DUSP13B

Summary

DUSP13B (dual specificity phosphatase 13B, HGNC:19681) is a protein-coding gene on chromosome 10q22.2, encoding Dual specificity protein phosphatase 13B (Q9UII6). Dual specificity phosphatase that dephosphorylates MAPK8/JNK and MAPK14/p38, but not MAPK1/ERK2, in vitro.

Members of the protein-tyrosine phosphatase superfamily cooperate with protein kinases to regulate cell proliferation and differentiation. This gene encodes a dual specificity phosphatase that acts on both phosphotyrosine and phosphoserine/threonine residues. The encoded protein is expressed in testis.

Source: NCBI Gene 51207 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_001363514

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19681
Approved symbol	DUSP13B
Name	dual specificity phosphatase 13B
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	TMDP, SKRP4
Ensembl gene	ENSG00000079393
Ensembl biotype	protein_coding
OMIM	613191
Entrez	51207

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000464872, ENST00000472493, ENST00000478873, ENST00000605915, ENST00000707120, ENST00000707121

RefSeq mRNA: 6 — MANE Select: NM_001363514 NM_001007273, NM_001320842, NM_001320843, NM_001363514, NM_001412227, NM_016364

CCDS: CCDS7346, CCDS86105

Canonical transcript exons

ENST00000478873 — 4 exons

Exon	Start	End
ENSE00001871026	75094436	75094878
ENSE00001903813	75099031	75099512
ENSE00003695869	75095575	75095795
ENSE00003701863	75097712	75097885

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 98.73.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2046 / max 99.1843, expressed in 275 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110137	0.5073	130
110135	0.2860	122
110136	0.2705	132
110134	0.0853	48
110132	0.0381	3
110133	0.0108	4
110131	0.0067	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	98.73	gold quality
gastrocnemius	UBERON:0001388	98.45	gold quality
triceps brachii	UBERON:0001509	97.71	gold quality
gluteal muscle	UBERON:0002000	97.35	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.18	gold quality
biceps brachii	UBERON:0001507	97.06	gold quality
vastus lateralis	UBERON:0001379	97.00	gold quality
skeletal muscle tissue	UBERON:0001134	96.94	gold quality
quadriceps femoris	UBERON:0001377	96.84	gold quality
muscle organ	UBERON:0001630	96.35	gold quality
muscle of leg	UBERON:0001383	96.12	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.10	gold quality
diaphragm	UBERON:0001103	95.45	gold quality
deltoid	UBERON:0001476	94.27	gold quality
body of tongue	UBERON:0011876	94.13	gold quality
tibialis anterior	UBERON:0001385	93.55	gold quality
apex of heart	UBERON:0002098	91.66	gold quality
left testis	UBERON:0004533	91.44	gold quality
right testis	UBERON:0004534	89.60	gold quality
muscle tissue	UBERON:0002385	88.46	gold quality
testis	UBERON:0000473	87.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.74	gold quality
heart left ventricle	UBERON:0002084	85.45	gold quality
cardiac ventricle	UBERON:0002082	85.08	gold quality
tongue	UBERON:0001723	85.04	gold quality
pancreatic ductal cell	CL:0002079	82.76	silver quality
heart right ventricle	UBERON:0002080	81.50	gold quality
right atrium auricular region	UBERON:0006631	80.75	gold quality
cardiac atrium	UBERON:0002081	78.50	gold quality
heart	UBERON:0000948	77.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.27
E-CURD-11	no	29.15

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• identified a gene on chromosome 10q22.2 using alternative ORFs to encode two distinct DSPs: the testis and skeletal muscle-specific TMDP and a novel muscle-restricted DSP(MDSP) (PMID:15252030)
• Here, we report the crystal structure of human TMDP at a resolution of 2.4 A. In spite of high sequence similarity with other DSPs, the crystal structure of TMDP shows distinct structural motifs and surface propertie (PMID:17044055)
• data suggest an important role for DUSP13B in protection from external stress during spermatogenesis (PMID:21360282)
• Overexpression of dual-specificity phosphatases 4 and 13 attenuates transforming growth factor beta1-induced migration and drug resistance in A549 cells in vitro. (PMID:35338857)
• Systemic analysis identifying PVT1/DUSP13 axis for microvascular invasion in hepatocellular carcinoma. (PMID:36524545)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dusp13a	ENSDARG00000061498
danio_rerio	si:dkey-24f15.2	ENSDARG00000094665
danio_rerio		ENSDARG00000111496
		ENSDARG00000112352
mus_musculus	Dusp13b	ENSMUSG00000021768
rattus_norvegicus	Dusp13b	ENSRNOG00000060401

Paralogs (31): 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), STYXL2 (ENSG00000198842), DUSP14 (ENSG00000276023), DUSP13A (ENSG00000293543)

Protein

Protein identifiers

Dual specificity protein phosphatase 13B — Q9UII6 (reviewed: Q9UII6)

Alternative names: Dual specificity phosphatase SKRP4, Testis- and skeletal-muscle-specific DSP

All UniProt accessions (4): Q9UII6, A0A9L9PXN7, E9PSD4, U3KQA1

UniProt curated annotations — full annotation on UniProt →

Function. Dual specificity phosphatase that dephosphorylates MAPK8/JNK and MAPK14/p38, but not MAPK1/ERK2, in vitro. Exhibits intrinsic phosphatase activity towards both phospho-seryl/threonyl and -tyrosyl residues, with similar specific activities in vitro.

Tissue specificity. Highly expressed in the testis (at protein level). Also found in the skeletal muscle.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UII6-1	1, TMDP	yes
Q9UII6-4	4, TMDP-L2
Q9UII6-5	5

RefSeq proteins (6): NP_001007274, NP_001307771, NP_001307772, NP_001350443, NP_001399156, NP_057448 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR020405	Atypical_DUSP_subfamA	Family
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily

Pfam: PF00782

Catalyzed reactions (Rhea), 3 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (27 total): helix 9, strand 7, sequence variant 3, turn 2, splice variant 2, chain 1, domain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2PQ5	X-RAY DIFFRACTION	2.3
2GWO	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UII6-F1	90.56	0.78

Functional residue map

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

Catalytic / active sites (1): 138 (phosphocysteine intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, AP1_01, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, CCATCCA_MIR432, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, YGACNNYACAR_UNKNOWN, TGANTCA_AP1_C, NRF2_Q4, GOBP_DEPHOSPHORYLATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_PROTEIN_DEPHOSPHORYLATION, CCAGGTT_MIR490, NFE2_01, AP1FJ_Q2

GO Biological Process (5): protein dephosphorylation (GO:0006470), spermatogenesis (GO:0007283), dephosphorylation (GO:0016311), negative regulation of MAPK cascade (GO:0043409), meiotic cell cycle (GO:0051321)

GO Molecular Function (8): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), phosphatase activity (GO:0016791), MAP kinase phosphatase activity (GO:0033549), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	4
dephosphorylation	1
protein modification process	1
developmental process involved in reproduction	1
male gamete generation	1
phosphate-containing compound metabolic process	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
phosphoric ester hydrolase activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP13B	AP3M1	Q9Y2T2	475
DUSP13B	SAMD8	Q96LT4	451
DUSP13B	KAT6B	Q8WYB5	447
DUSP13B	LYZL4	Q96KX0	405
DUSP13B	DUSP11	O75319	403
DUSP13B	TMEM244	Q5VVB8	395
DUSP13B	TPPP	O94811	389
DUSP13B	PTP4A2	Q12974	378
DUSP13B	DUSP1	P28562	369
DUSP13B	C19orf18	Q8NEA5	367
DUSP13B	KRT36	O76013	359
DUSP13B	AP3M2	P53677	358
DUSP13B	C1orf115	Q9H7X2	357
DUSP13B	BNIP1	Q12981	353
DUSP13B	RASGEF1C	Q8N431	353

IntAct

47 interactions, top by confidence:

A	B	Type	Score
DUSP13B	LMNA	psi-mi:“MI:0915”(physical association)	0.780
LMNA	DUSP13B	psi-mi:“MI:0915”(physical association)	0.780
CALCOCO1	DUSP13B	psi-mi:“MI:0915”(physical association)	0.720
DUSP13B	CALCOCO1	psi-mi:“MI:0915”(physical association)	0.720
HOOK2	DUSP13B	psi-mi:“MI:0915”(physical association)	0.560
CARD9	DUSP13B	psi-mi:“MI:0915”(physical association)	0.560
DUSP13B	CARD9	psi-mi:“MI:0915”(physical association)	0.560
SH2B2	DUSP13B	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG4	DUSP13B	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	DUSP13B	psi-mi:“MI:0915”(physical association)	0.560
ZRANB1	DUSP13B	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	DUSP13B	psi-mi:“MI:0915”(physical association)	0.560
INCA1	DUSP13B	psi-mi:“MI:0915”(physical association)	0.560
CCDC85B	DUSP13B	psi-mi:“MI:0915”(physical association)	0.370
DUSP13B	SH2B2	psi-mi:“MI:0915”(physical association)	0.000
DUSP13B	PLEKHG4	psi-mi:“MI:0915”(physical association)	0.000
DUSP13B	CARD9	psi-mi:“MI:0915”(physical association)	0.000
DUSP13B	CALCOCO1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (114): DUSP13 (Two-hybrid), DUSP13 (Two-hybrid), CALCOCO1 (Two-hybrid), CARD9 (Two-hybrid), DUSP13 (Two-hybrid), NAGLU (Affinity Capture-MS), NUP98 (Proximity Label-MS), NUP107 (Proximity Label-MS), RPGRIP1L (Proximity Label-MS), DUSP13 (Affinity Capture-MS), DUSP13 (Affinity Capture-MS), DCTPP1 (Affinity Capture-MS), HLA-DRB5 (Affinity Capture-MS), KCTD6 (Affinity Capture-MS), ISCA2 (Affinity Capture-MS)

ESM2 similar proteins: A2AA28, A4FV42, A4FV98, A6NDG6, D3YWP0, D3ZVU9, O15315, O35719, O70277, O75382, O94759, P21964, P57775, P81799, Q2TBS1, Q3UGX3, Q4R3I0, Q5E9V4, Q5H879, Q5RJL2, Q5SUV1, Q6DC64, Q7Z624, Q86WI3, Q86XA0, Q8BNV1, Q8C436, Q8CIW5, Q8IZ69, Q8N8L6, Q8N9F0, Q8VCX6, Q8WXB1, Q96AZ1, Q96FB5, Q96RR1, Q9BQD7, Q9BRQ3, Q9BUU2, Q9CQL0

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	2
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

484 predictions. Top by Δscore:

Variant	Effect	Δscore
10:75095569:GTGCA:G	donor_loss	1.0000
10:75095570:TGCAC:T	donor_loss	1.0000
10:75095572:CA:C	donor_loss	1.0000
10:75095573:ACCT:A	donor_loss	1.0000
10:75095574:C:A	donor_loss	1.0000
10:75095791:CGTAC:C	acceptor_gain	1.0000
10:75095792:GTAC:G	acceptor_gain	1.0000
10:75095793:TAC:T	acceptor_gain	1.0000
10:75095794:AC:A	acceptor_gain	1.0000
10:75095795:CC:C	acceptor_gain	1.0000
10:75095796:C:CC	acceptor_gain	1.0000
10:75097706:A:AC	donor_gain	1.0000
10:75097707:C:CC	donor_gain	1.0000
10:75097707:CT:C	donor_gain	1.0000
10:75097707:CTCA:C	donor_gain	1.0000
10:75097710:A:AC	donor_gain	1.0000
10:75097711:C:CA	donor_gain	1.0000
10:75097711:CG:C	donor_gain	1.0000
10:75097711:CGCAT:C	donor_gain	1.0000
10:75094875:CGGC:C	acceptor_gain	0.9900
10:75094876:GGCCT:G	acceptor_loss	0.9900
10:75094878:CCTG:C	acceptor_loss	0.9900
10:75094879:C:CC	acceptor_gain	0.9900
10:75094879:CTGTA:C	acceptor_loss	0.9900
10:75094880:T:G	acceptor_loss	0.9900
10:75095575:C:G	donor_loss	0.9900
10:75095630:A:AC	donor_gain	0.9900
10:75095631:C:CC	donor_gain	0.9900
10:75095796:C:T	acceptor_gain	0.9900
10:75097704:TTAC:T	donor_loss	0.9900

AlphaMissense

2161 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:75094733:G:C	F180L	0.996
10:75094733:G:T	F180L	0.996
10:75094735:A:G	F180L	0.996
10:75094783:C:G	A164P	0.994
10:75095652:T:A	D106V	0.993
10:75094844:G:C	S143R	0.992
10:75094844:G:T	S143R	0.992
10:75094846:T:G	S143R	0.992
10:75094852:C:A	G141W	0.992
10:75094759:G:T	R172S	0.991
10:75094845:C:A	S143I	0.991
10:75095652:T:G	D106A	0.991
10:75095651:G:C	D106E	0.990
10:75095651:G:T	D106E	0.990
10:75094817:G:C	F152L	0.989
10:75094817:G:T	F152L	0.989
10:75094819:A:G	F152L	0.989
10:75095653:C:G	D106H	0.989
10:75094734:A:G	F180S	0.988
10:75095738:A:C	N77K	0.988
10:75095738:A:T	N77K	0.988
10:75094839:G:A	S145F	0.987
10:75095745:A:T	V75D	0.986
10:75094843:G:T	R144S	0.985
10:75094852:C:G	G141R	0.985
10:75094852:C:T	G141R	0.985
10:75095652:T:C	D106G	0.985
10:75094859:A:C	C138W	0.984
10:75094851:C:T	G141E	0.982
10:75094722:A:T	L184H	0.981

dbSNP variants (sampled 300 via entrez): RS1000064627 (10:75097578 C>T), RS1000095697 (10:75102933 C>T), RS1000275529 (10:75104568 G>A,T), RS1000283755 (10:75104872 C>A), RS1000665172 (10:75107180 C>A,G), RS1000827471 (10:75100286 C>G,T), RS1000915079 (10:75094502 T>C), RS1001074494 (10:75096163 G>A), RS1001116263 (10:75100627 C>A), RS1001168816 (10:75096654 T>G), RS1001259827 (10:75100522 G>A,C), RS1001442136 (10:75110677 A>G), RS1001497796 (10:75105332 G>T), RS1001697805 (10:75099521 C>T), RS1001747613 (10:75110463 C>T)

Disease associations

OMIM: gene MIM:613191 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006585_1584	Blood protein levels	2.000000e-72
GCST008129_50	Body mass index	5.000000e-08
GCST008839_73	Height	1.000000e-10
GCST010242_206	HDL cholesterol levels	6.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	4
Cyclosporine	decreases methylation, increases expression	2
Aflatoxin B1	increases expression	2
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects expression	1
Dimethylnitrosamine	increases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, affects response to substance	1
Methapyrilene	increases expression	1
Methyl Methanesulfonate	increases expression	1
Silicon Dioxide	decreases expression	1
Tetradecanoylphorbol Acetate	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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