SCYL1

Chr 11AR

SCY1 like pseudokinase 1

Also known as: GKLP, HT019, NKTL, NTKL, P105, SCAR21, TAPK, TEIF

NCBI Gene: 57410ENSG00000142186UniProt: Q96KG9

This gene encodes a transcriptional regulator belonging to the SCY1-like family of kinase-like proteins. The protein has a divergent N-terminal kinase domain that is thought to be catalytically inactive, and can bind specific DNA sequences through its C-terminal domain. It activates transcription of the telomerase reverse transcriptase and DNA polymerase beta genes. The protein has been localized to the nucleus, and also to the cytoplasm and centrosomes during mitosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia, autosomal recessive 21MIM #616719
AR
313
ClinVar variants
43
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— SCYL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 144 VUS of 313 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.68LOEUF
pLI 0.000
Z-score 3.25
OE 0.47 (0.33–0.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.33Z-score
OE missense 0.83 (0.77–0.90)
405 obs / 487.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.33–0.68)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.90)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 20 / 43.0Missense obs/exp: 405 / 487.8Syn Z: -0.06

ClinVar Variant Classifications

313 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic16
VUS144
Likely Benign83
Benign13
Conflicting4
27
Pathogenic
16
Likely Pathogenic
144
VUS
83
Likely Benign
13
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
3
14
0
27
Likely Pathogenic
8
2
5
1
16
VUS
0
136
7
1
144
Likely Benign
0
17
24
42
83
Benign
0
2
5
6
13
Conflicting
—4
Total181605550287

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SCYL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SCYL1-related episodes of liver failure, peripheral neuropathy, cerebellar atrophy, and ataxia

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SCY1-LIKE 1; SCYL1
MIM #607982 · *

Spinocerebellar ataxia, autosomal recessive 21

MIM #616719

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SCYL1-mediated regulation of the mTORC1 signaling pathway inhibits autophagy and promotes gastric cancer metastasis.
Zhao Z et al.·J Cancer Res Clin Oncol
2024
Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency.
Peters B et al.·J Inherit Metab Dis
2025Review
Mutations in NBAS and SCYL1, genetic causes of recurrent liver failure in children: Three case reports and a literature review.
Chavany J et al.·Arch Pediatr
2020Review
Overexpression of SCYL1 Is Associated with Progression of Breast Cancer.
Sun A et al.·Curr Oncol
2022
Hereditary ataxias and paraparesias: clinical and genetic update.
Parodi L et al.·Curr Opin Neurol
2018Review
SCYL1 disease and liver transplantation diagnosed by reanalysis of exome sequencing and deletion/duplication analysis of SCYL1.
McNiven V et al.·Am J Med Genet A
2021
Variant in SCYL1 gene causes aberrant splicing in a family with cerebellar ataxia, recurrent episodes of liver failure, and growth retardation.
Shohet A et al.·Eur J Hum Genet
2019Case report
Phenotype and Long-Term Outcome in Recurrent Paediatric Acute Liver Failure: Systematic Review and Individual Participant Data Analysis.
Sutton H et al.·Liver Int
2025Review
SCYL1 variants cause a syndrome with low γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration (CALFAN).
Lenz D et al.·Genet Med
2018
SCYL1 deficiency: A rare entity with challenging neurological manifestations after liver transplantation.
Warasnhe K et al.·Pediatr Transplant
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SCYL1 deficiency in CALFAN syndrome is associated with ER stress and cell death.
Hellicar J et al.·Dis Model Mech
2025🔓 Open Access
SCYL1 deficiency and intrafamilial variability: Two cases from Kuwait.
Kazem L et al.·Mol Genet Metab Rep
2025🔓 Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Chronic Obstructive Pulmonary Disease Exacerbation

The CATALINA Study

RECRUITING
NCT05008081Wim JanssensStarted 2022-10-25

External Resources

Links to major genomics databases and tools