DUSP9

Summary

DUSP9 (dual specificity phosphatase 9, HGNC:3076) is a protein-coding gene on chromosome Xq28, encoding Dual specificity protein phosphatase 9 (Q99956). Inactivates MAP kinases.

The protein encoded by this gene 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. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which is associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product shows selectivity for members of the ERK family of MAP kinases and is localized to the cytoplasm and nucleus. Aberrant expression of this gene is associated with type 2 diabetes and cancer progression in several cell types. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 1852 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_001318503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3076
Approved symbol	DUSP9
Name	dual specificity phosphatase 9
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	MKP-4, MKP4
Ensembl gene	ENSG00000130829
Ensembl biotype	protein_coding
OMIM	300134
Entrez	1852

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000342782, ENST00000370167, ENST00000477033, ENST00000879027, ENST00000879028, ENST00000879029, ENST00000879030, ENST00000879031, ENST00000879032, ENST00000879033, ENST00000938706

RefSeq mRNA: 2 — MANE Select: NM_001318503 NM_001318503, NM_001395

CCDS: CCDS14724

Canonical transcript exons

ENST00000342782 — 4 exons

Exon	Start	End
ENSE00000897466	153649232	153649687
ENSE00001418629	153647203	153647425
ENSE00001451988	153647919	153648326
ENSE00001889058	153649980	153651326

Expression profiles

Bgee: expression breadth ubiquitous, 107 present calls, max score 92.10.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3567 / max 282.6802, expressed in 500 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198088	1.7069	400
198085	0.4447	177
198086	0.0790	31
198084	0.0560	22
198089	0.0488	20
198083	0.0213	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	92.10	gold quality
renal medulla	UBERON:0000362	91.18	gold quality
adult mammalian kidney	UBERON:0000082	88.44	gold quality
frontal pole	UBERON:0002795	87.95	gold quality
paraflocculus	UBERON:0005351	86.64	gold quality
middle frontal gyrus	UBERON:0002702	85.75	gold quality
metanephros cortex	UBERON:0010533	84.42	gold quality
kidney	UBERON:0002113	83.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.56	gold quality
endometrium epithelium	UBERON:0004811	82.37	gold quality
metanephros	UBERON:0000081	78.43	gold quality
nephron tubule	UBERON:0001231	78.42	silver quality
kidney epithelium	UBERON:0004819	77.42	silver quality
cortex of kidney	UBERON:0001225	77.04	gold quality
pancreatic ductal cell	CL:0002079	75.45	silver quality
adrenal tissue	UBERON:0018303	74.55	gold quality
Brodmann (1909) area 10	UBERON:0013541	74.01	gold quality
renal glomerulus	UBERON:0000074	73.19	silver quality
metanephric glomerulus	UBERON:0004736	73.07	silver quality
nucleus accumbens	UBERON:0001882	72.40	gold quality
buccal mucosa cell	CL:0002336	71.91	gold quality
triceps brachii	UBERON:0001509	70.18	gold quality
gluteal muscle	UBERON:0002000	70.04	gold quality
amygdala	UBERON:0001876	69.90	gold quality
caudate nucleus	UBERON:0001873	69.17	gold quality
cortical plate	UBERON:0005343	68.79	gold quality
cingulate cortex	UBERON:0003027	68.67	gold quality
anterior cingulate cortex	UBERON:0009835	68.59	gold quality
putamen	UBERON:0001874	68.56	gold quality
right frontal lobe	UBERON:0002810	65.08	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	1241.72
E-HCAD-24	yes	1029.06
E-HCAD-10	yes	13.12
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting DUSP9, 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-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-3125	99.14	68.49	2269

Literature-anchored findings (GeneRIF, showing 13)

• microtubule disruption by MKP4 provides a novel mechanism for tumor suppression by a cytosolic MKP (PMID:18006813)
• 2.7 A resolution crystal structure of the catalytic domain of MKP-4 (MKP-4C) is presented (PMID:21206059)
• DUSP9/MKP-4 is a bona fide target of PKA signaling and attenuation of DUSP9/MKP-4 function can mediate cross-talk between the PKA pathway and MAPK signaling through both ERK1/2 and p38alpha in vivo (PMID:21908610)
• decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. (PMID:21943117)
• The DUSP9 locus is a common susceptibility locus for type 2 diabetes across different ethnicities, and 6 loci identified in South Asian genome-wide association studies also have significant effect on susceptibility to Japanese type 2 diabetes. (PMID:23029454)
• DUSP9 protein levels were markedly suppressed in severe pre-eclampsia, but not in severe IUGR. This suppression might be attributable to the prolonged hypoxic conditions found in pre-eclampsia. (PMID:23276385)
• A possible use for DUSP9 as CIMP marker. (PMID:24838152)
• The results of this study, combined with previous studies, suggested that therapeutic intervention to increase the expression or activity of DUSP9 may enable the activation of anti-proliferation signals in malignant cells. (PMID:25998184)
• Chemotherapy increased DUSP9 expression and decreased DUSP16 expression in a HIF1-dependent manner. (PMID:29880481)
• SNP rs5945326 in DUSP9 gene may be not associated with the risk of gestational diabetes mellitus (PMID:30835362)
• DUSP9 upregulation in the placenta of gestational diabetes mellitus pregnant women may promote insulin resistance, which may correlate with the occurrence of gestational diabetes. (PMID:31772940)
• DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases. (PMID:34768967)
• Genetic Variants of HNF4A, WFS1, DUSP9, FTO, and ZFAND6 Genes Are Associated with Prediabetes Susceptibility and Inflammatory Markers in the Saudi Arabian Population. (PMID:36980809)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dusp9	ENSMUSG00000031383
rattus_norvegicus	Dusp9	ENSRNOG00000055185

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), DUSP3 (ENSG00000108861), PTPMT1 (ENSG00000110536), DUSP16 (ENSG00000111266), EPM2A (ENSG00000112425), DUSP22 (ENSG00000112679), DUSP1 (ENSG00000120129), DUSP4 (ENSG00000120875), STYXL1 (ENSG00000127952), 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 9 — Q99956 (reviewed: Q99956)

Alternative names: Mitogen-activated protein kinase phosphatase 4

All UniProt accessions (1): Q99956

UniProt curated annotations — full annotation on UniProt →

Function. Inactivates MAP kinases. Has a specificity for the ERK family.

Subcellular location. Cytoplasm.

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

RefSeq proteins (2): NP_001305432, NP_001386 (=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
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily

Pfam: PF00581, PF00782

Enzyme classification (BRENDA):

• EC 3.1.3.48 — protein-tyrosine-phosphatase (BRENDA: 59 organisms, 501 substrates, 1326 inhibitors, 270 Km, 165 kcat entries)

Substrate kinetics (BRENDA)

70 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYL PHOSPHATE	0.0008–148	84
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.0039–0.862	27
P-NITROPHENYL PHOSPHATE	0.0024–10	20
DADEPYLIPQQG	0.0003–0.1	12
PHOSPHOTYROSINE	0.012–30	11
LYSOZYME	0.0003–0.012	5
MYELIN BASIC PROTEIN	0.0001–0.022	5
ACETYL-DADEPY-NH2	0.0228–0.219	4
ACETYL-DADEPYL-NH2	1.1–97.5	4
4,6,8-TRIMETHYL-2-OXO-2H-CHROMEN-7-YL DIHYDROGEN	0.02–0.156	3
SASASPYSASA	0.53–2.3	3
1-NAPHTHYL PHOSPHATE	1.19–1.88	2
3,6-FLUORESCEIN DIPHOSPHATE	15–19	2
4-METHYLUMBELLIFERYL PHOSPHATE	0.953–2.41	2
BOVINE SERUM ALBUMIN	0.0001–0.0003	2

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): strand 7, helix 7, modified residue 3, domain 2, chain 1, turn 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2HXP	X-RAY DIFFRACTION	1.83
3LJ8	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99956-F1	77.23	0.43

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): 290 (phosphocysteine intermediate)

Post-translational modifications (3): 16, 262, 351

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 132 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, KEGG_MAPK_SIGNALING_PATHWAY, ATACCTC_MIR202, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, BROWNE_HCMV_INFECTION_48HR_DN, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_JNK_CASCADE, HEN1_01, LIAO_METASTASIS

GO Biological Process (8): MAPK cascade (GO:0000165), protein dephosphorylation (GO:0006470), signal transduction (GO:0007165), JNK cascade (GO:0007254), ERK1 and ERK2 cascade (GO:0070371), negative regulation of ERK1 and ERK2 cascade (GO:0070373), dephosphorylation (GO:0016311), negative regulation of MAPK cascade (GO:0043409)

GO Molecular Function (9): phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), protein tyrosine/threonine phosphatase activity (GO:0008330), MAP kinase tyrosine/serine/threonine phosphatase activity (GO:0017017), MAP kinase tyrosine phosphatase activity (GO:0033550), protein tyrosine phosphatase activity (GO:0004725), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
MAPK1/MAPK3 signaling	1
RAF/MAP kinase cascade	1
Oncogenic MAPK signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	4
MAPK cascade	3
MAP kinase phosphatase activity	2
cellular anatomical structure	2
intracellular signaling cassette	1
dephosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	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
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
phosphatase activity	1
catalytic activity, acting on a protein	1
protein tyrosine/serine/threonine phosphatase activity	1
protein tyrosine phosphatase activity	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1330 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP9	IRS1	P35568	580
DUSP9	MAPK1	P28482	568
DUSP9	MAPK3	P27361	539
DUSP9	DUSP8	Q13202	522
DUSP9	CDKAL1	Q5VV42	518
DUSP9	DUSP10	Q9Y6W6	513
DUSP9	ZBED3	Q96IU2	507
DUSP9	DUSP16	Q9BY84	505
DUSP9	KLF14	Q8TD94	484
DUSP9	PPEF1	O14829	482
DUSP9	CDC123	O75794	477
DUSP9	ARAP1	Q96P48	474
DUSP9	MAPK14	Q16539	467
DUSP9	MAPK7	Q13164	467
DUSP9	ZFAND6	Q6FIF0	452

IntAct

33 interactions, top by confidence:

A	B	Type	Score
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
DUSP9	MAPK14	psi-mi:“MI:0915”(physical association)	0.780
MAPK14	DUSP9	psi-mi:“MI:0915”(physical association)	0.780
DUSP9	MAPK1	psi-mi:“MI:0915”(physical association)	0.740
MAPK14	RPS6KA5	psi-mi:“MI:0914”(association)	0.660
DUSP9	MAPK3	psi-mi:“MI:2364”(proximity)	0.610
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
DUSP9	Mapk14	psi-mi:“MI:0915”(physical association)	0.530
Mapk14	DUSP9	psi-mi:“MI:0203”(dephosphorylation reaction)	0.530
DUSP9	AATK	psi-mi:“MI:0915”(physical association)	0.370
CDK4	DUSP9	psi-mi:“MI:0915”(physical association)	0.370
DUSP9	GSK3B	psi-mi:“MI:0915”(physical association)	0.370
Mapk3	DUSP9	psi-mi:“MI:0915”(physical association)	0.370
DUSP9	Mapk1	psi-mi:“MI:0915”(physical association)	0.370
STK4	EIF3CL	psi-mi:“MI:0914”(association)	0.350
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
M	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
M2	ESYT2	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
DUSP7	DUSP9	psi-mi:“MI:0914”(association)	0.350
MAPK14	PRKY	psi-mi:“MI:0914”(association)	0.350
MAPK1	SEC16A	psi-mi:“MI:0914”(association)	0.350
DUSP9	LTN1	psi-mi:“MI:0914”(association)	0.350
MAPK3	HMMR	psi-mi:“MI:0914”(association)	0.350
PRKY	METTL15	psi-mi:“MI:0914”(association)	0.350
HNRNPCL2	SMCHD1	psi-mi:“MI:0914”(association)	0.350
MAPK1	SPAG9	psi-mi:“MI:0914”(association)	0.350

BioGRID (137): DUSP9 (Affinity Capture-MS), DUSP9 (Affinity Capture-MS), DUSP9 (Co-localization), DUSP9 (Affinity Capture-MS), ELP2 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), IKBKAP (Affinity Capture-MS), LTN1 (Affinity Capture-MS), MAPK1 (Affinity Capture-MS), MAPK11 (Affinity Capture-MS), MAPK14 (Affinity Capture-MS), MAPK3 (Affinity Capture-MS), PRIM1 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS), DUSP6 (Affinity Capture-MS)

ESM2 similar proteins: O43304, O54838, O75038, O95382, P0C591, P0C592, P0C594, P0C595, P0C596, P28562, P28563, Q05922, Q05923, Q13115, Q14451, Q16690, Q16828, Q16829, Q17QJ3, Q2KJ36, Q4RQD3, Q561R2, Q5FVI9, Q5R6H6, Q60806, Q61152, Q62767, Q63340, Q64346, Q64623, Q68J44, Q6B8I0, Q6PAT0, Q8BFV3, Q8BK84, Q90W58, Q91790, Q91Z46, Q99952, Q99956

Diamond homologs: A0A7H0DN78, P07239, P0C597, P0C598, P0C5A0, P0C5A1, P0DOQ5, P0DOQ6, P20495, P28191, P28562, P28563, P29074, P51452, P80994, Q05923, Q13115, Q16690, Q16828, Q2KJ36, Q4RQD3, Q54R42, Q54T76, Q5RD73, Q62767, Q64346, Q64623, Q6B8I0, Q6B8I1, Q84JU4, Q85297, Q8BFV3, Q90W58, Q91790, Q99956, Q9D0T2, Q9DBB1, Q9J592, Q9M8K7, Q9PW71

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
DUSP9	down-regulates	MAPK1	binding
DUSP9	down-regulates	MAPK1	dephosphorylation
DUSP9	down-regulates	MAPK3	binding
DUSP9	down-regulates	Gbeta	binding
DUSP9	down-regulates	ERK1/2	binding
DUSP9	down-regulates	MAPK14	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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
ERK/MAPK targets	5	176.8×	1e-08
MAPK targets/ Nuclear events mediated by MAP kinases	5	143.1×	2e-08
Nuclear Events (kinase and transcription factor activation)	5	91.1×	1e-07
MAP kinase activation	5	81.2×	2e-07
Interleukin-17 signaling	5	66.8×	4e-07
Toll Like Receptor 10 (TLR10) Cascade	5	56.7×	7e-07
Toll Like Receptor 5 (TLR5) Cascade	5	56.7×	7e-07
MyD88 cascade initiated on plasma membrane	5	53.7×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein phosphorylation	5	13.6×	6e-04
intracellular signal transduction	7	10.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

948 predictions. Top by Δscore:

Variant	Effect	Δscore
X:153648299:G:GT	donor_gain	1.0000
X:153648325:GG:G	donor_gain	1.0000
X:153648326:GG:G	donor_gain	1.0000
X:153648327:G:GG	donor_gain	1.0000
X:153648327:G:T	donor_gain	1.0000
X:153649672:GCCAT:G	donor_gain	1.0000
X:153649685:TTG:T	donor_gain	1.0000
X:153649687:GGTG:G	donor_loss	1.0000
X:153649688:G:GG	donor_gain	1.0000
X:153649688:GTGA:G	donor_loss	1.0000
X:153649689:T:A	donor_loss	1.0000
X:153650092:C:CA	acceptor_gain	1.0000
X:153642608:GGAG:G	donor_gain	0.9900
X:153642609:GAG:G	donor_gain	0.9900
X:153642609:GAGG:G	donor_gain	0.9900
X:153642609:GAGGT:G	donor_loss	0.9900
X:153642610:AGG:A	donor_loss	0.9900
X:153642611:GGT:G	donor_loss	0.9900
X:153642612:G:GG	donor_gain	0.9900
X:153642612:GT:G	donor_loss	0.9900
X:153642613:T:G	donor_loss	0.9900
X:153647917:A:AG	acceptor_gain	0.9900
X:153647918:G:GA	acceptor_gain	0.9900
X:153647918:GC:G	acceptor_gain	0.9900
X:153647918:GCGC:G	acceptor_gain	0.9900
X:153648300:A:T	donor_gain	0.9900
X:153648324:AGG:A	donor_gain	0.9900
X:153648324:AGGGT:A	donor_gain	0.9900
X:153648325:GGG:G	donor_gain	0.9900
X:153649686:TG:T	donor_gain	0.9900

AlphaMissense

2455 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:153649634:A:T	D259V	1.000
X:153650013:T:A	V288D	1.000
X:153650018:T:C	C290R	1.000
X:153650020:C:G	C290W	1.000
X:153650033:A:C	S295R	1.000
X:153650035:C:A	S295R	1.000
X:153650035:C:G	S295R	1.000
X:153650049:T:A	V300D	1.000
X:153650109:T:A	V320D	1.000
X:153650147:T:C	F333L	1.000
X:153650149:C:A	F333L	1.000
X:153650149:C:G	F333L	1.000
X:153650160:T:C	L337S	1.000
X:153649247:T:C	F130S	0.999
X:153649478:T:C	I207T	0.999
X:153649490:T:C	L211P	0.999
X:153649492:T:G	Y212D	0.999
X:153649559:T:A	L234H	0.999
X:153649559:T:C	L234P	0.999
X:153649563:T:A	N235K	0.999
X:153649563:T:G	N235K	0.999
X:153649622:T:C	I255T	0.999
X:153649633:G:C	D259H	0.999
X:153649634:A:C	D259A	0.999
X:153649634:A:G	D259G	0.999
X:153649681:T:C	F275L	0.999
X:153649682:T:C	F275S	0.999
X:153649683:C:A	F275L	0.999
X:153649683:C:G	F275L	0.999
X:153650010:T:C	L287P	0.999

dbSNP variants (sampled 300 via entrez): RS1000330198 (X:153645959 G>A), RS1001368058 (X:153647691 T>A), RS1003357550 (X:153650717 C>G), RS1003370947 (X:153641341 G>A,C,T), RS1003388589 (X:153650528 G>A,C), RS1003665888 (X:153641587 C>T), RS1003997716 (X:153642155 C>T), RS1004254132 (X:153650563 G>A), RS1005001418 (X:153644560 G>T), RS1005032971 (X:153643438 C>G), RS1005672666 (X:153640540 C>T), RS1006339634 (X:153648802 G>T), RS1006549746 (X:153645042 C>T), RS1006993103 (X:153644693 C>T), RS1007581452 (X:153646604 G>A)

Disease associations

OMIM: gene MIM:300134 | disease phenotypes: MIM:300908, MIM:127550

GenCC curated gene-disease

Mondo (2): anemia, nonspherocytic hemolytic, due to G6PD deficiency (MONDO:0010480), dyskeratosis congenita (MONDO:0015780)

Orphanet (2): Dyskeratosis congenita (Orphanet:1775), Class I glucose-6-phosphate dehydrogenase deficiency (Orphanet:466026)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000712_5	Type 2 diabetes	3.000000e-10
GCST001666_8	Type 2 diabetes	7.000000e-16
GCST002128_13	Type 2 diabetes	2.000000e-12
GCST004904_13	Body mass index	1.000000e-11
GCST005984_22	Glomerular filtration rate	1.000000e-11
GCST005985_12	Creatinine levels	1.000000e-10
GCST006001_6	Hemoglobin A1c levels	3.000000e-13
GCST007847_32	Type 2 diabetes	9.000000e-58
GCST007876_37	Estimated glomerular filtration rate	6.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004541	HbA1c measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D019871	Dyskeratosis Congenita	C15.378.190.223.500.750; C16.131.831.150; C16.320.322.108; C16.320.850.235; C17.800.804.150; C17.800.827.235
C567533	Anemia, Nonspherocytic Hemolytic, Due To G6pd Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	3
Estradiol	affects cotreatment, decreases expression	3
Copper	affects binding, decreases expression	2
Cyclosporine	decreases expression	2
FR900359	decreases phosphorylation	1
methyleugenol	decreases expression	1
bisphenol A	decreases expression	1
deoxynivalenol	decreases expression	1
glycidyl methacrylate	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	decreases expression	1
candoxin	decreases expression	1
belinostat	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Gefitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT01659606	PHASE2	ACTIVE_NOT_RECRUITING	Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
NCT03579875	PHASE2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT04232085	PHASE2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT04638517	PHASE2	TERMINATED	The TELO-SCOPE Study: Attenuating Telomere Attrition With Danazol. Is There Scope to Dramatically Improve Health Outcomes for Adults and Children With Pulmonary Fibrosis
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT06477614	PHASE1	RECRUITING	Anti-cancer DC Cell Vaccination to Treat Solid Tumors
NCT06817590	PHASE1	RECRUITING	Nucleoside Therapy in Patients With Telomere Biology Disorders
NCT00455312	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant (SCT) for Dyskeratosis Congenita or SAA
NCT01001598	PHASE1/PHASE2	TERMINATED	Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
NCT00027274	Not specified	RECRUITING	Cancer in Inherited Bone Marrow Failure Syndromes
NCT00499070	Not specified	COMPLETED	Assessing Immune Function in Young Patients With Cytopenia That Did Not Respond to Treatment
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT02162420	Not specified	COMPLETED	Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT04959188	Not specified	COMPLETED	Needs Assessment for Individuals and Families Affected by Dyskeratosis Congenita (DC) and Related Telomere Biology Disorders (TBD)
NCT06731036	Not specified	AVAILABLE	Expanded Access to CD34+ Selection Utilizing Miltenyi CliniMACS Prodigy® for Patients Receiving Peripheral Blood Stem Cell Transplantations and Stem Cell Boosts