SCYL2

Summary

SCYL2 (SCY1 like pseudokinase 2, HGNC:19286) is a protein-coding gene on chromosome 12q23.1, encoding SCY1-like protein 2 (Q6P3W7). Component of the AP2-containing clathrin coat that may regulate clathrin-dependent trafficking at plasma membrane, TGN and endosomal system.

The protein encoded by this gene associates with clathrin-coated complexes at the plasma membrane and with endocytic coated vesicles. The encoded protein phosphorylates the beta2 subunit of the plasma membrane adapter complex AP2 and interacts with clathrin, showing involvement in clathrin-dependent pathways between the trans-Golgi network and the endosomal system. In addition, this protein has a role in the Wnt signaling pathway by targeting frizzled 5 (Fzd5) for lysosomal degradation. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 55681 — RefSeq curated summary.

At a glance

• Gene–disease (curated): arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 157 total — 4 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 56
• MANE Select transcript: NM_017988

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19286
Approved symbol	SCYL2
Name	SCY1 like pseudokinase 2
Location	12q23.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1360, CVAK104
Ensembl gene	ENSG00000136021
Ensembl biotype	protein_coding
OMIM	616365
Entrez	55681

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 13 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000360820, ENST00000547202, ENST00000547735, ENST00000548392, ENST00000548871, ENST00000549486, ENST00000549687, ENST00000550067, ENST00000550251, ENST00000553148, ENST00000635101, ENST00000872993, ENST00000872994, ENST00000872995, ENST00000872996, ENST00000872997, ENST00000872998, ENST00000930682, ENST00000930683, ENST00000951396

RefSeq mRNA: 5 — MANE Select: NM_017988 NM_001317784, NM_001330253, NM_001330254, NM_001330256, NM_017988

CCDS: CCDS81726, CCDS9076

Canonical transcript exons

ENST00000360820 — 18 exons

Exon	Start	End
ENSE00000922749	100315558	100315734
ENSE00000922752	100317803	100317925
ENSE00000922758	100334166	100334266
ENSE00001293557	100326622	100326754
ENSE00001361834	100314489	100314614
ENSE00001361837	100313422	100313538
ENSE00001361852	100312432	100312653
ENSE00001402641	100338528	100341715
ENSE00001428713	100267177	100267792
ENSE00003467015	100335811	100335906
ENSE00003482329	100335625	100335691
ENSE00003484330	100337387	100337506
ENSE00003491005	100282943	100283147
ENSE00003500128	100323525	100323638
ENSE00003511250	100329201	100329319
ENSE00003611836	100298031	100298175
ENSE00003640873	100311044	100311193
ENSE00003642112	100291503	100291660

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 96.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.3433 / max 335.0840, expressed in 1818 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127567	15.8212	1806
127563	8.5360	1659
127564	5.4672	1578
127565	2.2499	1298
127562	2.1411	963
127566	0.8301	569
127568	0.2978	106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	96.18	gold quality
corpus epididymis	UBERON:0004359	96.13	gold quality
secondary oocyte	CL:0000655	95.77	gold quality
jejunal mucosa	UBERON:0000399	95.69	gold quality
colonic mucosa	UBERON:0000317	95.56	gold quality
esophagus squamous epithelium	UBERON:0006920	95.55	gold quality
palpebral conjunctiva	UBERON:0001812	94.16	gold quality
adrenal tissue	UBERON:0018303	93.92	gold quality
amniotic fluid	UBERON:0000173	93.55	gold quality
cortical plate	UBERON:0005343	93.55	gold quality
oral cavity	UBERON:0000167	93.05	gold quality
rectum	UBERON:0001052	93.03	gold quality
cauda epididymis	UBERON:0004360	91.59	gold quality
monocyte	CL:0000576	91.58	gold quality
oocyte	CL:0000023	91.56	gold quality
jejunum	UBERON:0002115	91.51	gold quality
endothelial cell	CL:0000115	91.32	gold quality
ganglionic eminence	UBERON:0004023	91.28	gold quality
mononuclear cell	CL:0000842	91.20	gold quality
caput epididymis	UBERON:0004358	91.09	gold quality
epithelium of nasopharynx	UBERON:0001951	91.06	gold quality
sperm	CL:0000019	91.02	gold quality
calcaneal tendon	UBERON:0003701	91.01	gold quality
leukocyte	CL:0000738	90.92	gold quality
colonic epithelium	UBERON:0000397	90.71	gold quality
trabecular bone tissue	UBERON:0002483	90.67	gold quality
upper leg skin	UBERON:0004262	89.97	gold quality
lower lobe of lung	UBERON:0008949	89.81	gold quality
tonsil	UBERON:0002372	89.66	gold quality
islet of Langerhans	UBERON:0000006	89.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting SCYL2, 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-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AT-5P	99.96	70.83	2666

Literature-anchored findings (GeneRIF, showing 6)

• CVAK104 binds ATP and functions in vitro as a poly-L-lysine-stimulated kinase that is capable of autophosphorylation and phosphorylating the beta2-adaptin subunit of AP2. (PMID:15809293)
• Together, our data suggest a function for CVAK104 in clathrin-dependent pathways between the trans-Golgi network and the endosomal system. (PMID:16914521)
• CVAK104 is an evolutionarily conserved protein involved in SNARE sorting that is essential for normal embryonic development (PMID:17587408)
• Studies identify CVAK104 as a novel binding partner of Dishevelled (Dvl) and that CVAK104 also interacts with Fzd5. (PMID:19643732)
• results suggest that SCYL2 serves as a regulatory factor for Vpu, reducing the extent of Vpu phosphorylation and consequently enhancing BST2-mediated viral restriction. (PMID:23047923)
• results suggest that severe neurogenic arthrogryposis with brain malformation is the human phenotypic consequence of SCYL2 loss of function mutations. (PMID:31960134)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	scyl2	ENSDARG00000032627
mus_musculus	Scyl2	ENSMUSG00000069539
rattus_norvegicus	Scyl2	ENSRNOG00000024955
drosophila_melanogaster	CG1951	FBGN0039623
caenorhabditis_elegans	ZC581.9	WBGENE00022635

Paralogs (2): SCYL3 (ENSG00000000457), SCYL1 (ENSG00000142186)

Protein

Protein identifiers

SCY1-like protein 2 — Q6P3W7 (reviewed: Q6P3W7)

Alternative names: Coated vesicle-associated kinase of 104 kDa

All UniProt accessions (6): A0A0U1RQQ9, Q6P3W7, F8VPW3, F8VSC5, H0YI32, H0YIK6

UniProt curated annotations — full annotation on UniProt →

Function. Component of the AP2-containing clathrin coat that may regulate clathrin-dependent trafficking at plasma membrane, TGN and endosomal system. A possible serine/threonine-protein kinase toward the beta2-subunit of the plasma membrane adapter complex AP2 and other proteins in presence of poly-L-lysine has not been confirmed. By regulating the expression of excitatory receptors at synapses, plays an essential role in neuronal function and signaling and in brain development.

Subunit / interactions. Interacts with clathrin and AP2B1; the interaction mediates the association with the AP-2 complex.

Subcellular location. Cytoplasmic vesicle. Clathrin-coated vesicle. Golgi apparatus. trans-Golgi network membrane. Endosome membrane.

Post-translational modifications. Could autophosphorylate in presence of poly-L-lysine.

Disease relevance. Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum (AMC4) [MIM:618766] A form of arthrogryposis multiplex congenita, a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. AMC4 is an autosomal recessive, severe form with onset in utero. Patients manifest little or no fetal movements, significant contractures affecting the upper and lower limbs, dysmorphic facial features, optic atrophy, limb fractures, profound global developmental delay, seizures, and peripheral neuropathy. Many patients die in early childhood. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily.

RefSeq proteins (5): NP_001304713, NP_001317182, NP_001317183, NP_001317185, NP_060458* (*=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 (24 total): sequence conflict 8, sequence variant 4, region of interest 3, compositionally biased region 3, modified residue 2, chain 1, domain 1, repeat 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P3W7-F1	71.63	0.39

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 (2): 677, 708

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 302 (showing top): GOBP_FOREBRAIN_NEURON_DEVELOPMENT, MODULE_97, ELVIDGE_HYPOXIA_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_LYSOSOMAL_TRANSPORT, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_VACUOLAR_TRANSPORT, MODULE_182, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_FOREBRAIN_DEVELOPMENT, CEBPB_01, GOBP_FOREBRAIN_GENERATION_OF_NEURONS, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY

GO Biological Process (7): brain development (GO:0007420), endosome to lysosome transport (GO:0008333), pyramidal neuron development (GO:0021860), receptor internalization (GO:0031623), clathrin-dependent endocytosis (GO:0072583), negative regulation of canonical Wnt signaling pathway (GO:0090090), protein phosphorylation (GO:0006468)

GO Molecular Function (4): protein kinase activity (GO:0004672), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), protein binding (GO:0005515)

GO Cellular Component (6): Golgi apparatus (GO:0005794), endosome membrane (GO:0010008), clathrin-coated vesicle (GO:0030136), endosome (GO:0005768), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
receptor-mediated endocytosis	2
cytoplasm	2
endomembrane system	2
central nervous system development	1
animal organ development	1
head development	1
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
pyramidal neuron differentiation	1
forebrain neuron development	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
phosphorylation	1
protein modification process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
binding	1
intracellular membrane-bounded organelle	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
coated vesicle	1
cytoplasmic vesicle	1
cellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

788 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCYL2	CLINT1	Q14677	443
SCYL2	SCYL1	Q96KG9	441
SCYL2	SCYL3	Q8IZE3	438
SCYL2	STX8	Q9UNK0	393
SCYL2	AP1M1	Q9BXS5	381
SCYL2	GAK	O14976	376
SCYL2	VTI1B	Q9UEU0	374
SCYL2	AFTPH	Q6ULP2	371
SCYL2	HEATR5B	Q9P2D3	367
SCYL2	PHIP	Q8WWQ0	360
SCYL2	CDK16	Q00536	357
SCYL2	AP2B1	P21851	348
SCYL2	MTCL2	O94964	345
SCYL2	N4BP2	Q86UW6	343
SCYL2	CSRNP3	Q8WYN3	341

IntAct

94 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SCYL2	DVL1	psi-mi:“MI:0915”(physical association)	0.540
DVL1	SCYL2	psi-mi:“MI:0915”(physical association)	0.540
DVL1	SCYL2	psi-mi:“MI:0407”(direct interaction)	0.540
SCYL2	FZD5	psi-mi:“MI:0915”(physical association)	0.540
FZD5	SCYL2	psi-mi:“MI:0407”(direct interaction)	0.540
CRK	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	SEC16A	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
Dlg4	SCYL2	psi-mi:“MI:0407”(direct interaction)	0.440
SCYL2	ACTC1	psi-mi:“MI:0915”(physical association)	0.400
ZFYVE9	SCYL2	psi-mi:“MI:0915”(physical association)	0.370
SCYL2	CLTC	psi-mi:“MI:0914”(association)	0.350
GTSE1	HIP1	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
ARRB1		psi-mi:“MI:0914”(association)	0.350
ARRB2		psi-mi:“MI:0914”(association)	0.350
CDK1	RBMXL2	psi-mi:“MI:0914”(association)	0.350
COQ2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
COX15	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SOAT1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
VDAC1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SPATA1	ANKHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (202): SCYL2 (Affinity Capture-MS), CLTC (Affinity Capture-MS), ALYREF (Affinity Capture-MS), PCBP2 (Co-fractionation), PCMT1 (Co-fractionation), SCYL2 (Co-fractionation), SCYL2 (Co-fractionation), SCYL2 (Co-fractionation), SCYL2 (Co-fractionation), SCYL2 (Co-fractionation), SCYL2 (Affinity Capture-MS), SCYL2 (Proximity Label-MS), SCYL2 (Proximity Label-MS), SCYL2 (Proximity Label-MS), SCYL2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C0TYJ0, A0A8I5ZNK2, A1L1C7, D3ZSZ3, E1BMN8, E2QWQ2, O42099, O43242, O54949, O55047, O70133, O88506, O95747, P19139, P21868, P28020, P33674, P34947, P49137, P49336, P68399, P68400, Q08CW1, Q15139, Q17IE8, Q1ECX4, Q2KJ46, Q58A45, Q5R495, Q60737, Q640Q5, Q66KH9, Q68FK8, Q6P3N6, Q6P3W7, Q6P9R2, Q863I2, Q8BWD8, Q8C0V0, Q8CFE4

Diamond homologs: F4I313, Q4R8T9, Q6P3W7, Q8CFE4, Q8IVW4, Q8SRF5, Q8W490, Q9C9H8, Q55BQ3, Q5JLS2, Q5QNM6, Q9SN43, O01798, P38070, Q96QS6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 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
Lysosome Vesicle Biogenesis	6	26.1×	2e-05
Golgi Associated Vesicle Biogenesis	5	13.4×	3e-03
Cargo recognition for clathrin-mediated endocytosis	9	12.6×	1e-05
Clathrin-mediated endocytosis	11	12.5×	6e-07
Regulation of HSF1-mediated heat shock response	5	9.3×	9e-03
RAF/MAP kinase cascade	8	6.5×	3e-03
Ub-specific processing proteases	8	5.7×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of protein ubiquitination	5	15.5×	5e-03
axonogenesis	6	10.5×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	5
Uncertain significance	114
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
2288887	NM_017988.6(SCYL2):c.298C>T (p.Arg100Ter)	Pathogenic
2445467	NM_017988.6(SCYL2):c.214_234del (p.Asp72_Glu78del)	Pathogenic
810843	NM_017988.6(SCYL2):c.106C>T (p.Arg36Ter)	Pathogenic
810844	NM_017988.6(SCYL2):c.1624dup (p.Val542fs)	Pathogenic
1308643	NM_017988.6(SCYL2):c.97del (p.Asp33fs)	Likely pathogenic
1308644	NM_017988.6(SCYL2):c.176dup (p.Glu60fs)	Likely pathogenic
2671711	NM_017988.6(SCYL2):c.598dup (p.Cys200fs)	Likely pathogenic
4077488	NM_017988.6(SCYL2):c.1215T>A (p.Tyr405Ter)	Likely pathogenic
4292525	NM_017988.6(SCYL2):c.2330del (p.Met777fs)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

6182 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:100283005:T:A	V12D	1.000
12:100283043:G:A	G25R	1.000
12:100283043:G:C	G25R	1.000
12:100283044:G:A	G25E	1.000
12:100283048:T:A	N26K	1.000
12:100283048:T:G	N26K	1.000
12:100283053:T:A	V28D	1.000
12:100283059:G:T	R30I	1.000
12:100283064:T:C	F32L	1.000
12:100283065:T:C	F32S	1.000
12:100283066:T:A	F32L	1.000
12:100283066:T:G	F32L	1.000
12:100283109:T:A	W47R	1.000
12:100283109:T:C	W47R	1.000
12:100283124:G:C	G52R	1.000
12:100283125:G:A	G52D	1.000
12:100283130:A:G	K54E	1.000
12:100283131:A:T	K54I	1.000
12:100283132:A:C	K54N	1.000
12:100283132:A:T	K54N	1.000
12:100291509:G:C	A62P	1.000
12:100291513:T:A	V63D	1.000
12:100291609:G:C	R95P	1.000
12:100291618:A:G	H98R	1.000
12:100291630:T:A	L102H	1.000
12:100291636:T:A	V104D	1.000
12:100291660:G:T	R112M	1.000
12:100298042:C:A	A116E	1.000
12:100298047:T:C	C118R	1.000
12:100298048:G:A	C118Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000002371 (12:100332102 A>G), RS1000015151 (12:100297739 C>A,G), RS1000070133 (12:100266201 C>T), RS1000137175 (12:100304068 C>T), RS1000232571 (12:100295158 C>T), RS1000233480 (12:100325236 C>A), RS1000250468 (12:100282881 A>G), RS1000265093 (12:100295410 T>G), RS1000396706 (12:100328749 A>T), RS1000448328 (12:100270297 A>G), RS1000473708 (12:100277004 T>C), RS1000479668 (12:100289245 T>C), RS1000505101 (12:100321337 C>A), RS1000535850 (12:100307280 T>A,G), RS1000536727 (12:100314277 C>T)

Disease associations

OMIM: gene MIM:616365 | disease phenotypes: MIM:618766

GenCC curated gene-disease

Disease	Classification	Inheritance
arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum	Strong	Autosomal recessive

Mondo (1): arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum (MONDO:0032903)

Orphanet (0):

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000160	Narrow mouth
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000414	Bulbous nose
HP:0000470	Short neck
HP:0000648	Optic atrophy
HP:0001188	Hand clenching
HP:0001239	Wrist flexion contracture
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001284	Areflexia
HP:0001357	Plagiocephaly
HP:0001371	Flexion contracture
HP:0001522	Death in infancy
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001562	Oligohydramnios
HP:0001623	Breech presentation
HP:0001627	Abnormal heart morphology
HP:0001838	Rocker bottom foot
HP:0002058	Myopathic facies
HP:0002098	Respiratory distress
HP:0002380	Fasciculations

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001827_1	Squamous cell carcinoma	1.000000e-10
GCST012490_592	Femur bone mineral density x serum urate levels interaction	1.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Tobacco Smoke Pollution	increases expression, increases methylation	3
trichostatin A	decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
Temozolomide	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, increases expression	1
Endosulfan	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2EV	Abcam HeLa SCYL2 KO	Cancer cell line	Female
CVCL_TK20	HAP1 SCYL2 (-) 1	Cancer cell line	Male
CVCL_TK21	HAP1 SCYL2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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