Cholestasis

Gene: SCYL1

Green List (high evidence)

Comment on list classification: As reviewed by Karen Stals, biallelic mutations in SCYL1 were reported in at least 7 pedigrees where affected individuals presented with acute liver failure with onset in infancy / early childhood. Based on available evidence, this gene should be promoted to Green for Cholestasis.

Created: 21 Jan 2026, 2 p.m. | Last Modified: 21 Jan 2026, 2 p.m.

Panel Version: 3.16

PMID: 33442927 - 13-year-old boy and 9-year-old girl siblings with acute liver insufficiency and underwent liver transplantation in infancy; acute liver failure at 5 months in both; other symptoms: tremor, global developmental delay, and cognitive dysfunction; compound het for SCYL1 c.399delC; p.Asn133Lysfs*136 and SCYL1 exon 7-8 deletion (confirmed in trans).

PMID: 30842961 - Han Chinese boy with fever-associated recurrent acute liver failure, onset at age 14 mo. Bilateral femoral head abnormalities and mild impairment of neurologic function noted around 8yo. Liver biopsy at ages 7 and 8 yo found abnormal architecture and hepatic fibrosis, respectively. Homozygous for SCYL1 c.92_93insGGGCCCT, p.(H32Gfs*20) - WES, parents confirmed het.

PMID: 29419818 - Seven patients from 5 families with biallelic SCYL1 variants. The main clinical phenotype was recurrent low γ-glutamyl-transferase (GGT) cholestasis or acute liver failure with onset in infancy and a variable neurological phenotype of later onset.

SCYL1 is associated with Spinocerebellar ataxia, autosomal recessive 21, MIM:616719 in OMIM, also known as 'low gammaglutamyltransferase (GGT) cholestasis, acute liver failure, and neurodegeneration (CALFAN) syndrome' (OMIM accessed 21st Jan 2026).

Created: 21 Jan 2026, 1:52 p.m. | Last Modified: 21 Jan 2026, 1:52 p.m.

Panel Version: 3.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
cholestasis, MONDO:0001751; acute liver failure, MONDO:0019542; Spinocerebellar ataxia, autosomal recessive 21, OMIM:616719

Publications

• 29419818
• 30842961
• 33442927

Green List (high evidence)

Multiple patients reported with biallelic variants in SCYL1, early presentation of liver failure and cholestasis in infancy (episodes may resolve), with later development of a neurological phenotype.
Sources: Literature

Created: 12 Jan 2026, 11:31 a.m. | Last Modified: 12 Jan 2026, 11:31 a.m.

Panel Version: 3.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Liver failure; cholestasis; ataxia; peripheral neuropathy; cerebellar atrophy

Publications

• PMID: 30842961
• PMID: 33442927
• PMID: 30842961
• PMID: 29419818

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