individuals from 3 families]
- Yigit el al. (2016 - PMID: 26640080) [1 subject born to consanguineous parents]

The phenotype appears to be relevant to the current panel. Several different variants have been reported to date. Extensive studies as for the impact of mutations at the cellular level as well as animal models (zebrafish, mouse, drosophila) support involvement of KATNB1. These arguments, provided mainly by the first two studies, are summarized in the respective OMIM entry for the disorder : (variants and their effect are discussed in the entry for KATNB1 -

The individual reported by Yigit el al. was a 5 year-old girl with - among others - severely delayed psychomotor development. The child was found to harbor a homozygous splice site variant (removing the acceptor AG signature). Confirmation of the variant and segregation studies were performed with Sanger sequencing. cDNA studies were carried out and demonstrated aberrant splicing.

KATNB1 is not associated with any disorder in G2P.
The gene is included in panels for ID offered by several diagnostic laboratories (incl. Radboudumc).

As a result, this gene can be considered for inclusion in the current panel probably as green (or amber).
Sources: Literature, Radboud University Medical Center, Nijmegen
Created: 31 Aug 2019, 10:46 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Lissencephaly 6, with microcephaly (MIM 616212)


Variants in this GENE are reported as part of current diagnostic practice


Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Amber
  • Lissencephaly 6, with microcephaly, OMIM:616212, MONDO:0014534
Clinvar variants
Variants in KATNB1
Panels with this gene

History Filter Activity

29 Jan 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly, MIM 616212 to Lissencephaly 6, with microcephaly, OMIM:616212, MONDO:0014534

21 Sep 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: katnb1 has been classified as Amber List (Moderate Evidence).

21 Sep 2019, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly (MIM 616212) to Lissencephaly 6, with microcephaly, MIM 616212

31 Aug 2019, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: KATNB1 was added gene: KATNB1 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: KATNB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KATNB1 were set to 25521378; 25521379; 26640080 Phenotypes for gene: KATNB1 were set to Lissencephaly 6, with microcephaly (MIM 616212) Penetrance for gene: KATNB1 were set to Complete Review for gene: KATNB1 was set to GREEN gene: KATNB1 was marked as current diagnostic