SCYL1: A Pseudokinase Implicated in Neurological and Hepatic Disorders
Comprehensive genomic and proteomic overview of SCYL1, including its role in CALFAN syndrome and hepatocellular carcinoma.
Gene Information Card
| Symbol | SCYL1 |
|---|---|
| Full Name | SCYL1 pseudokinase |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 57410 ncbi.nlm.nih.gov/gene/57410 |
| Ensembl ID | ENSG00000142188 |
| UniProt ID | Q9Y6N5 |
| OMIM ID | 607982 |
| HGNC ID | 14373 |
| Aliases | NTKL, TEIF, SCYL1BP1 |
Description
SCYL1 (SCY1-like pseudokinase 1) encodes a member of the SCY1-like family of pseudokinases. The protein localizes to the Golgi apparatus and is involved in intracellular trafficking, nuclear transport, and cell cycle regulation. Mutations in SCYL1 cause CALFAN syndrome (cerebellar ataxia, liver fibrosis, and axonal neuropathy). The gene is also implicated in hepatocellular carcinoma through its interaction with the telomerase complex.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| CALFAN syndrome (Cerebellar Ataxia, Liver Fibrosis, Axonal Neuropathy) | Biallelic loss-of-function mutations in SCYL1 disrupt Golgi trafficking and nuclear transport, leading to neurodegeneration and hepatic fibrosis. | OMIM #618571; ClinVar |
| Hepatocellular carcinoma | SCYL1 (TEIF) overexpression or aberrant splicing may activate telomerase (hTERT) transcription, contributing to oncogenesis. | COSMIC; PubMed studies |
| Autosomal recessive spinocerebellar ataxia (SCAR) | SCYL1 mutations cause a subtype of spinocerebellar ataxia with liver involvement. | OMIM #618571 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Cerebellum | 10.8 | Medium |
| Cerebral cortex | 8.5 | Medium |
| Testis | 7.2 | Low |
| Kidney | 6.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 14.5 | High expression |
| SH-SY5Y (neuroblastoma) | 11.2 | Moderate expression |
| HeLa (cervical cancer) | 9.8 | Moderate expression |
| K562 (leukemia) | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.169C>T (p.Arg57*) | Nonsense | Rare (found in CALFAN families) | Loss of function; premature stop codon leads to nonsense-mediated decay. |
| c.892C>T (p.Arg298Trp) | Missense | Rare | Loss of function; disrupts kinase-like domain and Golgi localization. |
| c.1171C>T (p.Arg391*) | Nonsense | Rare | Loss of function; truncation of C-terminal domain. |
| c.1543C>T (p.Arg515*) | Nonsense | Rare | Loss of function; truncation of C-terminal domain. |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, missense) in SCYL1 cause CALFAN syndrome by impairing Golgi trafficking and nuclear transport.
Gain of Function (GOF)
Not established; overexpression of SCYL1 (TEIF) in hepatocellular carcinoma may represent a gain-of-function in telomerase activation, but no activating mutations are reported.
Dominant Negative (DN)
Not reported; all disease-associated mutations are recessive.
View complete mutation data：
Gene Ontology (GO)
| • Golgi apparatus | • protein transport |
| • nuclear transport | • pseudokinase activity |
| • cell cycle regulation | • telomerase activity |
Pathways
• Golgi vesicle transport
• Nuclear import/export
• Telomerase regulation
Protein Summary
SCYL1 is a 105 kDa pseudokinase that localizes to the Golgi apparatus. It contains an N-terminal kinase-like domain (catalytically inactive) and a C-terminal coiled-coil domain. The protein interacts with importin α and the COPI complex, regulating nuclear transport and Golgi trafficking. In hepatocellular carcinoma, SCYL1 (also known as TEIF) binds to the hTERT promoter to activate telomerase expression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SCYL1 Knockout HEK293 Cell Line | EDJ-KQ15204 | Human | 57410 | Details Get a Quote |
| SCYL1 Knockout A-549 Cell Line | EDJ-KQ45844 | Human | 57410 | Details Get a Quote |
| SCYL1 Knockout HCT 116 Cell Line | EDJ-KQ45845 | Human | 57410 | Details Get a Quote |
| SCYL1 Knockout HeLa Cell Line | EDJ-KQ45846 | Human | 57410 | Details Get a Quote |
