SCYL1

Summary

SCYL1 (SCY1 like pseudokinase 1, HGNC:14372) is a protein-coding gene on chromosome 11q13.1, encoding N-terminal kinase-like protein (Q96KG9). Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum. It is a selective cancer dependency (DepMap: 24.9% of cell lines).

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.

Source: NCBI Gene 57410 — RefSeq curated summary.

At a glance

• Gene–disease (curated): acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (Strong, GenCC)
• GWAS associations: 18
• Clinical variants (ClinVar): 287 total — 19 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 40
• Cancer dependency (DepMap): dependent in 24.9% of screened cell lines
• MANE Select transcript: NM_020680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14372
Approved symbol	SCYL1
Name	SCY1 like pseudokinase 1
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	HT019, P105, GKLP, NKTL, TAPK, TRAP, TEIF, MGC78454
Ensembl gene	ENSG00000142186
Ensembl biotype	protein_coding
OMIM	607982
Entrez	57410

Gene structure

Transcript identifiers

Ensembl transcripts: 54 — 47 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000270176, ENST00000420247, ENST00000524897, ENST00000524944, ENST00000525364, ENST00000526454, ENST00000527009, ENST00000528545, ENST00000529178, ENST00000529981, ENST00000531601, ENST00000532290, ENST00000533862, ENST00000534462, ENST00000872762, ENST00000872763, ENST00000872764, ENST00000872765, ENST00000872766, ENST00000872767, ENST00000872768, ENST00000872769, ENST00000872770, ENST00000872771, ENST00000872772, ENST00000872773, ENST00000872774, ENST00000872775, ENST00000872776, ENST00000872777, ENST00000872778, ENST00000872779, ENST00000872780, ENST00000872781, ENST00000872782, ENST00000872783, ENST00000939455, ENST00000939456, ENST00000939457, ENST00000939458, ENST00000939459, ENST00000939460, ENST00000971861, ENST00000971862, ENST00000971863, ENST00000971864, ENST00000971865, ENST00000971866, ENST00000971867, ENST00000971868, ENST00000971869, ENST00000971870, ENST00000971871, ENST00000971872

RefSeq mRNA: 36 — MANE Select: NM_020680 NM_001048218, NM_001411022, NM_001425179, NM_001425180, NM_001425181, NM_001425182, NM_001425183, NM_001425184, NM_001425185, NM_001425186, NM_001425187, NM_001425188, NM_001425189, NM_001425190, NM_001425191, NM_001425192, NM_001425193, NM_001425194, NM_001425195, NM_001425196, NM_001425197, NM_001425198, NM_001425199, NM_001425200, NM_001425201, NM_001425202, NM_001425203, NM_001425204, NM_001425205, NM_001425206, NM_001425207, NM_001425208, NM_001425209, NM_001425210, NM_001425211, NM_020680

CCDS: CCDS41672, CCDS44646, CCDS91507

Canonical transcript exons

ENST00000270176 — 18 exons

Exon	Start	End
ENSE00001064091	65530629	65530787
ENSE00001119892	65535227	65535382
ENSE00001119896	65532692	65532805
ENSE00001168145	65526783	65526873
ENSE00001168209	65526962	65527117
ENSE00001168239	65525574	65525714
ENSE00003477033	65537809	65537880
ENSE00003479979	65538270	65538324
ENSE00003517868	65537967	65538182
ENSE00003527685	65536259	65536334
ENSE00003561327	65536586	65536750
ENSE00003591490	65525921	65526043
ENSE00003598206	65538442	65538704
ENSE00003615529	65526124	65526350
ENSE00003638225	65535953	65536141
ENSE00003658742	65536986	65537128
ENSE00003715247	65531576	65531683
ENSE00003843086	65525083	65525264

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 96.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.1190 / max 197.1643, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115166	44.5270	1818
115168	0.6473	380
115167	0.5996	350
115169	0.3451	161

Top tissues by expression

258 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	96.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.31	gold quality
left adrenal gland cortex	UBERON:0035825	96.05	gold quality
left adrenal gland	UBERON:0001234	96.04	gold quality
right adrenal gland	UBERON:0001233	96.03	gold quality
gastrocnemius	UBERON:0001388	95.96	gold quality
right lobe of liver	UBERON:0001114	95.92	gold quality
adenohypophysis	UBERON:0002196	95.87	gold quality
right lobe of thyroid gland	UBERON:0001119	95.86	gold quality
right adrenal gland cortex	UBERON:0035827	95.82	gold quality
right ovary	UBERON:0002118	95.74	gold quality
right frontal lobe	UBERON:0002810	95.68	gold quality
stromal cell of endometrium	CL:0002255	95.62	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.57	gold quality
lower esophagus	UBERON:0013473	95.56	gold quality
left lobe of thyroid gland	UBERON:0001120	95.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.49	gold quality
muscle of leg	UBERON:0001383	95.45	gold quality
left uterine tube	UBERON:0001303	95.44	gold quality
right coronary artery	UBERON:0001625	95.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.27	gold quality
left ovary	UBERON:0002119	95.22	gold quality
mucosa of stomach	UBERON:0001199	95.18	gold quality
adrenal cortex	UBERON:0001235	95.18	gold quality
body of stomach	UBERON:0001161	95.07	gold quality
left testis	UBERON:0004533	95.03	gold quality
ascending aorta	UBERON:0001496	95.00	gold quality
prefrontal cortex	UBERON:0000451	94.99	gold quality
thoracic aorta	UBERON:0001515	94.99	gold quality
lower esophagus mucosa	UBERON:0035834	94.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.20
E-MTAB-4850	no	256.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting SCYL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-95-5P	99.89	72.17	3973
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-3920	97.75	69.02	1168
HSA-MIR-8057	97.64	66.54	897
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-6822-3P	96.60	66.06	680
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-7108-5P	96.42	66.17	598
HSA-MIR-6747-5P	96.17	64.99	743

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 24.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 22)

• NTKL is involved in centrosome-related cellular functions (PMID:12036289)
• Molecular cloning of telomerase transcriptional elements-interacting factor,(TEIF). TEIF may take part in the transcriptional activation of hTERT. (PMID:15504359)
• TEIF could specifically activate transcription of beta-pol promoter, but not that of DNA polymerase alpha or delta promoter. The responsible sequences for binding of TEIF were revealed (PMID:15963946)
• TEIF functions as a centrosome regulator. Its participation in DNA damage response, including telomere dysfunction and tumorigenesis. (PMID:19198626)
• TEIF protein and centrosome amplification is commonly found in colorectal tumors. The expression level of TEIF is related to tumor histological grade and malignant degree. (PMID:19958622)
• Scyl1 interacts with 58K/formiminotransferase cyclodeaminase (FTCD) and golgin p115, and is required for the maintenance of Golgi morphology (PMID:20209057)
• Scyl1 participates in the nuclear aminoacylation-dependent tRNA export pathway. (PMID:20505071)
• SCYL1-BP1 can be ubiquitinated and degraded by Pirh2 but not by MDM2, which suggests that SCYL1-BP1 can be regulated by Pirh2. (PMID:20598683)
• suggested that the interaction of SCYL1BP1/Pirh2 could accelerate Pirh2 degradation through an ubiquitin-dependent pathway. SCYL1BP1 may function as an important tumor suppressor gene in HCC development (PMID:22570270)
• TEIF as a novel MSP58-interacting protein. (PMID:24361335)
• Data reveal that Scyl1 is a key organizer of a subset of the COPI machinery. (PMID:24481816)
• TEIF is a downstream effector in EGF/PI3K/Akt signaling. (PMID:24769208)
• Data identified the large GTPase dynamin2 as an interacting protein of NTKL, which might be responsible for the phenotype alterations caused by NTKL overexpression, such as cytokinesis failure, increased cell motility and abnormal of cell division. (PMID:25575811)
• Disruptive SCYL1 mutations underlie a syndrome characterized by recurrent episodes of liver failure, peripheral neuropathy, cerebellar atrophy, and ataxia. (PMID:26581903)
• findings indicate that SCYL1 does not contribute to REST turnover and thus do not support a previous study suggesting a role for SCYL1 in mediating REST degradation (PMID:28570664)
• SCYL1 deficiency can cause recurrent low-GGT cholestatic liver dysfunction in conjunction with a variable neurological phenotype (PMID:29419818)
• SCYL1 splicing mutation causes cerebellar ataxia, recurrent episodes of liver failure, and growth retardation. (PMID:30258122)
• Mutations in NBAS and SCYL1, genetic causes of recurrent liver failure in children: Three case reports and a literature review. (PMID:32146038)
• SCYL1 arginine methylation by PRMT1 is essential for neurite outgrowth via Golgi morphogenesis. (PMID:32583741)
• SCYL1 disease and liver transplantation diagnosed by reanalysis of exome sequencing and deletion/duplication analysis of SCYL1. (PMID:33442927)
• Overexpression of SCYL1 Is Associated with Progression of Breast Cancer. (PMID:36290821)
• SCYL1-mediated regulation of the mTORC1 signaling pathway inhibits autophagy and promotes gastric cancer metastasis. (PMID:39394539)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scyl1	ENSMUSG00000024941
rattus_norvegicus	Scyl1	ENSRNOG00000023668
drosophila_melanogaster	yata	FBGN0260990
caenorhabditis_elegans		WBGENE00012337

Paralogs (2): SCYL3 (ENSG00000000457), SCYL2 (ENSG00000136021)

Protein

Protein identifiers

N-terminal kinase-like protein — Q96KG9 (reviewed: Q96KG9)

Alternative names: Coated vesicle-associated kinase of 90 kDa, SCY1-like protein 1, Telomerase regulation-associated protein, Telomerase transcriptional element-interacting factor, Teratoma-associated tyrosine kinase

All UniProt accessions (6): Q96KG9, E9PK59, E9PPN3, E9PS17, H0YCI6, H0YDH0

UniProt curated annotations — full annotation on UniProt →

Function. Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum. Involved in the maintenance of the Golgi apparatus morphology. Acts as a transcriptional activator. It binds to three different types of GC-rich DNA binding sites (box-A, -B and -C) in the beta-polymerase promoter region. It also binds to the TERT promoter region.

Subunit / interactions. Interacts with GORAB. Interacts with COPA, COPB1 and COPB2. Homooligomer. Interacts with AP2B1.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Endoplasmic reticulum-Golgi intermediate compartment. Golgi apparatus. cis-Golgi network Cytoplasm Cytoplasm Cytoplasm. Centrosome Nucleus.

Tissue specificity. Ubiquitous.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The protein kinase domain is predicted to be catalytically inactive.

Miscellaneous. Non-canonical splice junctions.

Similarity. Belongs to the protein kinase superfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
Q96KG9-1	1	yes
Q96KG9-2	2, Variant 1
Q96KG9-3	3, Variant 2
Q96KG9-4	4
Q96KG9-5	5
Q96KG9-6	6

RefSeq proteins (36): NP_001041683, NP_001397951, NP_001412108, NP_001412109, NP_001412110, NP_001412111, NP_001412112, NP_001412113, NP_001412114, NP_001412115, NP_001412116, NP_001412117, NP_001412118, NP_001412119, NP_001412120, NP_001412121, NP_001412122, NP_001412123, NP_001412124, NP_001412125, NP_001412126, NP_001412127, NP_001412128, NP_001412129, NP_001412130, NP_001412131, NP_001412132, NP_001412133, NP_001412134, NP_001412135, NP_001412136, NP_001412137, NP_001412138, NP_001412139, NP_001412140, NP_065731* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR051177	CIK-Related_Protein	Family

Pfam: PF00069

UniProt features (32 total): compositionally biased region 8, splice variant 6, sequence variant 4, region of interest 4, repeat 3, sequence conflict 3, chain 1, domain 1, modified residue 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KG9-F1	76.40	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 754

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (7): retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), inflammatory response (GO:0006954), intracellular protein localization (GO:0008104), spinal cord motor neuron differentiation (GO:0021522), neuron development (GO:0048666), protein phosphorylation (GO:0006468), vesicle-mediated transport (GO:0016192)

GO Molecular Function (5): DNA binding (GO:0003677), protein kinase activity (GO:0004672), ATP binding (GO:0005524), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), cis-Golgi network (GO:0005801), centrosome (GO:0005813), cytosol (GO:0005829), membrane (GO:0016020), COPI vesicle coat (GO:0030126), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	4
cellular anatomical structure	3
cytoplasm	3
Golgi apparatus	2
Golgi vesicle transport	1
defense response	1
macromolecule localization	1
cell differentiation in spinal cord	1
ventral spinal cord development	1
central nervous system neuron differentiation	1
neuron differentiation	1
cell development	1
phosphorylation	1
protein modification process	1
transport	1
cellular process	1
nucleic acid binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cell adhesion molecule binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
centriole	1
microtubule organizing center	1
vesicle coat	1
COPI-coated vesicle membrane	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1026 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCYL1	GORAB	Q5T7V8	984
SCYL1	RCHY1	Q96PM5	891
SCYL1	COPG2	Q9UBF2	664
SCYL1	RAB6A	P20340	554
SCYL1	LCTL	Q6UWM7	498
SCYL1	COIL	P38432	463
SCYL1	XPOT	O43592	449
SCYL1	SCYL2	Q6P3W7	441
SCYL1	ATXN1	P54253	439
SCYL1	SMN1	Q16637	430
SCYL1	FAM222A	Q5U5X8	424
SCYL1	SLC22A4	Q9H015	419
SCYL1	ITGB3BP	Q13352	418
SCYL1	TAFAZZIN	Q16635	416
SCYL1	SNRPG	P62308	383

IntAct

72 interactions, top by confidence:

A	B	Type	Score
SEC31A	SEC13	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SCYL1	SEC31A	psi-mi:“MI:0914”(association)	0.710
SCYL1	SEC31A	psi-mi:“MI:0915”(physical association)	0.710
ZMYND19	TNFAIP1	psi-mi:“MI:0914”(association)	0.670
AURKA	WDR62	psi-mi:“MI:0914”(association)	0.530
SEC31A	NOP14	psi-mi:“MI:0914”(association)	0.530
NEK7	P4HA2	psi-mi:“MI:0914”(association)	0.510
SCYL1	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
SCYL1	EBNA-LP	psi-mi:“MI:0915”(physical association)	0.370
SCYL1	E2	psi-mi:“MI:0915”(physical association)	0.370
CDC25A	SCYL1	psi-mi:“MI:0915”(physical association)	0.370
SCYL1	CHD1L	psi-mi:“MI:0915”(physical association)	0.370
GORAB	SCYL1	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
KSR1		psi-mi:“MI:0914”(association)	0.350
MAPKAPK3	HERC2	psi-mi:“MI:0914”(association)	0.350
SCYL1	CNOT1	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
COPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
COPB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
COPE	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (236): SEC31A (Affinity Capture-MS), SCYL1 (Affinity Capture-MS), SCYL1 (Affinity Capture-Western), SCYL1 (Co-fractionation), SCYL1 (Co-fractionation), SCYL1 (Affinity Capture-MS), SCYL1 (Proximity Label-MS), SCYL1 (Affinity Capture-MS), SCYL1 (Affinity Capture-MS), SCYL1 (Affinity Capture-MS), SCYL1 (Affinity Capture-MS), CCNF (Two-hybrid), CCNF (Affinity Capture-Western), CCNF (Reconstituted Complex), SCYL1 (Biochemical Activity)

ESM2 similar proteins: A1A4I4, A4K436, A6QLH6, D3ZVM4, F1M5F3, F1N2W9, O00459, O08908, O43272, O60336, O95294, P0C928, P23726, P70268, Q0VGM9, Q16512, Q1JQD7, Q1PSW8, Q3KRC5, Q496Y0, Q5M9F8, Q5R812, Q5RE34, Q5RJZ1, Q5RKZ7, Q5XIS9, Q5ZIW1, Q63433, Q63788, Q6H1L8, Q6NS57, Q6NYU2, Q6PFQ7, Q8BZ03, Q8R1T1, Q91XI1, Q920N2, Q92889, Q92994, Q96G46

Diamond homologs: A6QLH6, Q28FH2, Q55GS2, Q561M0, Q5M9F8, Q96KG9, Q9EQC5, G4N7X0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AKT1	“up-regulates activity”	SCYL1	phosphorylation
SCYL1	“down-regulates activity”	CEP250	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
COPI-mediated anterograde transport	7	17.1×	6e-05
COPI-dependent Golgi-to-ER retrograde traffic	6	14.8×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
intra-Golgi vesicle-mediated transport	5	46.2×	3e-05
endoplasmic reticulum to Golgi vesicle-mediated transport	5	11.9×	4e-03
intracellular protein transport	7	8.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

287 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	9
Uncertain significance	133
Likely benign	73
Benign	11

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1028665	NM_020680.4(SCYL1):c.451C>T (p.Arg151Ter)	Pathogenic
218907	NM_020680.4(SCYL1):c.937del (p.Val313fs)	Pathogenic
218908	NM_020680.4(SCYL1):c.1509_1510del (p.Ala504fs)	Pathogenic
218910	NM_020680.4(SCYL1):c.1636C>T (p.Gln546Ter)	Pathogenic
2405187	NM_020680.4(SCYL1):c.560del (p.Pro187fs)	Pathogenic
2444060	NM_020680.4(SCYL1):c.1386+1G>A	Pathogenic
3255054	NM_020680.4(SCYL1):c.1180del (p.Val394fs)	Pathogenic
3375224	NM_020680.4(SCYL1):c.1173_1174dup (p.His392fs)	Pathogenic
3640969	NM_020680.4(SCYL1):c.2094dup (p.Glu699Ter)	Pathogenic
446290	NM_020680.4(SCYL1):c.1882C>T (p.Gln628Ter)	Pathogenic
446291	NM_020680.4(SCYL1):c.1433A>G (p.Asp478Gly)	Pathogenic
446292	NM_020680.4(SCYL1):c.256G>T (p.Glu86Ter)	Pathogenic
446293	NM_020680.4(SCYL1):c.169C>T (p.Gln57Ter)	Pathogenic
446294	NM_020680.4(SCYL1):c.314C>T (p.Ala105Val)	Pathogenic
4761686	NM_020680.4(SCYL1):c.1021del (p.Phe340_Leu341insTer)	Pathogenic
521096	NM_020680.4(SCYL1):c.2066_2067del (p.Pro689fs)	Pathogenic
691875	NM_020680.4(SCYL1):c.1534dup (p.Cys512fs)	Pathogenic
985074	NM_020680.4(SCYL1):c.1039C>T (p.Gln347Ter)	Pathogenic
985715	NM_020680.4(SCYL1):c.1346_1347del (p.Thr449fs)	Pathogenic
2181462	NM_020680.4(SCYL1):c.2031+1G>C	Likely pathogenic
218909	NM_020680.4(SCYL1):c.1230+1G>A	Likely pathogenic
2444353	NM_020680.4(SCYL1):c.1591_1610del (p.Arg531fs)	Likely pathogenic
2819156	NM_020680.4(SCYL1):c.1117-1G>A	Likely pathogenic
3341292	NM_020680.4(SCYL1):c.143_144del (p.Val47_Tyr48insTer)	Likely pathogenic
3381067	NM_020680.4(SCYL1):c.1841_1842del (p.Pro614fs)	Likely pathogenic
3391234	NM_020680.4(SCYL1):c.476del (p.Gly159fs)	Likely pathogenic
3709105	NM_020680.4(SCYL1):c.459C>T (p.Gly153=)	Likely pathogenic
548462	NM_020680.4(SCYL1):c.1412C>T (p.Ala471Val)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

5289 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65526136:T:C	F130L	1.000
11:65526138:C:A	F130L	1.000
11:65526138:C:G	F130L	1.000
11:65526211:T:A	W155R	1.000
11:65526211:T:C	W155R	1.000
11:65530729:T:C	L317P	1.000
11:65531673:T:C	L369P	1.000
11:65531676:T:C	L370P	1.000
11:65532729:T:A	V385D	1.000
11:65532761:G:C	G396R	1.000
11:65532762:G:A	G396D	1.000
11:65532801:T:A	V409D	1.000
11:65535279:T:C	L428P	1.000
11:65535327:T:A	I444N	1.000
11:65535337:C:A	N447K	1.000
11:65535337:C:G	N447K	1.000
11:65535345:T:A	V450D	1.000
11:65535347:T:C	C451R	1.000
11:65535349:C:G	C451W	1.000
11:65535351:T:C	L452P	1.000
11:65536004:T:C	F480L	1.000
11:65536006:T:A	F480L	1.000
11:65536006:T:G	F480L	1.000
11:65536026:G:A	G487D	1.000
11:65536034:G:C	G490R	1.000
11:65536035:G:A	G490D	1.000
11:65536652:C:A	A573D	1.000
11:65527019:C:A	R251S	0.999
11:65530669:T:C	L297P	0.999
11:65530720:T:C	L314P	0.999

dbSNP variants (sampled 300 via entrez): RS1000035825 (11:65531340 G>A,C), RS1000061551 (11:65534015 G>T), RS1000535755 (11:65538682 G>A), RS1000639960 (11:65532529 C>G,T), RS1000724550 (11:65532250 C>A), RS1001339116 (11:65528764 A>G), RS1001524743 (11:65534209 C>T), RS1001743971 (11:65534063 C>G), RS1001858477 (11:65533192 C>T), RS1001923572 (11:65533209 G>A), RS1002061021 (11:65527197 T>C), RS1002115439 (11:65527672 C>A,T), RS1002521155 (11:65535713 G>A,T), RS1002640248 (11:65529790 A>G), RS1002750144 (11:65535549 G>A)

Disease associations

OMIM: gene MIM:607982 | disease phenotypes: MIM:616719, MIM:601216

GenCC curated gene-disease

Disease	Classification	Inheritance
acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome	Strong	Autosomal recessive

Mondo (2): acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (MONDO:0014744), brachyolmia-amelogenesis imperfecta syndrome (MONDO:0011018)

Orphanet (2): Acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (Orphanet:466794), Brachyolmia-amelogenesis imperfecta syndrome (Orphanet:2899)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000641	Dysmetric saccades
HP:0000648	Optic atrophy
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001395	Hepatic fibrosis
HP:0001399	Hepatic failure
HP:0001433	Hepatosplenomegaly
HP:0001744	Splenomegaly
HP:0001762	Talipes equinovarus
HP:0001945	Fever
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002073	Progressive cerebellar ataxia
HP:0002080	Intention tremor
HP:0002240	Hepatomegaly
HP:0002359	Frequent falls
HP:0002460	Distal muscle weakness
HP:0002936	Distal sensory impairment
HP:0003202	Skeletal muscle atrophy
HP:0003401	Paresthesia
HP:0003474	Somatic sensory dysfunction
HP:0003593	Infantile onset
HP:0006554	Acute hepatic failure

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000700_6	Vertical cup-disc ratio	4.000000e-09
GCST002481_8	Acne (severe)	3.000000e-11
GCST007691_28	Femoral neck bone mineral density	4.000000e-06
GCST010002_240	Refractive error	3.000000e-11
GCST010796_2230	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-12
GCST010796_2231	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-12
GCST010796_2232	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-12
GCST010796_2233	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-12
GCST010796_2234	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-11
GCST010796_2235	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-12
GCST010796_2236	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-11
GCST010796_2237	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-10
GCST010796_2238	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-10
GCST010796_2239	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10
GCST010796_2240	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_2241	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09
GCST010796_2242	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST90020026_506	Hip index	5.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007785	femoral neck bone mineral density
EFO:0004327	electrocardiography
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — SCY1 family

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	4
Valproic Acid	affects cotreatment, decreases expression, increases methylation	3
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Arsenic	decreases expression, increases abundance, increases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Cytarabine	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Dinitrochlorobenzene	affects binding	1

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 1 transformed cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3GI	Abcam HEK293T SCYL1 KO	Transformed cell line	Female
CVCL_TK18	HAP1 SCYL1 (-) 1	Cancer cell line	Male
CVCL_TK19	HAP1 SCYL1 (-) 2	Cancer cell line	Male
CVCL_WG65	DHMCi005-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.