DUSP16

Summary

DUSP16 (dual specificity phosphatase 16, HGNC:17909) is a protein-coding gene on chromosome 12p13.2, encoding Dual specificity protein phosphatase 16 (Q9BY84). Dual specificity protein phosphatase involved in the inactivation of MAP kinases.

This gene encodes a mitogen-activated protein kinase phosphatase that is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. The encoded protein specifically regulates the c-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways.

Source: NCBI Gene 80824 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 88 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_030640

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17909
Approved symbol	DUSP16
Name	dual specificity phosphatase 16
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MKP-7, KIAA1700, MKP7
Ensembl gene	ENSG00000111266
Ensembl biotype	protein_coding
OMIM	607175
Entrez	80824

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000228862, ENST00000298573, ENST00000536236, ENST00000539940, ENST00000541207, ENST00000545864, ENST00000877434, ENST00000877435, ENST00000877436, ENST00000877437, ENST00000877438, ENST00000877439, ENST00000877440, ENST00000877441, ENST00000924713

RefSeq mRNA: 1 — MANE Select: NM_030640 NM_030640

CCDS: CCDS8650

Canonical transcript exons

ENST00000298573 — 7 exons

Exon	Start	End
ENSE00000721801	12519862	12520000
ENSE00001370962	12520871	12521463
ENSE00002206195	12473282	12478015
ENSE00003553653	12487028	12487187
ENSE00003665317	12480223	12480346
ENSE00003691068	12500519	12500682
ENSE00003894196	12562117	12562863

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 98.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0982 / max 271.3708, expressed in 1718 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129751	7.4700	1456
129748	2.0723	1022
129750	1.3724	626
129744	0.9374	268
129745	0.6925	367
129749	0.5089	297
129752	0.3351	159
129738	0.2944	88
129753	0.2826	124
129746	0.1841	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	98.46	gold quality
corpus callosum	UBERON:0002336	93.32	gold quality
adrenal gland	UBERON:0002369	92.56	gold quality
ventricular zone	UBERON:0003053	92.43	gold quality
tonsil	UBERON:0002372	92.26	gold quality
right adrenal gland cortex	UBERON:0035827	92.18	gold quality
left adrenal gland	UBERON:0001234	92.09	gold quality
right adrenal gland	UBERON:0001233	91.92	gold quality
left adrenal gland cortex	UBERON:0035825	91.66	gold quality
liver	UBERON:0002107	91.28	gold quality
islet of Langerhans	UBERON:0000006	91.25	gold quality
duodenum	UBERON:0002114	90.20	gold quality
colonic epithelium	UBERON:0000397	90.09	gold quality
rectum	UBERON:0001052	89.51	gold quality
ganglionic eminence	UBERON:0004023	89.51	gold quality
embryo	UBERON:0000922	89.50	gold quality
calcaneal tendon	UBERON:0003701	88.74	gold quality
pancreas	UBERON:0001264	87.77	gold quality
right lobe of liver	UBERON:0001114	86.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.48	gold quality
skeletal muscle tissue	UBERON:0001134	86.41	gold quality
gall bladder	UBERON:0002110	86.38	gold quality
prostate gland	UBERON:0002367	85.65	gold quality
vermiform appendix	UBERON:0001154	85.58	gold quality
body of pancreas	UBERON:0001150	85.51	gold quality
lower esophagus mucosa	UBERON:0035834	85.51	gold quality
urinary bladder	UBERON:0001255	85.45	gold quality
vagina	UBERON:0000996	84.45	gold quality
bone marrow cell	CL:0002092	84.36	gold quality
muscle tissue	UBERON:0002385	84.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, GATA6, HAND1, HAND2, NFAT5, PRDM1, TBX21

miRNA regulators (miRDB)

168 targeting DUSP16, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3143	99.93	71.96	3104

Literature-anchored findings (GeneRIF, showing 19)

• context-dependent role for DUSP16 on cell transformation and apoptosis. (PMID:14586399)
• activation of the ERK pathway strongly blocks JNK activation through stabilization of MKP-7 mediated by phosphorylation (PMID:15689616)
• MKP7 binds beta-arrestin 2 via amino acids 394-443 of MKP7, the same region that interacts with JIP-1 (PMID:15888437)
• identification of an intricate SDF-1alpha-induced signaling cascade that involves eNOS, JNK3, and MKP7and enhances endothelial migration (PMID:19307591)
• MKP-7 down-regulates ERK-dependent gene expression by blocking nuclear accumulation of phospho-ERK. (PMID:20122898)
• DUSP16 is a new epigenetically regulated determinant of JNK activation in BL. (PMID:20551953)
• MKP-7, a negative regulator of JNK, regulates VCAM-1 expression in activated endothelial cells through IRF-1 but not GATA6. (PMID:22182512)
• DUSPs 10 and 16 are positive regulators of activation, apparently acting by modulating cross-talk between the p38 and ERK pathways. (PMID:22245064)
• Data indicate that LRP6, BCL2L14, DUSP16, CREBL2, and CDKN1B were involed in centromeric (12p11.21-12p13.2) deletion in ETV6-RUNX1 B-cell precursor acute lymphoblastic leukemia (BCP-ALL). (PMID:23077088)
• Data indicate that the activities of phosphoprotein phosphatases MKP5 and MKP7 were determined in the system. (PMID:23233447)
• PPARdelta-mediated messenger RNA stabilization of mitogen-activated protein kinase phosphatase (MKP)-7 was responsible for the GW501516-mediated inhibition of JNK signaling. (PMID:23639976)
• analysis of the interaction of the MAPK binding domain of DUSP16 with p38alpha (PMID:23926106)
• The DUSP16 ablation leads to a G1/S transition arrest, reduced incorporation of 5-bromodeoxyuridine, enhanced senescence-associated beta-galactosidase activity, and formation of senescence-associated heterochromatic foci. (PMID:26381291)
• The crystal structure of JNK1 bound to the catalytic domain of MKP7 at 2.4-A resolution, providing high-resolution structural insight into the FXF-docking interaction, is reported. (PMID:26988444)
• Chemotherapy increased DUSP9 expression and decreased DUSP16 expression in a HIF1-dependent manner. (PMID:29880481)
• DUSP16 is a regulator of human hematopoietic stem and progenitor cells and promotes their expansion ex vivo. (PMID:33077868)
• CircDUSP16 Contributes to Cell Development in Esophageal Squamous Cell Carcinoma by Regulating miR-497-5p/TKTL1 Axis. (PMID:33326930)
• DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death. (PMID:33863904)
• A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK binding. (PMID:36272649)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dusp16	ENSDARG00000102474
mus_musculus	Dusp16	ENSMUSG00000030203
rattus_norvegicus	Dusp16	ENSRNOG00000006628

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), DUSP3 (ENSG00000108861), PTPMT1 (ENSG00000110536), 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 16 — Q9BY84 (reviewed: Q9BY84)

Alternative names: Mitogen-activated protein kinase phosphatase 7

All UniProt accessions (2): Q9BY84, F5H5X4

UniProt curated annotations — full annotation on UniProt →

Function. Dual specificity protein phosphatase involved in the inactivation of MAP kinases. Dephosphorylates MAPK10 bound to ARRB2.

Subunit / interactions. Interacts with ARRB2.

Subcellular location. Cytoplasm. Nucleus. Cytoplasmic vesicle.

Post-translational modifications. Phosphorylated at Ser-446 by MAPK1/ERK2, which prevents its degradation, and thereby stabilizes it and blocks JNK MAPK activity. (Microbial infection) Acetylated at Lys-55 by the M.tuberculosis Eis protein; this leads to the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS (reactive oxygen species) generation for enhanced intracellular survival of M.tuberculosis.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BY84-1	1	yes
Q9BY84-2	2

RefSeq proteins (1): NP_085143* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR001763	Rhodanese-like_dom	Domain
IPR008343	MKP	Family
IPR016130	Tyr_Pase_AS	Active_site
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily

Pfam: PF00581, 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 (44 total): helix 15, strand 11, compositionally biased region 4, modified residue 3, region of interest 3, domain 2, splice variant 2, sequence variant 2, chain 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2VSW	X-RAY DIFFRACTION	2.2
4YR8	X-RAY DIFFRACTION	2.4
3TG3	X-RAY DIFFRACTION	2.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY84-F1	60.81	0.32

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): 244 (phosphocysteine intermediate)

Post-translational modifications (3): 55, 446, 501

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-112409	RAF-independent MAPK1/3 activation
R-HSA-5675221	Negative regulation of MAPK pathway
R-HSA-9636569	Suppression of autophagy
R-HSA-9652817	Signaling by MAPK mutants

MSigDB gene sets: 300 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, KEGG_MAPK_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, RASHI_NFKB1_TARGETS, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, WANG_LMO4_TARGETS_DN, FOSTER_TOLERANT_MACROPHAGE_UP, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_UP, GOBP_DEPHOSPHORYLATION, OUYANG_PROSTATE_CANCER_PROGRESSION_UP, HAN_JNK_SINGALING_UP, ATGTACA_MIR493

GO Biological Process (4): signal transduction (GO:0007165), dephosphorylation (GO:0016311), negative regulation of MAPK cascade (GO:0043409), protein dephosphorylation (GO:0006470)

GO Molecular Function (13): phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine/threonine phosphatase activity (GO:0008330), JUN kinase binding (GO:0008432), phosphatase activity (GO:0016791), MAP kinase tyrosine/serine/threonine phosphatase activity (GO:0017017), MAP kinase tyrosine phosphatase activity (GO:0033550), mitogen-activated protein kinase p38 binding (GO:0048273), mitogen-activated protein kinase binding (GO:0051019), protein carrier activity (GO:0140597), protein tyrosine phosphatase activity (GO:0004725), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
MAPK1/MAPK3 signaling	1
RAF/MAP kinase cascade	1
Response of Mtb to phagocytosis	1
Oncogenic MAPK signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	3
cellular anatomical structure	3
protein kinase binding	2
MAP kinase phosphatase activity	2
cytoplasm	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phosphate-containing compound metabolic process	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
dephosphorylation	1
protein modification process	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoric ester hydrolase activity	1
protein tyrosine/serine/threonine phosphatase activity	1
protein tyrosine phosphatase activity	1
mitogen-activated protein kinase binding	1
molecular carrier activity	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

1442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP16	POLR1F	Q3B726	793
DUSP16	IP6K2	Q9UHH9	701
DUSP16	EXT2	Q93063	677
DUSP16	MAPK8	P45983	638
DUSP16	MAPK8IP1	Q9UQF2	631
DUSP16	MAPK12	P53778	569
DUSP16	MAPK13	O15264	567
DUSP16	MAPK9	P45984	552
DUSP16	MAPK11	Q15759	548
DUSP16	DUSP7	Q16829	526
DUSP16	NKX2-1	P43699	511
DUSP16	ARRB2	P32121	507
DUSP16	DUSP9	Q99956	505
DUSP16	BORCS5	Q969J3	479
DUSP16	JUN	P05412	478

IntAct

25 interactions, top by confidence:

A	B	Type	Score
MAPK9	DUSP16	psi-mi:“MI:0915”(physical association)	0.800
DUSP16	MAPK9	psi-mi:“MI:0914”(association)	0.800
MAPK9	WDR62	psi-mi:“MI:0914”(association)	0.800
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
MAPK8	DUSP16	psi-mi:“MI:0915”(physical association)	0.560
DUSP16	WFS1	psi-mi:“MI:0915”(physical association)	0.560
GABARAP	DUSP16	psi-mi:“MI:0915”(physical association)	0.400
DUSP16	ERBB4	psi-mi:“MI:0915”(physical association)	0.370
DUSP16	TUBAL3	psi-mi:“MI:0914”(association)	0.350
MAPK14	PRKY	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
DUSP16	MEIOC	psi-mi:“MI:0914”(association)	0.350
ROCK2	POLR1C	psi-mi:“MI:0914”(association)	0.350
SLC7A9	CDC7	psi-mi:“MI:0914”(association)	0.350
TRIM54	DUSP16	psi-mi:“MI:0915”(physical association)	0.000
DUSP16	MAPK9	psi-mi:“MI:0915”(physical association)	0.000
DUSP16	MAPK8	psi-mi:“MI:0915”(physical association)	0.000
MAPK14	DUSP16	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (268): DUSP16 (Affinity Capture-MS), DUSP16 (Synthetic Lethality), MAPK14 (Affinity Capture-MS), MAPK9 (Affinity Capture-MS), DUSP16 (Affinity Capture-MS), MLF1 (Affinity Capture-MS), PTGES3 (Affinity Capture-MS), MAPK9 (Affinity Capture-MS), NXF2 (Affinity Capture-MS), MAPK8 (Affinity Capture-MS), AIP (Affinity Capture-MS), KCTD20 (Affinity Capture-MS), YWHAB (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), HIGD1A (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTY4, A2VD01, A5PMU4, A8E4V2, D2HNW6, E1BEQ5, O54972, O95644, P16236, P59281, P70365, P97305, Q12968, Q13191, Q13469, Q13905, Q15788, Q1LY51, Q2VPU4, Q3LRZ1, Q3TTA7, Q3U182, Q4PJW2, Q4VCS5, Q60591, Q61122, Q66IV1, Q68FF7, Q6DFR2, Q6GQL0, Q6NYU6, Q6ZNC4, Q80TM6, Q80VG1, Q8HWS3, Q8IXK0, Q8IY63, Q8K4S7, Q8N228, Q8VHG2

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

4 interactions.

A	Effect	B	Mechanism
DUSP16	down-regulates	MAPK14	dephosphorylation
DUSP16	“down-regulates activity”	MTOR	dephosphorylation
DUSP16	up-regulates	MAPK8IP1	binding
MAPK1	“up-regulates quantity by stabilization”	DUSP16	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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
Cellular responses to stress	5	13.2×	9e-04
Cellular responses to stimuli	5	11.2×	9e-04
Infectious disease	5	8.9×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — COADREAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1596 predictions. Top by Δscore:

Variant	Effect	Δscore
12:12480345:CT:C	acceptor_gain	1.0000
12:12480347:C:CC	acceptor_gain	1.0000
12:12487023:CTTA:C	donor_loss	1.0000
12:12487024:TTAC:T	donor_loss	1.0000
12:12487025:TAC:T	donor_loss	1.0000
12:12487026:A:AC	donor_gain	1.0000
12:12487027:C:CC	donor_gain	1.0000
12:12487027:CCA:C	donor_gain	1.0000
12:12487185:CTC:C	acceptor_gain	1.0000
12:12487186:TC:T	acceptor_gain	1.0000
12:12487186:TCC:T	acceptor_loss	1.0000
12:12487187:CCTA:C	acceptor_gain	1.0000
12:12487188:C:CC	acceptor_gain	1.0000
12:12506879:T:TA	donor_gain	1.0000
12:12519856:CCTTA:C	donor_loss	1.0000
12:12519858:TTACC:T	donor_loss	1.0000
12:12519860:A:AT	donor_loss	1.0000
12:12519861:CC:C	donor_loss	1.0000
12:12519996:TCAAC:T	acceptor_gain	1.0000
12:12519997:CAAC:C	acceptor_gain	1.0000
12:12519997:CAACC:C	acceptor_gain	1.0000
12:12520000:CCTG:C	acceptor_loss	1.0000
12:12520001:C:CC	acceptor_gain	1.0000
12:12520001:CTGA:C	acceptor_loss	1.0000
12:12520002:T:G	acceptor_loss	1.0000
12:12562115:A:AC	donor_gain	1.0000
12:12562116:C:CC	donor_gain	1.0000
12:12478011:CAAAT:C	acceptor_gain	0.9900
12:12478013:AAT:A	acceptor_gain	0.9900
12:12478014:AT:A	acceptor_gain	0.9900

AlphaMissense

4354 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:12477959:A:G	L291P	1.000
12:12477959:A:T	L291H	1.000
12:12477965:C:T	G289D	1.000
12:12477966:C:G	G289R	1.000
12:12477968:A:G	L288P	1.000
12:12477970:A:C	F287L	1.000
12:12477970:A:T	F287L	1.000
12:12477971:A:C	F287C	1.000
12:12477971:A:G	F287S	1.000
12:12477972:A:C	F287V	1.000
12:12477972:A:G	F287L	1.000
12:12477972:A:T	F287I	1.000
12:12477973:A:C	N286K	1.000
12:12477973:A:T	N286K	1.000
12:12477977:A:G	F285S	1.000
12:12477979:G:C	N284K	1.000
12:12477979:G:T	N284K	1.000
12:12477981:T:C	N284D	1.000
12:12477983:G:A	P283L	1.000
12:12477983:G:C	P283R	1.000
12:12477983:G:T	P283Q	1.000
12:12477984:G:A	P283S	1.000
12:12477984:G:C	P283A	1.000
12:12477984:G:T	P283T	1.000
12:12477989:A:C	I281R	1.000
12:12477989:A:T	I281K	1.000
12:12477997:T:A	R278S	1.000
12:12477997:T:G	R278S	1.000
12:12477998:C:G	R278T	1.000
12:12477999:T:C	R278G	1.000

dbSNP variants (sampled 300 via entrez): RS1000000850 (12:12556661 C>A,T), RS1000002329 (12:12539854 C>A), RS1000020873 (12:12558941 C>A,T), RS1000070796 (12:12489428 T>C), RS1000095362 (12:12556565 A>AC), RS1000135766 (12:12562343 G>C), RS1000148635 (12:12473204 T>G), RS1000156448 (12:12533513 G>A), RS1000162918 (12:12561947 A>C,G), RS1000187101 (12:12514990 T>C), RS1000194519 (12:12524844 T>C), RS1000207717 (12:12513905 C>T), RS1000248401 (12:12550898 A>G), RS1000296227 (12:12561713 A>T), RS1000328159 (12:12483564 G>A)

Disease associations

OMIM: gene MIM:607175 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003485_3	Response to fenofibrate (HDL cholesterol levels)	9.000000e-06
GCST007267_100	Systolic blood pressure	1.000000e-09
GCST008839_219	Height	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007805	HDL cholesterol change measurement
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	3
bisphenol A	increases methylation, decreases expression, increases expression	2
sulforaphane	decreases expression, increases expression	2
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
Arsenic	increases methylation, affects cotreatment, decreases expression, increases abundance	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
methylmercuric chloride	increases expression	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	decreases expression	1
clothianidin	decreases expression	1
torcetrapib	increases expression	1
asparanin A	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Troglitazone	increases expression	1
Vorinostat	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7P1	Ubigene A-549 DUSP16 KO	Cancer cell line	Male
CVCL_D8KF	Ubigene HCT 116 DUSP16 KO	Cancer cell line	Male
CVCL_D9DS	Ubigene HEK293 DUSP16 KO	Transformed cell line	Female
CVCL_E0C2	Ubigene HeLa DUSP16 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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