STYXL2

Summary

STYXL2 (serine/threonine/tyrosine interacting like 2, HGNC:25034) is a protein-coding gene on chromosome 1q24.1, encoding Serine/threonine/tyrosine-interacting-like protein 2 (Q5VZP5). May be required for myofiber maturation.

Predicted to enable MAP kinase phosphatase activity and protein tyrosine/serine/threonine phosphatase activity. Predicted to be involved in negative regulation of MAPK cascade. Predicted to be located in sarcomere. Predicted to be active in cytoplasm.

Source: NCBI Gene 92235 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 268 total
• MANE Select transcript: NM_001080426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25034
Approved symbol	STYXL2
Name	serine/threonine/tyrosine interacting like 2
Location	1q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198842
Ensembl biotype	protein_coding
Entrez	92235

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000271385, ENST00000361200, ENST00000443333, ENST00000485151

RefSeq mRNA: 1 — MANE Select: NM_001080426 NM_001080426

CCDS: CCDS30932

Canonical transcript exons

ENST00000361200 — 6 exons

Exon	Start	End
ENSE00000958480	167119249	167119466
ENSE00001224282	167117328	167117559
ENSE00001445809	167113710	167113804
ENSE00001445810	167094834	167094959
ENSE00001445811	167094075	167094194
ENSE00001776510	167125787	167129165

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 99.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0838 / max 140.9263, expressed in 127 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6426	0.9866	114
6427	0.0973	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.45	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.06	gold quality
tibialis anterior	UBERON:0001385	98.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.43	gold quality
myocardium	UBERON:0002349	97.62	gold quality
deltoid	UBERON:0001476	97.56	gold quality
heart right ventricle	UBERON:0002080	97.37	gold quality
apex of heart	UBERON:0002098	97.37	gold quality
skeletal muscle tissue	UBERON:0001134	97.21	gold quality
quadriceps femoris	UBERON:0001377	97.02	gold quality
vastus lateralis	UBERON:0001379	96.71	gold quality
biceps brachii	UBERON:0001507	96.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.59	gold quality
gastrocnemius	UBERON:0001388	95.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.63	gold quality
cardiac ventricle	UBERON:0002082	94.74	gold quality
heart left ventricle	UBERON:0002084	94.68	gold quality
skeletal muscle organ	UBERON:0014892	94.54	gold quality
muscle of leg	UBERON:0001383	93.87	gold quality
body of tongue	UBERON:0011876	93.87	gold quality
muscle tissue	UBERON:0002385	92.65	gold quality
cardiac atrium	UBERON:0002081	92.07	gold quality
right atrium auricular region	UBERON:0006631	91.59	gold quality
heart	UBERON:0000948	90.25	gold quality
tongue	UBERON:0001723	84.60	gold quality
vena cava	UBERON:0004087	81.93	gold quality
descending thoracic aorta	UBERON:0002345	76.53	gold quality
thoracic aorta	UBERON:0001515	74.86	gold quality
ascending aorta	UBERON:0001496	74.66	gold quality
superior surface of tongue	UBERON:0007371	72.42	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting STYXL2, 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-4481	100.00	66.42	1669
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-6890-3P	97.50	65.71	997
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-301A-5P	96.88	68.07	931
HSA-MIR-301B-5P	96.88	67.75	946
HSA-MIR-1233-3P	96.81	65.44	573
HSA-MIR-597-3P	96.46	68.03	1035
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-6800-3P	96.15	65.16	461
HSA-MIR-1251-5P	95.78	64.10	374
HSA-MIR-4330	95.44	66.39	993

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000099889
mus_musculus	Styxl2	ENSMUSG00000026564
rattus_norvegicus	Styxl2	ENSRNOG00000003722

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), DUSP3 (ENSG00000108861), PTPMT1 (ENSG00000110536), DUSP16 (ENSG00000111266), EPM2A (ENSG00000112425), DUSP22 (ENSG00000112679), DUSP1 (ENSG00000120129), DUSP4 (ENSG00000120875), STYXL1 (ENSG00000127952), DUSP9 (ENSG00000130829), DUSP26 (ENSG00000133878), DUSP5 (ENSG00000138166), DUSP6 (ENSG00000139318), SSH2 (ENSG00000141298), DUSP10 (ENSG00000143507), DUSP15 (ENSG00000149599), DUSP2 (ENSG00000158050), KASH5 (ENSG00000161609), DUSP19 (ENSG00000162999), DUSP7 (ENSG00000164086), DUSP18 (ENSG00000167065), SSH3 (ENSG00000172830), DUSP8 (ENSG00000184545), DUSP28 (ENSG00000188542), DUSP29 (ENSG00000188716), DUSP21 (ENSG00000189037), STYX (ENSG00000198252), DUSP14 (ENSG00000276023), DUSP13A (ENSG00000293543)

Protein

Protein identifiers

Serine/threonine/tyrosine-interacting-like protein 2 — Q5VZP5 (reviewed: Q5VZP5)

Alternative names: Inactive dual specificity phosphatase 27

All UniProt accessions (1): Q5VZP5

UniProt curated annotations — full annotation on UniProt →

Function. May be required for myofiber maturation.

Subcellular location. Cytoplasm. Myofibril. Sarcomere.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.

RefSeq proteins (1): NP_001073895* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR020405	Atypical_DUSP_subfamA	Family
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily

Pfam: PF00782

UniProt features (37 total): compositionally biased region 15, region of interest 10, modified residue 5, sequence variant 5, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VZP5-F1	56.11	0.18

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 (5): 377, 433, 509, 985, 1036

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, MODULE_48, MODULE_95, DAIRKEE_CANCER_PRONE_RESPONSE_BPA_E2, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, GOMF_PROTEIN_TYROSINE_SERINE_THREONINE_PHOSPHATASE_ACTIVITY, GOMF_MAP_KINASE_PHOSPHATASE_ACTIVITY, MIKKELSEN_MCV6_LCP_WITH_H3K4ME3, MIKKELSEN_MEF_LCP_WITH_H3K4ME3, MIKKELSEN_IPS_LCP_WITH_H3K4ME3, MIKKELSEN_ES_LCP_WITH_H3K4ME3

GO Biological Process (3): negative regulation of MAPK cascade (GO:0043409), protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311)

GO Molecular Function (3): protein tyrosine/serine/threonine phosphatase activity (GO:0008138), MAP kinase phosphatase activity (GO:0033549), phosphatase activity (GO:0016791)

GO Cellular Component (2): cytoplasm (GO:0005737), sarcomere (GO:0030017)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	2
cellular anatomical structure	2
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
dephosphorylation	1
protein modification process	1
phosphate-containing compound metabolic process	1
phosphoric ester hydrolase activity	1
intracellular anatomical structure	1
myofibril	1

Protein interactions and networks

STRING

1180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STYXL2	KLHL38	Q2WGJ6	519
STYXL2	EFHB	Q8N7U6	516
STYXL2	YIF1B	Q5BJH7	454
STYXL2	DUSP11	O75319	412
STYXL2	LRFN4	Q6PJG9	405
STYXL2	SCLY	Q96I15	388
STYXL2	RAVER1	Q8IY67	380
STYXL2	IRAG1	Q9Y6F6	371
STYXL2	ESPNL	Q6ZVH7	363
STYXL2	BTBD17	A6NE02	359
STYXL2	FAT2	Q9NYQ8	348
STYXL2	MAOA	P21397	344
STYXL2	TTI2	Q6NXR4	340
STYXL2	GLRB	P48167	332
STYXL2	GUCY1A2	P33402	328

IntAct

3 interactions, top by confidence:

A	B	Type	Score
YPEL5	SYNCRIP	psi-mi:“MI:0914”(association)	0.510
STYXL2	YPEL5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): YPEL5 (Affinity Capture-MS), DUSP27 (Affinity Capture-MS), DUSP27 (Affinity Capture-MS), DUSP27 (Affinity Capture-MS), DUSP27 (Cross-Linking-MS (XL-MS)), TRDN (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1L8ER70, A1L253, A2AHC3, A5WUN7, B1AZP2, D4AEC2, O14490, P28290, P62024, P97836, P97839, Q148W8, Q14CH0, Q2KI52, Q2M3X8, Q3ZBW7, Q4KM62, Q4R2Y2, Q4R707, Q52KF3, Q5PQL8, Q5R3Z9, Q5RD34, Q5RJX2, Q5VUB5, Q5VZP5, Q5XII9, Q6GLU8, Q6NSV7, Q6P995, Q6PEI3, Q6RFY2, Q7T3E8, Q8BJ42, Q8BYK5, Q8C1B1, Q922B9, Q95X94, Q96BN6, Q96KR7

Diamond homologs: A4IHU7, F1QWM2, O09112, O13632, O55737, O95147, P0C591, P0C592, P0C593, P0C594, P0C595, P0C596, P0C597, P0C598, P0C599, P0C5A0, P0C5A1, P0C5A2, P28562, P28563, P51452, Q05922, Q13115, Q13202, Q148W8, Q16828, Q16829, Q17QJ3, Q17QM8, Q1LWL2, Q29RA3, Q2KJ36, Q39491, Q4KL92, Q4RQD3, Q4V7N3, Q54T76, Q54Y32, Q556Y8, Q55BI8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	234
Likely benign	16
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1065 predictions. Top by Δscore:

Variant	Effect	Δscore
1:167094956:GCCA:G	donor_gain	1.0000
1:167094960:G:GG	donor_gain	1.0000
1:167117322:CTCTA:C	acceptor_loss	1.0000
1:167117325:TAGA:T	acceptor_loss	1.0000
1:167117326:A:AG	acceptor_gain	1.0000
1:167117326:A:G	acceptor_loss	1.0000
1:167117327:G:GA	acceptor_gain	1.0000
1:167117327:GA:G	acceptor_gain	1.0000
1:167117555:GAGAA:G	donor_gain	1.0000
1:167117557:GAA:G	donor_gain	1.0000
1:167117560:G:GG	donor_gain	1.0000
1:167125780:A:AG	acceptor_gain	1.0000
1:167125783:TCAG:T	acceptor_loss	1.0000
1:167125784:CAGG:C	acceptor_loss	1.0000
1:167125785:A:AG	acceptor_gain	1.0000
1:167125785:AG:A	acceptor_gain	1.0000
1:167125785:AGG:A	acceptor_gain	1.0000
1:167125786:G:GC	acceptor_gain	1.0000
1:167125786:GG:G	acceptor_gain	1.0000
1:167125786:GGG:G	acceptor_gain	1.0000
1:167125786:GGGA:G	acceptor_gain	1.0000
1:167125786:GGGAA:G	acceptor_gain	1.0000
1:167094185:C:T	donor_gain	0.9900
1:167094191:AGAGG:A	donor_loss	0.9900
1:167094193:AG:A	donor_loss	0.9900
1:167094194:GGT:G	donor_loss	0.9900
1:167094195:GTGA:G	donor_loss	0.9900
1:167094196:T:A	donor_loss	0.9900
1:167094830:TCAGA:T	acceptor_gain	0.9900
1:167094831:CAG:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000070127 (1:167095668 T>C), RS1000173439 (1:167095570 A>T), RS1000268630 (1:167123924 T>C,G), RS1000335294 (1:167128983 A>G), RS1000336861 (1:167122900 C>G), RS1000385069 (1:167124194 G>A), RS1000604278 (1:167125659 T>C), RS1000809064 (1:167105679 C>A,T), RS1000885444 (1:167111861 C>T), RS1001121133 (1:167115162 C>G), RS1001223050 (1:167121129 C>T), RS1001300638 (1:167119733 G>A), RS1001465113 (1:167110100 G>T), RS1001524107 (1:167103996 T>C), RS1001531876 (1:167108840 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9TJ	Ubigene HEK293 STYXL2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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