SCYL1

Chr 11AR

SCY1 like pseudokinase 1

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

NCBI Gene: 57410 ENSG00000142186 UniProt: Q96KG9 OMIM: 607982

This protein functions as a transcriptional regulator that activates telomerase reverse transcriptase and DNA polymerase beta genes, and regulates COPI-mediated retrograde protein traffic between the Golgi apparatus and endoplasmic reticulum. Mutations cause spinocerebellar ataxia, autosomal recessive 21, which follows autosomal recessive inheritance. The gene shows relatively low constraint to loss-of-function variation (pLI near zero, LOEUF 0.677).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.681 OMIM phenotype

Clinical Summary— SCYL1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

35 unique Pathogenic / Likely Pathogenic· 140 VUS of 301 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.000

Z-score 3.25

OE 0.47 (0.33–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.33Z-score

OE missense 0.83 (0.77–0.90)

405 obs / 487.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.33–0.68)

0≤0.351.4

Missense OE?0.83 (0.77–0.90)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 20 / 43.0Missense obs/exp: 405 / 487.8Syn Z: -0.06

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongSCYL1-related episodes of liver failure, peripheral neuropathy, cerebellar atrophy, and ataxiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6355th %ile

GOF

0.5955th %ile

LOF

0.3549th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

301 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic14

VUS140

Likely Benign85

Benign12

Conflicting4

Pathogenic

Likely Pathogenic

140

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	18	3	0	0	21
Likely Pathogenic	11	2	0	1	14
VUS	0	137	2	1	140
Likely Benign	0	18	23	44	85
Benign	0	2	5	5	12
Conflicting	—				4
Total	29	162	30	51	276

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap SCYL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →