DUSP21

Summary

DUSP21 (dual specificity phosphatase 21, HGNC:20476) is a protein-coding gene on chromosome Xp11.3, encoding Dual specificity protein phosphatase 21 (Q9H596). Protein phosphatase component of the sperm flagellar doublet microtubules.

This gene encodes a member of the dual specificity phosphatase family, specifically the low molecular weight dual specificity phosphatase family. The encoded protein localizes to both the cytoplasm and the nucleus and functions to remove phosphate groups from phosphotyrosine and phosphothreonine residues.

Source: NCBI Gene 63904 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total — 1 pathogenic
• MANE Select transcript: NM_022076

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20476
Approved symbol	DUSP21
Name	dual specificity phosphatase 21
Location	Xp11.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000189037
Ensembl biotype	protein_coding
OMIM	300678
Entrez	63904

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000339042

RefSeq mRNA: 1 — MANE Select: NM_022076 NM_022076

CCDS: CCDS14264

Canonical transcript exons

ENST00000339042 — 1 exons

Exon	Start	End
ENSE00001366587	44844021	44844888

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 92.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0645 / max 14.6347, expressed in 29 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196072	0.0645	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.59	gold quality
sperm	CL:0000019	85.56	gold quality
male germ cell	CL:0000015	82.55	gold quality
left testis	UBERON:0004533	75.59	gold quality
right testis	UBERON:0004534	74.01	gold quality
testis	UBERON:0000473	72.94	gold quality
adult organism	UBERON:0007023	51.89	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
epithelial cell of pancreas	CL:0000083	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
pancreatic ductal cell	CL:0002079	48.96	silver quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
quadriceps femoris	UBERON:0001377	48.70	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.44	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.45	gold quality
thymus	UBERON:0002370	47.42	gold quality
kidney epithelium	UBERON:0004819	47.39	gold quality
nephron tubule	UBERON:0001231	47.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting DUSP21, 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-4482-3P	99.98	72.50	3147
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-513B-3P	98.76	68.12	1577

Literature-anchored findings (GeneRIF, showing 1)

• DUSP21 plays an important role in sustaining hepatocellular carcinoma (HCC) cell proliferation and may thus act as a potential therapeutic target in HCC treatment. (PMID:23929653)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dusp21	ENSMUSG00000025043
rattus_norvegicus	Dusp21	ENSRNOG00000024138

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

Protein

Protein identifiers

Dual specificity protein phosphatase 21 — Q9H596 (reviewed: Q9H596)

Alternative names: Low molecular weight dual specificity phosphatase 21

All UniProt accessions (1): Q9H596

UniProt curated annotations — full annotation on UniProt →

Function. Protein phosphatase component of the sperm flagellar doublet microtubules. May act as a regulator of sperm motility by mediating dephosphorylation of sperm doublet microtubule proteins. Can dephosphorylate single and diphosphorylated synthetic MAPK peptides, with preference for the phosphotyrosine and diphosphorylated forms over phosphothreonine.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules.

Subcellular location. Cytoplasm. Nucleus. Mitochondrion inner membrane. Cytoskeleton. Flagellum axoneme.

Tissue specificity. Expressed in testis.

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

RefSeq proteins (1): NP_071359* (*=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
IPR020420	Atypical_DUSP_subfamB	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 (7 total): sequence variant 2, chain 1, domain 1, region of interest 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H596-F1	92.15	0.85

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): 106 (phosphocysteine intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, HFH3_01, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_DEPHOSPHORYLATION, GOBP_PROTEIN_DEPHOSPHORYLATION, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_INNER_MEMBRANE, GOCC_NUCLEOLUS, GOCC_CYTOPLASMIC_MICROTUBULE, GOCC_CILIUM, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PROTEIN_SERINE_THREONINE_PHOSPHATASE_ACTIVITY

GO Biological Process (4): flagellated sperm motility (GO:0030317), peptidyl-tyrosine dephosphorylation (GO:0035335), protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311)

GO Molecular Function (6): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), MAP kinase tyrosine/serine/threonine phosphatase activity (GO:0017017), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), sperm flagellum (GO:0036126), axonemal A tubule inner sheath (GO:0160111), mitochondrion (GO:0005739), cytoskeleton (GO:0005856), cilium (GO:0005929), membrane (GO:0016020), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
phosphoprotein phosphatase activity	2
intracellular membrane-bounded organelle	2
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
protein dephosphorylation	1
dephosphorylation	1
protein modification process	1
phosphate-containing compound metabolic process	1
protein tyrosine/serine/threonine phosphatase activity	1
MAP kinase phosphatase activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
intracellular organelle lumen	1
9+2 motile cilium	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	1
cytoplasm	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP21	DUSP11	O75319	487
DUSP21	OR10H5	Q8NGA6	480
DUSP21	DIPK2B	Q9H7Y0	480
DUSP21	KCNE5	Q9UJ90	458
DUSP21	MAPK8	P45983	448
DUSP21	VWA5B1	Q5TIE3	433
DUSP21	CPXCR1	Q8N123	432
DUSP21	S100G	P29377	421
DUSP21	HDHD5	Q9BXW7	418
DUSP21	XKR5	Q6UX68	411
DUSP21	MAPK14	Q16539	409
DUSP21	PPP1R2C	O14990	406
DUSP21	KRABD4	Q5JUW0	405
DUSP21	XAGE5	Q8WWM1	395
DUSP21	PAGE4	O60829	389

IntAct

92 interactions, top by confidence:

A	B	Type	Score
GORASP2	DUSP21	psi-mi:“MI:0915”(physical association)	0.780
DUSP21	GORASP2	psi-mi:“MI:0915”(physical association)	0.780
DUSP21	TEX11	psi-mi:“MI:0915”(physical association)	0.560
TEX11	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
MAP2K5	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
GET4	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
RFX6	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
DUSP21	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
DUSP21	ATP23	psi-mi:“MI:0915”(physical association)	0.560
KRT33B	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
EYA2	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
KLHL20	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
CTBP2	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
KRTAP11-1	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
DUSP21	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
OIP5	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
MYO15B	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
SUOX	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
FAAP20	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
USP2	DUSP21	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (91): DUSP21 (Two-hybrid), DUSP21 (Two-hybrid), DUSP21 (Affinity Capture-MS), GANAB (Affinity Capture-MS), TIMMDC1 (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), DUSP28 (Affinity Capture-MS), ARF5 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), PDCD6 (Affinity Capture-MS), RCN1 (Affinity Capture-MS), COX4I1 (Affinity Capture-MS), DUSP23 (Affinity Capture-MS), TMEM70 (Affinity Capture-MS), NDUFA11 (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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	18
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2426670	NC_000023.10:g.(?43515590)(44970656_?)del	Pathogenic

SpliceAI

166 predictions. Top by Δscore:

Variant	Effect	Δscore
X:44844229:AAT:A	acceptor_gain	0.8400
X:44844231:T:TA	acceptor_gain	0.7000
X:44844168:GGGT:G	acceptor_gain	0.6600
X:44844229:A:AG	acceptor_gain	0.6100
X:44844167:AG:A	acceptor_gain	0.6000
X:44844168:GG:G	acceptor_gain	0.6000
X:44844227:GCAAT:G	acceptor_gain	0.5900
X:44844226:A:AG	acceptor_gain	0.5500
X:44844227:G:GG	acceptor_gain	0.5500
X:44844299:TGG:T	donor_gain	0.5100
X:44844223:C:T	acceptor_gain	0.5000
X:44844268:A:AG	acceptor_gain	0.5000
X:44844163:TCTCA:T	acceptor_loss	0.4700
X:44844164:CTCA:C	acceptor_loss	0.4700
X:44844165:TCAGG:T	acceptor_loss	0.4700
X:44844167:A:AG	acceptor_gain	0.4700
X:44844167:A:T	acceptor_loss	0.4700
X:44844168:G:GA	acceptor_loss	0.4700
X:44844168:G:GG	acceptor_gain	0.4700
X:44844159:A:AG	acceptor_gain	0.4500
X:44844160:T:G	acceptor_gain	0.4400
X:44844849:G:GG	donor_gain	0.4400
X:44844325:GGCAT:G	donor_gain	0.4300
X:44844848:A:AG	donor_gain	0.4300
X:44844399:T:A	acceptor_gain	0.4200
X:44844646:CCG:C	donor_loss	0.4200
X:44844648:GG:G	donor_loss	0.4200
X:44844650:T:A	donor_loss	0.4200
X:44844160:TCA:T	acceptor_gain	0.4100
X:44844227:GCA:G	acceptor_gain	0.4100

AlphaMissense

1258 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:44844526:G:C	A132P	0.996
X:44844577:T:C	F149L	0.996
X:44844579:T:A	F149L	0.996
X:44844579:T:G	F149L	0.996
X:44844463:A:C	S111R	0.994
X:44844464:G:T	S111I	0.994
X:44844465:C:A	S111R	0.994
X:44844465:C:G	S111R	0.994
X:44844470:C:T	S113F	0.991
X:44844550:C:A	R140S	0.991
X:44844565:C:T	P145S	0.991
X:44844287:T:A	V52D	0.990
X:44844590:T:C	L153P	0.990
X:44844527:C:A	A132D	0.989
X:44844566:C:A	P145H	0.989
X:44844226:A:C	S32R	0.988
X:44844228:C:A	S32R	0.988
X:44844228:C:G	S32R	0.988
X:44844481:T:C	C117R	0.988
X:44844483:C:G	C117W	0.988
X:44844590:T:A	L153H	0.988
X:44844450:C:G	C106W	0.987
X:44844578:T:C	F149S	0.987
X:44844440:T:C	L103P	0.986
X:44844458:G:A	G109E	0.986
X:44844466:C:A	R112S	0.985
X:44844488:C:A	A119E	0.985
X:44844494:T:C	L121P	0.985
X:44844602:A:T	E157V	0.985
X:44844280:G:C	A50P	0.984

dbSNP variants (sampled 300 via entrez): RS1000001311 (X:44843082 G>A), RS1002040084 (X:44843184 C>T), RS1003595529 (X:44845376 CTT>C), RS1007060580 (X:44842583 A>G), RS1007077154 (X:44842292 G>A), RS1009549529 (X:44843635 G>A), RS1010013795 (X:44844846 G>A), RS1010598211 (X:44842730 T>C), RS1010987189 (X:44843099 G>C), RS1011991935 (X:44844485 T>G), RS1013126866 (X:44845290 T>C), RS1013876482 (X:44842661 A>C,T), RS1018056207 (X:44842031 A>C), RS1021997289 (X:44843107 G>C), RS1023420565 (X:44844514 T>C)

Disease associations

OMIM: gene MIM:300678 | disease phenotypes: MIM:300867

GenCC curated gene-disease

Mondo (1): Kabuki syndrome 2 (MONDO:0010465)

Orphanet (1): Kabuki syndrome (Orphanet:2322)

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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
vanadyl sulfate	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	decreases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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