CMT-SCYL1

Genetic Context

HGNC-Approved Gene Symbol

SCYL1

Gene Full Name

SCY1 like pseudokinase 1

HGNC Gene Alias(es)

NTKL

Chromosome

11q13.1

Zygosity of Responsible Variant

Homozygous

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Complete loss

Confidence:
High

Prediction:
Human null alleles and a long-studied mouse converge on biallelic loss of function for CMT-SCYL1: SCYL1 encodes a catalytically inactive pseudokinase that binds COPI coat components and supports retrograde Golgi-to-endoplasmic-reticulum traffic. Recessive nonsense, frameshift, and splice variants remove it, and the spontaneously arising Scyl1-deficient mdf mouse develops motor neuron degeneration from the same absence of protein. Affected individuals present with the CALFAN combination of cholestatic liver episodes, ataxia, and CMT.

Rationale:
Truncating alleles spread across the gene produce one phenotype, and the mdf mouse arrives at it by losing the protein entirely, so disease tracks absent SCYL1 rather than any property of a mutant version. Motor neurons are the vulnerable cell type because retrograde traffic sustains the longest secretory routes in the body.

ClinVar Pathogenic Variants

View SCYL1 ClinVar Variants

SCYL1 OMIM Entry

SCYL1 OMIM