DUSP29

Summary

DUSP29 (dual specificity phosphatase 29, HGNC:23481) is a protein-coding gene on chromosome 10q22.2, encoding Dual specificity phosphatase 29 (Q68J44). Dual specificity phosphatase able to dephosphorylate phosphotyrosine, phosphoserine and phosphothreonine residues within the same substrate, with a preference for phosphotyrosine as a substrate.

Enables protein homodimerization activity and protein tyrosine/serine/threonine phosphatase activity. Involved in protein dephosphorylation. Part of protein-containing complex.

Source: NCBI Gene 338599 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_001003892

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23481
Approved symbol	DUSP29
Name	dual specificity phosphatase 29
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	DUSP27
Ensembl gene	ENSG00000188716
Ensembl biotype	protein_coding
OMIM	618574
Entrez	338599

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000338487, ENST00000944289

RefSeq mRNA: 2 — MANE Select: NM_001003892 NM_001003892, NM_001384909

CCDS: CCDS31223

Canonical transcript exons

ENST00000338487 — 4 exons

Exon	Start	End
ENSE00001378512	75043797	75044017
ENSE00001391268	75037472	75038077
ENSE00001414754	75058315	75058548
ENSE00003920390	75073569	75073642

Expression profiles

Bgee: expression breadth broad, 55 present calls, max score 94.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1538 / max 43.4780, expressed in 28 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110129	0.0781	19
110130	0.0758	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	94.52	gold quality
gastrocnemius	UBERON:0001388	94.24	gold quality
muscle of leg	UBERON:0001383	92.75	gold quality
skeletal muscle tissue	UBERON:0001134	90.52	gold quality
muscle tissue	UBERON:0002385	76.37	gold quality
apex of heart	UBERON:0002098	65.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	54.15	gold quality
heart left ventricle	UBERON:0002084	53.29	gold quality
colonic epithelium	UBERON:0000397	42.50	gold quality
bone marrow cell	CL:0002092	42.20	gold quality
heart	UBERON:0000948	40.87	gold quality
placenta	UBERON:0001987	40.07	gold quality
pituitary gland	UBERON:0000007	40.00	gold quality
adenohypophysis	UBERON:0002196	39.07	gold quality
lymph node	UBERON:0000029	38.48	gold quality
smooth muscle tissue	UBERON:0001135	37.87	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
bone marrow	UBERON:0002371	34.83	gold quality
vermiform appendix	UBERON:0001154	34.10	silver quality
urinary bladder	UBERON:0001255	33.02	gold quality
prefrontal cortex	UBERON:0000451	32.02	silver quality
blood	UBERON:0000178	31.57	gold quality
minor salivary gland	UBERON:0001830	31.13	gold quality
saliva-secreting gland	UBERON:0001044	30.96	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
lower esophagus muscularis layer	UBERON:0035833	30.68	gold quality
multicellular organism	UBERON:0000468	30.67	gold quality
lower esophagus	UBERON:0013473	30.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.20

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• a cytosolic enzyme, expressed in skeletal muscle, liver and adipose tissue, suggesting its possible role in energy metabolism (PMID:17498703)
• Here, the overexpression, purification and structure determination of DUPD1 (also known as DUSP27) at 2.38 A resolution are presented. (PMID:21543850)
• Dual-specificity phosphatase 29 is induced during neurogenic skeletal muscle atrophy and attenuates glucocorticoid receptor activity in muscle cell culture. (PMID:32639872)
• Dual-specificity phosphatases 13 and 27 as key switches in muscle stem cell transition from proliferation to differentiation. (PMID:38975693)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-121a2.2	ENSDARG00000039682
danio_rerio	si:dkeyp-27c8.1	ENSDARG00000067808
danio_rerio	si:dkeyp-27c8.1	ENSDARG00000092956
danio_rerio	si:dkey-194e6.2	ENSDARG00000095001
danio_rerio		ENSDARG00000112213
mus_musculus	Dusp29	ENSMUSG00000063821
rattus_norvegicus	Dusp29	ENSRNOG00000013034

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), DUSP21 (ENSG00000189037), STYX (ENSG00000198252), STYXL2 (ENSG00000198842), DUSP14 (ENSG00000276023), DUSP13A (ENSG00000293543)

Protein

Protein identifiers

Dual specificity phosphatase 29 — Q68J44 (reviewed: Q68J44)

Alternative names: Dual specificity phosphatase 27, Dual specificity phosphatase DUPD1

All UniProt accessions (1): Q68J44

UniProt curated annotations — full annotation on UniProt →

Function. Dual specificity phosphatase able to dephosphorylate phosphotyrosine, phosphoserine and phosphothreonine residues within the same substrate, with a preference for phosphotyrosine as a substrate. Involved in the modulation of intracellular signaling cascades. In skeletal muscle regulates systemic glucose homeostasis by activating, AMPK, an energy sensor protein kinase. Affects MAP kinase signaling though modulation of the MAPK1/2 cascade in skeletal muscle promoting muscle cell differentiation, development and atrophy.

Subunit / interactions. Homodimer. Interacts with PRKAA2.

Subcellular location. Cytoplasm. Nucleus.

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

RefSeq proteins (2): NP_001003892, NP_001371838 (=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 (24 total): helix 9, strand 6, sequence variant 2, chain 1, domain 1, turn 1, region of interest 1, compositionally biased region 1, active site 1, binding site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2Y96	X-RAY DIFFRACTION	2.38

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68J44-F1	87.10	0.72

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): 147 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (1): 146–153

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_CARBOHYDRATE_HOMEOSTASIS, GOBP_DEPHOSPHORYLATION, GOBP_PROTEIN_DEPHOSPHORYLATION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_ERK1_AND_ERK2_CASCADE, GOBP_MUSCLE_CELL_DIFFERENTIATION, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_PROTEIN_HOMODIMERIZATION_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS

GO Biological Process (6): protein dephosphorylation (GO:0006470), glucose homeostasis (GO:0042593), muscle cell differentiation (GO:0042692), negative regulation of MAPK cascade (GO:0043409), negative regulation of ERK1 and ERK2 cascade (GO:0070373), dephosphorylation (GO:0016311)

GO Molecular Function (9): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), MAP kinase phosphatase activity (GO:0033549), protein homodimerization activity (GO:0042803), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	4
dephosphorylation	1
protein modification process	1
carbohydrate homeostasis	1
cell differentiation	1
muscle structure development	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
phosphate-containing compound metabolic process	1
identical protein binding	1
protein dimerization activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

1242 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP29	DUSP23	Q9BVJ7	451
DUSP29	MS4A8	Q9BY19	440
DUSP29	EPM2A	O95278	407
DUSP29	DYSF	O75923	378
DUSP29	RPL5	P46777	371
DUSP29	FKBP1A	P20071	366
DUSP29	DUSP11	O75319	357
DUSP29	SAMD8	Q96LT4	357
DUSP29	FKBP1C	Q5VVH2	353
DUSP29	SLC6A19	Q695T7	352
DUSP29	AMPD1	P23109	350
DUSP29	SERPINA10	Q9UK55	341
DUSP29	PPP1R7	Q15435	337
DUSP29	PGP	A6NDG6	335
DUSP29	REXO2	Q9Y3B8	334

IntAct

73 interactions, top by confidence:

A	B	Type	Score
DUSP29	TEPSIN	psi-mi:“MI:0915”(physical association)	0.560
DUSP29	NIF3L1	psi-mi:“MI:0915”(physical association)	0.560
DUSP29	PICK1	psi-mi:“MI:0915”(physical association)	0.560
STX11	DUSP29	psi-mi:“MI:0915”(physical association)	0.560
DUSP29	LNX1	psi-mi:“MI:0915”(physical association)	0.560
RNF40	DUSP29	psi-mi:“MI:0915”(physical association)	0.560
DUSP29	GOLGA6A	psi-mi:“MI:0915”(physical association)	0.560
TCF4	DUSP29	psi-mi:“MI:0915”(physical association)	0.560
DUSP29	CNTROB	psi-mi:“MI:0915”(physical association)	0.560
ASPA	DUSP29	psi-mi:“MI:0915”(physical association)	0.560
DUSP29	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
DUSP29	C17orf75	psi-mi:“MI:0915”(physical association)	0.560
PSMB5	DUSP29	psi-mi:“MI:0915”(physical association)	0.560
SRSF11	DUSP29	psi-mi:“MI:0915”(physical association)	0.560
ARPC3	DUSP29	psi-mi:“MI:0915”(physical association)	0.560
DUSP29	NOC4L	psi-mi:“MI:0915”(physical association)	0.560
POLR2G	DUSP29	psi-mi:“MI:0915”(physical association)	0.560
DUSP29	PDHB	psi-mi:“MI:0914”(association)	0.420
DUSP29	PDHB	psi-mi:“MI:2364”(proximity)	0.420
OR51B5	DUSP29	psi-mi:“MI:0915”(physical association)	0.400
RXRB	DUSP29	psi-mi:“MI:0915”(physical association)	0.400
DUSP29	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
DUSP29	AATK	psi-mi:“MI:0915”(physical association)	0.370
DUSP29	ERBB3	psi-mi:“MI:0915”(physical association)	0.370
DUSP29	ROR1	psi-mi:“MI:0915”(physical association)	0.370
DUSP29	ROR2	psi-mi:“MI:0915”(physical association)	0.370
DUSP29	IGF1R	psi-mi:“MI:0915”(physical association)	0.370
DUSP29	PTK7	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (41): DUPD1 (Two-hybrid), GPD2 (Affinity Capture-MS), PDHB (Affinity Capture-MS), RB1CC1 (Proximity Label-MS), PDHB (Proximity Label-MS), DUPD1 (Two-hybrid), DUPD1 (Two-hybrid), DUPD1 (Two-hybrid), DUPD1 (Two-hybrid), DUPD1 (Two-hybrid), DUPD1 (Two-hybrid), DUPD1 (Two-hybrid), FASN (Affinity Capture-MS), GSR (Affinity Capture-MS), PDHB (Affinity Capture-MS)

ESM2 similar proteins: A4D256, A4IHU7, O14830, O35239, O35385, O95147, P0C591, P0C592, P0C593, P0C594, P0C595, P0C596, P0C597, P0C598, P0C599, P0C5A0, P0C5A1, P0C5A2, P43378, P51452, Q16828, Q17QM8, Q29RA3, Q2KJ36, Q4KL92, Q4RQD3, Q566R7, Q5RD73, Q5XHB2, Q641Z2, Q64346, Q68J44, Q6AXW7, Q6GQJ8, Q86BN8, Q8BK84, Q8K4T5, Q8WTR2, Q8WUK0, Q90W58

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

355 predictions. Top by Δscore:

Variant	Effect	Δscore
10:75043795:A:AC	donor_gain	1.0000
10:75043796:C:CT	donor_gain	1.0000
10:75043796:CT:C	donor_gain	1.0000
10:75058311:TTA:T	donor_loss	1.0000
10:75058312:TA:T	donor_loss	1.0000
10:75058313:A:AC	donor_gain	1.0000
10:75058313:ACT:A	donor_gain	1.0000
10:75058314:C:CT	donor_gain	1.0000
10:75058314:CT:C	donor_gain	1.0000
10:75058314:CTC:C	donor_gain	1.0000
10:75058314:CTCA:C	donor_gain	1.0000
10:75058314:CTCAT:C	donor_gain	1.0000
10:75058317:ATCG:A	donor_gain	1.0000
10:75058318:T:C	donor_gain	1.0000
10:75038078:CTGC:C	acceptor_loss	0.9900
10:75043790:CTCTT:C	donor_loss	0.9900
10:75043791:TCTTA:T	donor_loss	0.9900
10:75043792:CTTA:C	donor_loss	0.9900
10:75043793:TTA:T	donor_loss	0.9900
10:75043794:TACT:T	donor_loss	0.9900
10:75043795:ACTGT:A	donor_loss	0.9900
10:75043796:CTGT:C	donor_gain	0.9900
10:75043796:CTGTG:C	donor_gain	0.9900
10:75058317:A:AC	donor_gain	0.9900
10:75058376:T:TA	donor_gain	0.9900
10:75038073:CTTAC:C	acceptor_gain	0.9800
10:75038074:TTAC:T	acceptor_gain	0.9800
10:75038079:T:C	acceptor_loss	0.9800
10:75043796:CTG:C	donor_gain	0.9800
10:75043812:G:C	donor_gain	0.9800

AlphaMissense

1446 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:75037932:A:C	F189L	0.999
10:75037932:A:T	F189L	0.999
10:75037934:A:G	F189L	0.999
10:75043874:T:A	D115V	0.997
10:75043874:T:C	D115G	0.997
10:75037933:A:G	F189S	0.996
10:75037958:G:T	R181S	0.996
10:75037982:C:G	A173P	0.996
10:75038043:G:C	S152R	0.996
10:75038043:G:T	S152R	0.996
10:75038045:T:G	S152R	0.996
10:75038058:G:C	C147W	0.996
10:75038060:A:G	C147R	0.996
10:75043873:G:C	D115E	0.996
10:75043873:G:T	D115E	0.996
10:75043874:T:G	D115A	0.996
10:75038051:C:A	G150C	0.995
10:75038065:A:T	V145D	0.995
10:75043960:G:C	N86K	0.995
10:75043960:G:T	N86K	0.995
10:75037945:G:T	P185Q	0.994
10:75038051:C:G	G150R	0.994
10:75043964:A:G	L85P	0.994
10:75037934:A:C	F189V	0.993
10:75037946:G:A	P185S	0.993
10:75037951:A:T	V183D	0.993
10:75038044:C:A	S152I	0.993
10:75038050:C:A	G150V	0.993
10:75038050:C:T	G150D	0.993
10:75038059:C:T	C147Y	0.993

dbSNP variants (sampled 300 via entrez): RS1000083110 (10:75068892 A>G), RS1000235775 (10:75051830 G>A), RS1000319233 (10:75039580 G>A), RS1000349506 (10:75063520 T>C), RS1000397318 (10:75075314 T>A), RS1000649532 (10:75064616 C>T), RS1000720749 (10:75063151 T>A), RS1000787849 (10:75062076 G>C), RS1000802321 (10:75046105 C>A), RS1000824950 (10:75073306 C>T), RS1001006106 (10:75045842 G>T), RS1001083286 (10:75064769 C>G,T), RS1001090129 (10:75062271 A>C), RS1001110117 (10:75056412 T>C), RS1001139999 (10:75046118 AAAAAG>A)

Disease associations

OMIM: gene MIM:618574 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002696_5	Anxiety disorder	6.000000e-06
GCST008839_73	Height	1.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
Fulvestrant	affects cotreatment, decreases methylation	1
Ethanol	increases expression	1
Benzo(a)pyrene	affects methylation	1
Lipopolysaccharides	increases expression, affects response to substance	1
Testosterone	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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