SCYL1

SCY1 like pseudokinase 1, the group of Armadillo like helical domain containing|SCY1 like pseudokinases

Basic information

Region (hg38): 11:65525076-65538704

Previous symbols: [ "NTKL" ]

Links

ENSG00000142186 ∙ NCBI:57410 ∙ OMIM:607982 ∙ HGNC:14372 ∙ Uniprot:Q96KG9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (Strong), mode of inheritance: AR
• acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (Supportive), mode of inheritance: AR
• acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 21	AR	Gastrointestinal	Individuals have been described with childhood-onset acute liver failure, and awareness may allow surveillance and prompt management	Gastrointestinal; Neurologic	26581903

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCYL1 gene.

• not provided (60 variants)
• Inborn genetic diseases (46 variants)
• Acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (10 variants)
• SCYL1-related condition (3 variants)
• Spinocerebellar ataxia type 21 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCYL1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	18	7	26
missense		1	46	8	3	58
nonsense	2	1				3
start loss						0
frameshift	3	1				4
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	3				4
splice region			1	1	2	4
non coding				2	3	5
Total	6	6	48	28	13

Highest pathogenic variant AF is 0.00000657

Variants in SCYL1

This is a list of pathogenic ClinVar variants found in the SCYL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-65525182-G-A		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
11-65525203-T-C		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
11-65525204-C-T		SCYL1-related disorder	Likely benign (May 28, 2019)
11-65525227-T-C		Inborn genetic diseases	Likely benign (Aug 13, 2021)
11-65525564-C-T			Likely benign (Jul 21, 2023)
11-65525587-C-T		Inborn genetic diseases	Uncertain significance (Dec 04, 2023)
11-65525612-G-C			Likely benign (Aug 01, 2022)
11-65525631-C-T		CALFAN syndrome • Acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome	Pathogenic (Oct 11, 2019)
11-65525638-A-G		Inborn genetic diseases	Uncertain significance (Nov 08, 2021)
11-65525661-C-T		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)
11-65525730-C-T			Likely benign (Jan 13, 2024)
11-65525924-G-T		CALFAN syndrome	Pathogenic (Nov 09, 2017)
11-65525941-C-T			Likely benign (Mar 29, 2018)
11-65525974-C-T			Likely benign (Apr 01, 2023)
11-65525981-G-A		Inborn genetic diseases	Uncertain significance (Feb 26, 2024)
11-65525982-C-T		CALFAN syndrome • Acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome	Pathogenic (Oct 11, 2019)
11-65525983-G-A			Benign (Dec 31, 2019)
11-65525992-G-A			Benign (Jan 26, 2024)
11-65525996-G-A		Inborn genetic diseases	Uncertain significance (Aug 14, 2023)
11-65526041-G-A			Benign (Jan 12, 2024)
11-65526132-C-T		SCYL1-related disorder	Likely benign (Nov 07, 2023)
11-65526146-AC-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (May 01, 2019)
11-65526148-G-C		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
11-65526166-A-G		Inborn genetic diseases	Uncertain significance (Apr 24, 2022)
11-65526192-C-T			Likely benign (Jun 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCYL1	protein_coding	protein_coding	ENST00000270176	18	13628

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.52e-8	1.00	124778	0	51	124829	0.000204

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.33	405	488	0.830	0.0000299	5219
Missense in Polyphen		98	127.28	0.76996		1340
Synonymous	-0.0597	208	207	1.01	0.0000137	1624
Loss of Function	3.25	20	43.0	0.466	0.00000233	448

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000345	0.000345
Ashkenazi Jewish	0.00	0.00
East Asian	0.000223	0.000223
Finnish	0.000447	0.000417
European (Non-Finnish)	0.000214	0.000212
Middle Eastern	0.000223	0.000223
South Asian	0.000164	0.000163
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morphology (PubMed:26581903). Has no detectable kinase activity in vitro (PubMed:18556652). {ECO:0000269|PubMed:18556652, ECO:0000269|PubMed:26581903}.
• Disease: DISEASE: Spinocerebellar ataxia, autosomal recessive, 21 (SCAR21) [MIM:616719]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR21 is characterized by cerebellar atrophy and ataxia with onset in early childhood. Patients also manifest recurrent episodes of liver failure, hepatic fibrosis and a peripheral neuropathy. {ECO:0000269|PubMed:26581903}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase (Consensus)

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.678
• rvis_EVS: 0.47
• rvis_percentile_EVS: 78.83

Haploinsufficiency Scores

• pHI: 0.270
• hipred: Y
• hipred_score: 0.637
• ghis: 0.524

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.760

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Scyl1
• Phenotype: muscle phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;peptidyl-tyrosine phosphorylation
• Cellular component: nucleus;cytoplasm;endoplasmic reticulum-Golgi intermediate compartment;Golgi apparatus;cis-Golgi network;microtubule organizing center;cytosol;membrane;COPI vesicle coat
• Molecular function: DNA binding;protein tyrosine kinase activity;ATP binding;cadherin binding