SCYL3

Summary

SCYL3 (SCY1 like pseudokinase 3, HGNC:19285) is a protein-coding gene on chromosome 1q24.2, encoding Protein-associating with the carboxyl-terminal domain of ezrin (Q8IZE3). May play a role in regulating cell adhesion/migration complexes in migrating cells.

This gene encodes a protein with a kinase domain and four HEAT repeats. The encoded protein interacts with the C-terminal domain of ezrin, an ERM protein, and may play a role in cell adhesion and migration. Alternative splicing results in multiple transcript variants encoding multiple isoforms.

Source: NCBI Gene 57147 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 103 total
• MANE Select transcript: NM_020423

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19285
Approved symbol	SCYL3
Name	SCY1 like pseudokinase 3
Location	1q24.2
Locus type	gene with protein product
Status	Approved
Aliases	PACE-1, PACE1
Ensembl gene	ENSG00000000457
Ensembl biotype	protein_coding
OMIM	608192
Entrez	57147

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000367770, ENST00000367771, ENST00000367772, ENST00000423670, ENST00000470238, ENST00000910083, ENST00000910084, ENST00000910085, ENST00000910086, ENST00000910087, ENST00000910088, ENST00000937694, ENST00000966135

RefSeq mRNA: 2 — MANE Select: NM_020423 NM_020423, NM_181093

CCDS: CCDS1286, CCDS1287

Canonical transcript exons

ENST00000367771 — 13 exons

Exon	Start	End
ENSE00000789668	169854270	169854964
ENSE00000814448	169868928	169869039
ENSE00000814452	169859041	169859212
ENSE00003505435	169875978	169876091
ENSE00003557980	169862613	169862797
ENSE00003589316	169878634	169878819
ENSE00003592502	169870255	169870357
ENSE00003617092	169864369	169864508
ENSE00003631661	169873696	169873752
ENSE00003656990	169888676	169888890
ENSE00003694021	169866896	169866973
ENSE00003704126	169849631	169853772
ENSE00003849588	169893788	169893896

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 96.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1072 / max 62.0517, expressed in 1775 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15867	8.3835	1764
15866	0.4197	198
15865	0.3040	162

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.94	gold quality
secondary oocyte	CL:0000655	92.99	gold quality
oocyte	CL:0000023	88.84	gold quality
amniotic fluid	UBERON:0000173	86.97	gold quality
pancreatic ductal cell	CL:0002079	86.79	gold quality
epithelium of nasopharynx	UBERON:0001951	86.76	gold quality
palpebral conjunctiva	UBERON:0001812	84.58	gold quality
esophagus squamous epithelium	UBERON:0006920	83.60	gold quality
choroid plexus epithelium	UBERON:0003911	83.37	gold quality
calcaneal tendon	UBERON:0003701	83.09	gold quality
endothelial cell	CL:0000115	83.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.67	gold quality
rectum	UBERON:0001052	82.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.14	gold quality
jejunal mucosa	UBERON:0000399	81.46	gold quality
squamous epithelium	UBERON:0006914	81.19	gold quality
tendon	UBERON:0000043	80.89	gold quality
blood	UBERON:0000178	80.84	gold quality
gastrocnemius	UBERON:0001388	80.54	gold quality
gingival epithelium	UBERON:0001949	80.51	gold quality
gall bladder	UBERON:0002110	80.40	gold quality
duodenum	UBERON:0002114	80.40	gold quality
right lobe of liver	UBERON:0001114	80.37	gold quality
epithelial cell of pancreas	CL:0000083	80.31	silver quality
tonsil	UBERON:0002372	80.26	gold quality
tibia	UBERON:0000979	80.16	gold quality
muscle of leg	UBERON:0001383	80.11	gold quality
ventricular zone	UBERON:0003053	79.99	gold quality
bronchial epithelial cell	CL:0002328	79.98	gold quality
minor salivary gland	UBERON:0001830	79.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	132.39
E-ANND-3	yes	4.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting SCYL3, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-491-5P	99.13	65.98	1468

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	scyl3	ENSDARG00000027046
mus_musculus	Scyl3	ENSMUSG00000026584
rattus_norvegicus	Scyl3	ENSRNOG00000025318
drosophila_melanogaster	CG1344	FBGN0027507

Paralogs (2): SCYL2 (ENSG00000136021), SCYL1 (ENSG00000142186)

Protein

Protein identifiers

Protein-associating with the carboxyl-terminal domain of ezrin — Q8IZE3 (reviewed: Q8IZE3)

Alternative names: Ezrin-binding protein PACE-1, SCY1-like protein 3

All UniProt accessions (2): Q8IZE3, X6RHX1

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in regulating cell adhesion/migration complexes in migrating cells.

Subunit / interactions. Interacts with EZR/VIL2 C-terminal domain.

Subcellular location. Cytoplasm. Golgi apparatus. Cell projection. Lamellipodium.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. May be myristoylated; myristoylation may target it to Golgi compartment. Phosphorylated.

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

Similarity. Belongs to the protein kinase superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IZE3-1	1	yes
Q8IZE3-2	2

RefSeq proteins (2): NP_065156, NP_851607 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR021133	HEAT_type_2	Repeat
IPR051177	CIK-Related_Protein	Family

Pfam: PF07714

UniProt features (21 total): region of interest 5, repeat 4, modified residue 2, sequence variant 2, initiator methionine 1, chain 1, compositionally biased region 1, lipid moiety-binding region 1, splice variant 1, mutagenesis site 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZE3-F1	69.60	0.50

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 (3): 439, 707, 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
2–6	no golgi targeting, accumulates in the cytoplasm.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 156 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, ATACCTC_MIR202, GOBP_NEUROGENESIS, YY1_Q6, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD, GOBP_SPINAL_CORD_MOTOR_NEURON_DIFFERENTIATION, GOBP_VENTRAL_SPINAL_CORD_DEVELOPMENT, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, ETF_Q6, GCCATNTTG_YY1_Q6, MODULE_104, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP

GO Biological Process (6): inflammatory response (GO:0006954), intracellular protein localization (GO:0008104), cell migration (GO:0016477), spinal cord motor neuron differentiation (GO:0021522), neuron development (GO:0048666), protein phosphorylation (GO:0006468)

GO Molecular Function (4): ATP binding (GO:0005524), identical protein binding (GO:0042802), protein kinase activity (GO:0004672), protein binding (GO:0005515)

GO Cellular Component (7): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), lamellipodium (GO:0030027), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
endomembrane system	2
intracellular membrane-bounded organelle	2
defense response	1
macromolecule localization	1
cell motility	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
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
intracellular anatomical structure	1
cell leading edge	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCYL3	EZR	P15311	812
SCYL3	SCYL2	Q6P3W7	438
SCYL3	XPOT	O43592	381
SCYL3	PLEKHA6	Q9Y2H5	365
SCYL3	NIM1K	Q8IY84	336
SCYL3	GOPC	Q9HD26	292
SCYL3	FAM222A	Q5U5X8	285
SCYL3	MTF1	Q14872	250
SCYL3	ASCC3	Q8N3C0	249
SCYL3	PRKAG1	P54619	243
SCYL3	NTRK1	P04629	241
SCYL3	PRKAB2	O43741	234
SCYL3	MSRB2	Q9Y3D2	222
SCYL3	UBR1	Q8IWV7	221
SCYL3	ROS1	P08922	216

IntAct

44 interactions, top by confidence:

A	B	Type	Score
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
SCYL3	TXN2	psi-mi:“MI:0915”(physical association)	0.670
TXN2	SCYL3	psi-mi:“MI:0915”(physical association)	0.670
SCYL3	EZR	psi-mi:“MI:0915”(physical association)	0.610
EZR	SCYL3	psi-mi:“MI:0915”(physical association)	0.610
LHX8	SCYL3	psi-mi:“MI:0915”(physical association)	0.560
SCYL3	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.560
SCYL3	EZR	psi-mi:“MI:0915”(physical association)	0.400
SCYL3	ITGB1	psi-mi:“MI:0915”(physical association)	0.400
SCYL3	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
SCYL3	PPIH	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
COPG1	ATL3	psi-mi:“MI:0914”(association)	0.350
COPG2	ILVBL	psi-mi:“MI:0914”(association)	0.350
COPZ1	ATL3	psi-mi:“MI:0914”(association)	0.350
SYAP1	GPR107	psi-mi:“MI:0914”(association)	0.350
MRPS17	POLRMT	psi-mi:“MI:0914”(association)	0.350
SCYL3	AURKA	psi-mi:“MI:0914”(association)	0.350
SCYL3	CHEK1	psi-mi:“MI:0914”(association)	0.350

BioGRID (121): SCYL3 (Two-hybrid), SCYL3 (Two-hybrid), LHX8 (Two-hybrid), SCYL3 (Proximity Label-MS), SCYL3 (Proximity Label-MS), SCYL3 (Proximity Label-MS), SCYL3 (Affinity Capture-MS), SCYL3 (Proximity Label-MS), SCYL3 (Affinity Capture-MS), SCYL3 (Affinity Capture-MS), SCYL3 (Proximity Label-MS), SCYL3 (Proximity Label-MS), SCYL3 (Proximity Label-MS), SCYL3 (Two-hybrid), SCYL3 (Proximity Label-MS)

ESM2 similar proteins: A1L3L1, A2RT67, A3KPW7, A4IIA7, A8C750, A8C752, D2HNY3, E1BGQ2, E1C3P4, Q08CL8, Q08DZ8, Q0IHB3, Q149N8, Q1RMU2, Q1RMZ1, Q3MJ13, Q3T1H6, Q5F3F2, Q5RED8, Q5VVJ2, Q5ZJ87, Q66J91, Q69Z66, Q6AYF5, Q6DE97, Q6GR37, Q6P1E7, Q6PNC0, Q6YHU6, Q7TPQ3, Q8BKW4, Q8BXK4, Q8IWR0, Q8IYF3, Q8IZE3, Q8K2I9, Q8NA31, Q8NEN0, Q8NFZ0, Q96EW2

Diamond homologs: O13733, Q8IZE3, Q9DBQ7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 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	25.6×	2e-06
COPI-dependent Golgi-to-ER retrograde traffic	6	22.2×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
intra-Golgi vesicle-mediated transport	6	87.8×	2e-08
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	5	46.8×	7e-06
endoplasmic reticulum to Golgi vesicle-mediated transport	7	26.4×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4482 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:169864410:G:T	A305D	0.998
1:169876031:A:G	W138R	0.998
1:169876031:A:T	W138R	0.998
1:169859118:A:T	V412D	0.997
1:169878646:G:C	F113L	0.997
1:169878646:G:T	F113L	0.997
1:169878648:A:G	F113L	0.997
1:169878804:G:T	R61S	0.996
1:169859202:C:T	G384D	0.995
1:169859203:C:G	G384R	0.995
1:169862680:A:G	L358P	0.995
1:169878746:A:G	L80P	0.995
1:169862683:A:G	L357P	0.994
1:169862692:C:G	R354P	0.994
1:169866901:G:C	F270L	0.994
1:169866901:G:T	F270L	0.994
1:169866903:A:G	F270L	0.994
1:169866946:G:C	F255L	0.994
1:169866946:G:T	F255L	0.994
1:169866948:A:G	F255L	0.994
1:169878803:C:G	R61P	0.994
1:169859091:A:G	F421S	0.993
1:169859163:A:G	L397P	0.993
1:169859199:A:G	L385P	0.993
1:169859211:A:T	V381D	0.993
1:169864386:A:G	L313P	0.993
1:169870312:C:G	D190H	0.993
1:169878644:A:G	L114P	0.993
1:169859090:G:C	F421L	0.992
1:169859090:G:T	F421L	0.992

dbSNP variants (sampled 300 via entrez): RS1000003424 (1:169887288 G>C), RS1000035839 (1:169867959 T>C), RS1000054230 (1:169892581 G>A), RS1000062604 (1:169881596 C>G), RS1000214862 (1:169850981 T>C), RS1000225022 (1:169856679 T>A), RS1000258174 (1:169880884 C>A), RS1000284240 (1:169875191 A>G), RS1000383384 (1:169868260 C>T), RS1000414590 (1:169868579 A>C), RS1000522612 (1:169891968 A>C), RS1000624458 (1:169876258 G>A), RS1000628166 (1:169885422 G>A,T), RS1000667327 (1:169862235 T>C), RS1000758616 (1:169876597 T>C)

Disease associations

OMIM: gene MIM:608192 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010481_6	Acute anterior uveitis in ankylosing spondylitis	6.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, increases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
afimoxifene	decreases expression, decreases reaction	1
sodium arsenite	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression	1
Estrogens	decreases expression, decreases reaction	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TK22	HAP1 SCYL3 (-) 1	Cancer cell line	Male
CVCL_TK23	HAP1 SCYL3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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