KATNAL2
  • 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
KATNAL2 (HGNC:25387) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
katanin catalytic subunit A1 like 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
MGC33211, DKFZP667C165
%HI
41.98(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
1.1(Read more about gnomAD LOEUF score)
Cytoband
18q21.1
Genomic Coordinates
GRCh37/hg19: chr18:44497557-44628614 NCBI Ensembl UCSC
GRCh38/hg38: chr18:46917594-47102243 NCBI Ensembl UCSC
MANE Select Transcript
NM_001387690.1 ENST00000683218.1 (Read more about MANE Select)
Function
Severs microtubules in vitro in an ATP-dependent manner. This activity may promote rapid reorganization of cellular microtubule arrays. {ECO:0000255|HAMAP-Rule:MF_03025}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-16142
ClinGen Curation ID:
CCID:007349
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
11/28/2018

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 22495311
    Neale et al (2012) completed exome sequencing of 175 autism trios and identified de novo variants. One candidate gene identified was KATNAL2. They evaluated strong candidates further using exome sequencing on 935 cases and 870 controls, and at KATNAL2, three additional loss-of-function mutations were observed in cases with none in controls. However, using data from more than 5,000 individuals in the NHLBI Exome Variant Server (http://evs.gs.washington.edu/EVS/) as additional controls, three loss-of-function mutations were seen in KATNAL2. Nonetheless, the authors suggest that results from de novo events and a large parallel case–control study provide strong evidence in favour of KATNAL2 as genuine autism risk factor, acknowledging that additional variants may be required to express the phenotype.
  • PUBMED: 22495309
    O'Roak et al (2012) completed exome sequencing Simons Simplex Collection trios (189 new trios and 20 that were previously reported). Additionally, they also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. They detected one de novo splice mutation in KATNAL2 in this cohort.
  • PUBMED: 28191889
    Stessman et al (2017) sequenced 208 candidate genes from >11,730 cases from the Autism Genetic Resource Exchange (AGRE) and >2,867 controls. They identified a de novo loss-of-function variant and a likely damaging de novo missense variant in KATNAL2.
HI Evidence Comments:
Neurodevelopmental delay, including autism spectrum disorder, schizophrenia Two groups (Sanders et al (2012) and O`Roak et al (2012)) performed whole exome sequencing of Simons Simplex Collection (SSC) cases of well-phenotyped individuals with autism spectrum disorder. From a total of 414 non-overlapping probands, two de novo potentially-disruptive splice-site variants were detected at KATNAL2. These results were replicated in additional analyses of the SSC cohort (Iossifov et al ,2015, PMID: 25363768). Additional, de novo potentially-disruptive variants have been detected to be enriched in cases by Stessman et al (2017) and Neale et al (2012) in independent cohorts, though Neale et al also detected three loss-of-function mutations at KATNAL2 from more than 5,000 control individuals in the NHLBI Exome Variant Server (http://evs.gs.washington.edu/EVS/). Yuen et al (2015) completed whole-genome sequencing (WGS) of 85 quartet families (parents and two ASD-affected siblings), consisting of 170 individuals with ASD. They identified one maternally-inherited, nonsense mutation in KATNAL2 that was present in one of two siblings with ASD (PMID:25621899). Likely disruptive variants in KATNAL2 appear to be associated with risk for autism spectrum disorder, however variable penetrance/expressivity may occur as evidenced by the presence of loss-of-function variants in controls and unaffected/sub-clinically affected relatives.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000018.9) (NC_000018.10)