DCPH1

Summary

DCPH1 (damage control phosphatase 1, HGNC:17872) is a protein-coding gene on chromosome 6q25.1, encoding Damage-control phosphatase 1 (Q9H993). Metal-dependent phosphatase that shows phosphatase activity against several substrates, including fructose-1-phosphate and fructose-6-phosphate.

Enables S-adenosylmethionine-dependent methyltransferase activity; enzyme binding activity; and protein carboxyl O-methyltransferase activity. Involved in DNA damage response.

Source: NCBI Gene 79624 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_024573

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17872
Approved symbol	DCPH1
Name	damage control phosphatase 1
Location	6q25.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12910
Ensembl gene	ENSG00000146476
Ensembl biotype	protein_coding
OMIM	616332
Entrez	79624

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000367294, ENST00000483931, ENST00000494826, ENST00000545879, ENST00000852534, ENST00000852535

RefSeq mRNA: 2 — MANE Select: NM_024573 NM_001286562, NM_024573

CCDS: CCDS5233, CCDS69224

Canonical transcript exons

ENST00000367294 — 5 exons

Exon	Start	End
ENSE00001023339	151452466	151452586
ENSE00001444086	151468343	151470101
ENSE00003536924	151458328	151458572
ENSE00003624781	151454548	151454653
ENSE00003650367	151464453	151464618

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 94.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.2505 / max 883.7888, expressed in 1789 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70606	31.2505	1789

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	94.48	gold quality
endometrium	UBERON:0001295	94.11	gold quality
palpebral conjunctiva	UBERON:0001812	94.04	gold quality
germinal epithelium of ovary	UBERON:0001304	94.02	gold quality
jejunal mucosa	UBERON:0000399	93.86	gold quality
lower lobe of lung	UBERON:0008949	93.44	gold quality
amniotic fluid	UBERON:0000173	93.20	gold quality
visceral pleura	UBERON:0002401	92.57	gold quality
decidua	UBERON:0002450	92.43	gold quality
pigmented layer of retina	UBERON:0001782	92.37	gold quality
nephron tubule	UBERON:0001231	91.73	gold quality
epithelium of nasopharynx	UBERON:0001951	91.73	gold quality
jejunum	UBERON:0002115	91.64	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.64	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.36	gold quality
colonic mucosa	UBERON:0000317	91.35	gold quality
parietal pleura	UBERON:0002400	91.32	gold quality
tibia	UBERON:0000979	91.06	gold quality
pleura	UBERON:0000977	90.95	gold quality
biceps brachii	UBERON:0001507	90.95	gold quality
superficial temporal artery	UBERON:0001614	90.16	gold quality
monocyte	CL:0000576	90.07	gold quality
calcaneal tendon	UBERON:0003701	89.92	gold quality
mononuclear cell	CL:0000842	89.91	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.87	gold quality
esophagus squamous epithelium	UBERON:0006920	89.74	gold quality
placenta	UBERON:0001987	89.73	gold quality
leukocyte	CL:0000738	89.60	gold quality
adrenal tissue	UBERON:0018303	89.42	gold quality
mammary duct	UBERON:0001765	89.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	3035.49
E-GEOD-100618	yes	546.93
E-MTAB-9388	yes	10.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting DCPH1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
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-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
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-1250-3P	99.96	70.04	4038
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839

Literature-anchored findings (GeneRIF, showing 4)

• C6ORF211 correlates with proliferation and clinical outcome in tumors. (PMID:21552322)
• Armt1 protein specifically targets proliferating cell nuclear antigen (PCNA) in breast cancer cells, predominately methylating glutamate side chains. (PMID:25732820)
• Studies show that acidic residue methyltransferase 1 (Armt1) has a vital role in regulation of the DNA damage response likely through its ability to O-methylate glutamyl residues of the DNA repair factor proliferating cell nuclear antigen (PCNA). (PMID:26450907)
• Human ARMT1 structure and substrate specificity indicates that it is a DUF89 family damage-control phosphatase. (PMID:32682077)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	armt1	ENSDARG00000055676
mus_musculus	Armt1	ENSMUSG00000061759
rattus_norvegicus	Armt1	ENSRNOG00000019489
drosophila_melanogaster	CG4161	FBGN0028892
drosophila_melanogaster	CG11475	FBGN0034687
drosophila_melanogaster	CG11474	FBGN0034688
drosophila_melanogaster	CG2921	FBGN0034689
caenorhabditis_elegans		WBGENE00009290

Protein

Protein identifiers

Damage-control phosphatase 1 — Q9H993 (reviewed: Q9H993)

Alternative names: Acidic residue methyltransferase 1, Damage-control phosphatase ARMT1, Damage-control phosphatase DUF89, Protein-glutamate O-methyltransferase, Sugar phosphate phosphatase DCPH1

All UniProt accessions (3): Q9H993, F2Z3I8, F5GZY1

UniProt curated annotations — full annotation on UniProt →

Function. Metal-dependent phosphatase that shows phosphatase activity against several substrates, including fructose-1-phosphate and fructose-6-phosphate. Its preference for fructose-1-phosphate, a strong glycating agent that causes DNA damage rather than a canonical yeast metabolite, suggests a damage-control function in hexose phosphate metabolism. Has also been shown to have O-methyltransferase activity that methylates glutamate residues of target proteins to form gamma-glutamyl methyl ester residues. Possibly methylates PCNA, suggesting it is involved in the DNA damage response.

Post-translational modifications. Automethylated.

Cofactor. Phosphatase activity is strongly promoted by several divalent cations but higher catalytic efficiency has been shown in presnce of Co(2+) compared to Mg(2+).

Domain organisation. Subfamily III proteins have a conserved RTxK motif about 40-50 residues from the C-terminus; the threonine may be replaced by serine or cysteine.

Similarity. Belongs to the damage-control phosphatase family. Sugar phosphate phosphatase III subfamily.

RefSeq proteins (2): NP_001273491, NP_078849* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002791	ARMT1-like_metal-bd	Domain
IPR036075	ARMT-1-like_metal-bd_sf	Homologous_superfamily
IPR039763	ARMT1	Family

Pfam: PF01937

Catalyzed reactions (Rhea), 3 shown:

• L-glutamyl-[protein] + S-adenosyl-L-methionine = [protein]-L-glutamate 5-O-methyl ester + S-adenosyl-L-homocysteine (RHEA:24452)
• beta-D-fructose 6-phosphate = dihydroxyacetone + D-glyceraldehyde 3-phosphate (RHEA:28002)
• beta-D-fructose 1-phosphate + H2O = D-fructose + phosphate (RHEA:35603)

UniProt features (66 total): helix 24, binding site 11, strand 8, sequence variant 7, turn 5, sequence conflict 4, modified residue 3, initiator methionine 1, chain 1, short sequence motif 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6UMQ	X-RAY DIFFRACTION	1.85
6UMR	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H993-F1	95.36	0.94

Functional residue map

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

Ligand- & substrate-binding residues (11): 291; 291; 367–371; 404; 253–254; 253; 253; 254; 254; 258; 291

Post-translational modifications (3): 2, 40, 102

Mutagenesis-validated functional residues (1):

Position	Phenotype
291	no mn(2+)-binding. loss of phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): MODULE_151, YANG_BREAST_CANCER_ESR1_BULK_UP, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, chr6q25, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, SMID_BREAST_CANCER_LUMINAL_B_UP, USF_01, GOBP_DNA_DAMAGE_RESPONSE, AACTTT_UNKNOWN, HAHTOLA_SEZARY_SYNDROM_UP, USF_02, GOBP_METHYLATION, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, XU_GH1_AUTOCRINE_TARGETS_DN

GO Biological Process (2): DNA damage response (GO:0006974), methylation (GO:0032259)

GO Molecular Function (12): S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), phosphatase activity (GO:0016791), enzyme binding (GO:0019899), metal ion binding (GO:0046872), protein carboxyl O-methyltransferase activity (GO:0051998), fructose 6-phosphate aldolase activity (GO:0097023), fructose-1-phosphatase activity (GO:0103026), protein binding (GO:0005515), methyltransferase activity (GO:0008168), protein-glutamate O-methyltransferase activity (GO:0008983), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
cellular response to stress	1
metabolic process	1
methyltransferase activity	1
phosphoric ester hydrolase activity	1
protein binding	1
cation binding	1
protein methyltransferase activity	1
carboxyl-O-methyltransferase activity	1
aldehyde-lyase activity	1
phosphatase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
S-adenosylmethionine-dependent methyltransferase activity	1
protein carboxyl O-methyltransferase activity	1

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCPH1	CCDC170	Q8IYT3	788
DCPH1	RMND1	Q9NWS8	788
DCPH1	ZBTB2	Q8N680	633
DCPH1	PANK4	Q9NVE7	558
DCPH1	PLEKHG1	Q9ULL1	472
DCPH1	AKAP12	Q02952	418
DCPH1	PARD6B	Q9BYG5	405
DCPH1	SYNE1	Q8NF91	401
DCPH1	MTHFD1L	Q6UB35	394
DCPH1	MAX	P25912	372
DCPH1	ESR1	P03372	370
DCPH1	ETV7	Q9Y603	346
DCPH1	LRRC41	Q15345	345
DCPH1	NSMCE4A	Q9NXX6	340
DCPH1	INTS7	Q9NVH2	330

IntAct

61 interactions, top by confidence:

A	B	Type	Score
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
PPP3CA	ARMT1	psi-mi:“MI:0915”(physical association)	0.670
RCAN1	PPP3CB	psi-mi:“MI:0914”(association)	0.660
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
ARMT1	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
LRRK2		psi-mi:“MI:0914”(association)	0.350
FAM153B	FAM153A	psi-mi:“MI:0914”(association)	0.350
FGB	NME2	psi-mi:“MI:0914”(association)	0.350
RWDD2B	DENR	psi-mi:“MI:0914”(association)	0.350
RCAN3	OBSL1	psi-mi:“MI:0914”(association)	0.350
RCAN2	HSBP1	psi-mi:“MI:0914”(association)	0.350
RCAN1	CLEC3A	psi-mi:“MI:0914”(association)	0.350
NKD2	YWHAB	psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
PPP3CA	RCAN1	psi-mi:“MI:0914”(association)	0.350
PPP3CB	PI4KA	psi-mi:“MI:0914”(association)	0.350
FGB	KIF2A	psi-mi:“MI:0914”(association)	0.350
NKD2	YWHAQ	psi-mi:“MI:0914”(association)	0.350
RWDD2B	CMPK1	psi-mi:“MI:0914”(association)	0.350
UGT1A3	SERPINB8	psi-mi:“MI:0914”(association)	0.350
GP1BB	RHOA	psi-mi:“MI:0914”(association)	0.350

BioGRID (85): C6orf211 (Affinity Capture-MS), C6orf211 (Affinity Capture-MS), C6orf211 (Affinity Capture-MS), C6orf211 (Affinity Capture-MS), C6orf211 (Affinity Capture-MS), C6orf211 (Two-hybrid), APIP (Co-fractionation), C6orf211 (Co-fractionation), C6orf211 (Co-fractionation), C6orf211 (Co-fractionation), C6orf211 (Co-fractionation), C6orf211 (Co-fractionation), C6orf211 (Co-fractionation), C6orf211 (Co-fractionation), C6orf211 (Co-fractionation)

ESM2 similar proteins: A0AVT1, A1L1C5, A1L259, A2RTX5, A3KMX8, A5PJD0, A6H630, A6NGE7, B8ZXI1, O60678, O70467, O75879, P32455, P32456, Q0V9S0, Q0ZDF7, Q22017, Q283N4, Q2KHV5, Q4R526, Q4R646, Q58EM4, Q5D1D6, Q5R998, Q5RBE1, Q5ZIE6, Q61107, Q68EH8, Q6AXB1, Q6AYT5, Q6DJ95, Q6DJA3, Q6ING7, Q6NTW6, Q6PA41, Q6ZN66, Q7SXP2, Q7T010, Q8BIJ6, Q8BLY2

Diamond homologs: A3KMX8, A6H630, O94725, Q04371, Q4R526, Q58EM4, Q6AXB1, Q6AYT5, Q6DJA3, Q8MMH3, Q9H993, Q9UT55

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

887 predictions. Top by Δscore:

Variant	Effect	Δscore
6:151452540:A:T	donor_gain	1.0000
6:151452579:G:GT	donor_gain	1.0000
6:151458323:TGCA:T	acceptor_loss	1.0000
6:151458325:CA:C	acceptor_loss	1.0000
6:151458326:A:T	acceptor_loss	1.0000
6:151458327:GGAA:G	acceptor_gain	1.0000
6:151464446:A:AG	acceptor_gain	1.0000
6:151464447:C:G	acceptor_gain	1.0000
6:151464451:A:AG	acceptor_gain	1.0000
6:151464452:G:GG	acceptor_gain	1.0000
6:151464452:GTCC:G	acceptor_gain	1.0000
6:151464596:A:G	donor_gain	1.0000
6:151464614:TGCAG:T	donor_loss	1.0000
6:151464615:GCAGG:G	donor_loss	1.0000
6:151464617:AGG:A	donor_loss	1.0000
6:151464618:GG:G	donor_loss	1.0000
6:151464620:T:G	donor_loss	1.0000
6:151452574:G:GT	donor_gain	0.9900
6:151452575:A:T	donor_gain	0.9900
6:151452582:GTGGG:G	donor_gain	0.9900
6:151452583:TGGGG:T	donor_loss	0.9900
6:151452584:GGG:G	donor_gain	0.9900
6:151452584:GGGGT:G	donor_loss	0.9900
6:151452585:GG:G	donor_gain	0.9900
6:151452585:GGG:G	donor_gain	0.9900
6:151452586:GG:G	donor_gain	0.9900
6:151452587:G:GG	donor_gain	0.9900
6:151452587:GTTA:G	donor_loss	0.9900
6:151458326:A:AG	acceptor_gain	0.9900
6:151458326:AG:A	acceptor_gain	0.9900

AlphaMissense

2911 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:151458545:G:C	R122P	0.994
6:151458377:G:C	R66P	0.992
6:151468632:A:T	K283I	0.991
6:151468896:G:C	R371T	0.991
6:151468995:A:T	K404I	0.991
6:151468897:G:C	R371S	0.990
6:151468897:G:T	R371S	0.990
6:151468896:G:T	R371M	0.989
6:151464492:A:C	K144N	0.988
6:151464492:A:T	K144N	0.988
6:151458502:T:A	W108R	0.987
6:151458502:T:C	W108R	0.987
6:151464478:T:C	F140L	0.987
6:151464480:T:A	F140L	0.987
6:151464480:T:G	F140L	0.987
6:151468879:G:C	K365N	0.987
6:151468879:G:T	K365N	0.987
6:151454619:G:C	R38P	0.986
6:151468646:T:C	F288L	0.986
6:151468648:T:A	F288L	0.986
6:151468648:T:G	F288L	0.986
6:151464491:A:T	K144I	0.985
6:151468643:T:A	W287R	0.985
6:151468643:T:C	W287R	0.985
6:151468542:A:T	D253V	0.984
6:151468996:A:C	K404N	0.983
6:151468996:A:T	K404N	0.983
6:151468790:T:A	W336R	0.982
6:151468790:T:C	W336R	0.982
6:151468881:G:T	G366V	0.982

dbSNP variants (sampled 300 via entrez): RS1000014192 (6:151461229 T>C), RS1000066432 (6:151461587 C>T), RS1000180898 (6:151458153 G>A), RS1000286355 (6:151452337 T>C,G), RS1000298143 (6:151450887 A>G), RS1000334305 (6:151452481 C>A,T), RS1000620560 (6:151451571 C>T), RS1000672835 (6:151451783 A>G,T), RS1000919771 (6:151456922 A>G), RS1000927184 (6:151467341 A>G), RS1001032665 (6:151462851 T>C), RS1001137822 (6:151456573 G>T), RS1001519653 (6:151452800 C>G,T), RS1001637289 (6:151451639 C>T), RS1001743686 (6:151462815 G>A,T)

Disease associations

OMIM: gene MIM:616332 | 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
GCST001063_1	Chronic myeloid leukemia	2.000000e-06
GCST004735_17	Epstein-Barr virus copy number in lymphoblastoid cell lines	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression, affects expression	4
perfluorooctane sulfonic acid	decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benztropine	increases expression	1
Cisplatin	increases expression	1
Clozapine	increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Nickel	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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