Hereditary Neuropathy - complex

Gene: KARS

Amber List (moderate evidence)

KARS (lysyl-tRNA synthetase)
EnsemblGeneIds (GRCh38): ENSG00000065427
EnsemblGeneIds (GRCh37): ENSG00000065427
OMIM: 601421, Gene2Phenotype
KARS is in 12 panels

1 review

Sangavi Sivagnanasundram (Melbourne Health)

I don't know

Only reported in one individual however functional analysis shows variants in KARS could be important for a diagnosis of CMT.

PMID: 20920668
Genes encoding aminoacyl-tRNA synthetases (ARS) are known to be causative of Charcot Marie Tooth.
Reported one individual with an intermediate CMT phenotype with peripheral neuropathy.
The individual was a compound heterozygote (p.Leu133His; p.Tyr173SerfsX7).
Structural functional analysis on the ARAS enzyme showed the frameshift mutation is predicted to result in a complete loss of function of the catalytic domain.
In vitro functional assay using human cytoplasmic tRNA was synthesised. The functional assay showed the p.Leu133His variant severely impairs enzyme activity resulting in >90% of the catalytic efficiency.
Created: 13 Jul 2023, 11:40 p.m. | Last Modified: 13 Jul 2023, 11:40 p.m.
Panel Version: 0.169

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Charcot-Marie-Tooth disease, recessive intermediate, B (MIM#613641; MONDO:0013338)

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Royal Melbourne Hospital
Phenotypes
  • Charcot-Marie-Tooth disease, recessive intermediate, B (MIM#613641
  • MONDO:0013338)
OMIM
601421
Clinvar variants
Variants in KARS
Penetrance
None
Publications
Panels with this gene

History Filter Activity

24 Jul 2023, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

24 Jul 2023, Gel status: 2

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: KARS were changed from HMSN; Charcot Marie Tooth disease, recessive intermediate, B, 613641; Deafness, autosomal recessive 89, 613916 to Charcot-Marie-Tooth disease, recessive intermediate, B (MIM#613641; MONDO:0013338)

24 Jul 2023, Gel status: 2

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: KARS were set to

24 Jul 2023, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

13 Jan 2020, Gel status: 3

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

Bryony Thompson (Royal Melbourne Hospital)

gene: KARS was added gene: KARS was added to Hereditary Neuropathy - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: KARS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: KARS were set to HMSN; Charcot Marie Tooth disease, recessive intermediate, B, 613641; Deafness, autosomal recessive 89, 613916