MDP1

Summary

MDP1 (magnesium dependent phosphatase 1, HGNC:28781) is a protein-coding gene on chromosome 14q12, encoding Magnesium-dependent phosphatase 1 (Q86V88). Magnesium-dependent phosphatase which may act as a tyrosine phosphatase.

Predicted to enable acid phosphatase activity. Predicted to be involved in chromatin remodeling.

Source: NCBI Gene 145553 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_138476

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28781
Approved symbol	MDP1
Name	magnesium dependent phosphatase 1
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	MGC5987, FN6Pase
Ensembl gene	ENSG00000213920
Ensembl biotype	protein_coding
Entrez	145553

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 retained_intron, 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000288087, ENST00000396833, ENST00000466422, ENST00000525696, ENST00000528849, ENST00000530222, ENST00000531553, ENST00000532557, ENST00000532742, ENST00000533536, ENST00000915890, ENST00000915891, ENST00000915892

RefSeq mRNA: 4 — MANE Select: NM_138476 NM_001199821, NM_001199822, NM_001412188, NM_138476

CCDS: CCDS55908, CCDS9620

Canonical transcript exons

ENST00000288087 — 6 exons

Exon	Start	End
ENSE00001712726	24213943	24214151
ENSE00001814413	24215919	24216066
ENSE00003507955	24214310	24214395
ENSE00003553983	24215552	24215662
ENSE00003558937	24215737	24215797
ENSE00003593450	24214492	24214599

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 94.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6824 / max 108.2100, expressed in 1795 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142554	5.6670	1734
142552	3.5584	1437
142553	3.4570	1509

Top tissues by expression

138 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	94.73	gold quality
prefrontal cortex	UBERON:0000451	91.81	gold quality
adenohypophysis	UBERON:0002196	90.70	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.70	gold quality
frontal cortex	UBERON:0001870	90.68	gold quality
frontal lobe	UBERON:0016525	90.68	gold quality
pituitary gland	UBERON:0000007	90.66	gold quality
substantia nigra	UBERON:0002038	90.35	gold quality
amygdala	UBERON:0001876	90.32	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.32	gold quality
temporal lobe	UBERON:0001871	90.25	gold quality
putamen	UBERON:0001874	90.06	gold quality
anterior cingulate cortex	UBERON:0009835	90.02	gold quality
hypothalamus	UBERON:0001898	89.99	gold quality
nucleus accumbens	UBERON:0001882	89.97	gold quality
cerebral cortex	UBERON:0000956	89.94	gold quality
left coronary artery	UBERON:0001626	89.84	gold quality
calcaneal tendon	UBERON:0003701	89.81	gold quality
descending thoracic aorta	UBERON:0002345	89.78	gold quality
thoracic aorta	UBERON:0001515	89.73	gold quality
ascending aorta	UBERON:0001496	89.68	gold quality
right adrenal gland	UBERON:0001233	89.52	gold quality
right frontal lobe	UBERON:0002810	89.52	gold quality
brain	UBERON:0000955	89.42	gold quality
Ammon’s horn	UBERON:0001954	89.30	gold quality
right coronary artery	UBERON:0001625	89.27	gold quality
left adrenal gland cortex	UBERON:0035825	89.08	gold quality
right adrenal gland cortex	UBERON:0035827	88.95	gold quality
left adrenal gland	UBERON:0001234	88.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.16

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• We showed that down-regulation of MDP-1 expression was correlated with poorly differentiated carcinoma and later tumor stage, and it predicted a significantly poorer disease-free survival. (PMID:28678323)
• Magnesium-dependent Phosphatase (MDP) 1 is a Potential Suppressor of Gastric Cancer. (PMID:31218958)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Magnesium-dependent phosphatase 1 — Q86V88 (reviewed: Q86V88)

All UniProt accessions (1): Q86V88

UniProt curated annotations — full annotation on UniProt →

Function. Magnesium-dependent phosphatase which may act as a tyrosine phosphatase.

Activity regulation. Inhibited by vanadate and zinc, and slightly by calcium.

Similarity. Belongs to the HAD-like hydrolase superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86V88-1	1	yes
Q86V88-2	2
Q86V88-3	3

RefSeq proteins (4): NP_001186750, NP_001186751, NP_001399117, NP_612485* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010033	HAD_SF_ppase_IIIC	Domain
IPR010036	MDP_1_eu_arc	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR035679	MDP-1_euk	Family
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF12689

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (34 total): binding site 10, strand 7, helix 6, splice variant 4, turn 4, active site 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2WM8	X-RAY DIFFRACTION	1.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86V88-F1	93.88	0.91

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 (2): 11 (nucleophile); 13 (proton donor)

Ligand- & substrate-binding residues (10): 70; 100; 123; 11; 12; 13; 13; 20; 69; 70

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, chr14q12, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, IK3_01, CART1_01, SENESE_HDAC3_TARGETS_DN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, GOMF_PROTEIN_TYROSINE_PHOSPHATASE_ACTIVITY, WANG_TUMOR_INVASIVENESS_UP, GOMF_ACID_PHOSPHATASE_ACTIVITY, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_UP, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, STAT6_01

GO Biological Process (0):

GO Molecular Function (6): acid phosphatase activity (GO:0003993), protein tyrosine phosphatase activity (GO:0004725), metal ion binding (GO:0046872), phosphoprotein phosphatase activity (GO:0004721), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatase activity	2
phosphoprotein phosphatase activity	1
cation binding	1
catalytic activity, acting on a protein	1
catalytic activity	1
phosphoric ester hydrolase activity	1

Protein interactions and networks

STRING

138 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MDP1	CLRN3	Q8NCR9	476
MDP1	ITPRIP	Q8IWB1	445
MDP1	FN3K	Q9H479	395
MDP1	GRIP2	Q9C0E4	381
MDP1	ZNF207	O43670	366
MDP1	USP21	Q9UK80	349
MDP1	ETV3	P41162	345
MDP1	SYNGR1	O43759	331
MDP1	ZNF518A	Q6AHZ1	330
MDP1	ISLR	O14498	321
MDP1	PSMD6	Q15008	310
MDP1	CASP8AP2	Q9UKL3	305
MDP1	PSMD7	P51665	285
MDP1	HEATR5B	Q9P2D3	270
MDP1	HOXC4	P09017	265

IntAct

7 interactions, top by confidence:

A	B	Type	Score
ANAPC10	MDP1	psi-mi:“MI:0915”(physical association)	0.400
MDP1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
SH2D1A	MDP1	psi-mi:“MI:0914”(association)	0.350
MDP1	VSIG8	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350

BioGRID (54): ACOT7 (Affinity Capture-MS), ACTN4 (Affinity Capture-MS), CARM1 (Affinity Capture-MS), CCT5 (Affinity Capture-MS), COPG1 (Affinity Capture-MS), CPNE3 (Affinity Capture-MS), DNM1L (Affinity Capture-MS), DPYSL2 (Affinity Capture-MS), DPYSL5 (Affinity Capture-MS), EEF1B2 (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), FKBP15 (Affinity Capture-MS), FLAD1 (Affinity Capture-MS), FLNA (Affinity Capture-MS), FLNB (Affinity Capture-MS)

ESM2 similar proteins: A0A0K9RL25, A0A0U1WZ18, A0A1S4A695, B9N1F9, E0CSI1, O15305, O35331, O35621, O80840, P78330, Q08DP0, Q16HW7, Q1W374, Q1W375, Q1W376, Q1W377, Q259G4, Q29NT9, Q2KHU0, Q2R483, Q3SZJ9, Q3UFY7, Q5E982, Q5I0K3, Q5M819, Q5RB83, Q5RFI8, Q5ZID6, Q5ZKF6, Q5ZMA6, Q60HD6, Q6AYP7, Q7SYN4, Q7TSV4, Q7XPW5, Q86V88, Q8GWU0, Q8K183, Q8N0X4, Q8R4N0

Diamond homologs: O94279, P40081, Q86V88, Q9D967

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

782 predictions. Top by Δscore:

Variant	Effect	Δscore
14:24214264:AATC:A	donor_gain	1.0000
14:24214293:T:TA	donor_gain	1.0000
14:24214305:AGTAC:A	donor_gain	1.0000
14:24214595:TTGTC:T	acceptor_gain	1.0000
14:24214596:TGTC:T	acceptor_gain	1.0000
14:24214597:GTC:G	acceptor_gain	1.0000
14:24214598:TC:T	acceptor_gain	1.0000
14:24214598:TCC:T	acceptor_loss	1.0000
14:24214599:CC:C	acceptor_gain	1.0000
14:24214600:C:CA	acceptor_loss	1.0000
14:24214600:C:CC	acceptor_gain	1.0000
14:24214600:CTGCA:C	acceptor_loss	1.0000
14:24214601:T:C	acceptor_loss	1.0000
14:24214608:CGG:C	acceptor_gain	1.0000
14:24214610:G:C	acceptor_gain	1.0000
14:24214610:G:GC	acceptor_gain	1.0000
14:24215661:CA:C	acceptor_gain	1.0000
14:24215663:C:CC	acceptor_gain	1.0000
14:24214149:CAC:C	acceptor_gain	0.9900
14:24214152:C:CC	acceptor_gain	0.9900
14:24214153:T:A	acceptor_loss	0.9900
14:24214486:GCATA:G	donor_loss	0.9900
14:24214487:CATAC:C	donor_loss	0.9900
14:24214491:CC:C	donor_loss	0.9900
14:24214603:C:CT	acceptor_gain	0.9900
14:24214604:A:T	acceptor_gain	0.9900
14:24214609:G:T	acceptor_gain	0.9900
14:24214612:G:C	acceptor_gain	0.9900
14:24215547:CTTA:C	donor_loss	0.9900
14:24215548:TTACC:T	donor_loss	0.9900

AlphaMissense

1160 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:24214509:C:A	K100N	0.989
14:24214509:C:G	K100N	0.989
14:24215786:A:G	W17R	0.988
14:24215786:A:T	W17R	0.988
14:24215796:A:C	D13E	0.983
14:24215796:A:T	D13E	0.983
14:24215797:T:A	D13V	0.981
14:24214511:T:G	K100Q	0.980
14:24215924:T:A	D11V	0.979
14:24214347:A:C	D122E	0.978
14:24214347:A:T	D122E	0.978
14:24214510:T:A	K100M	0.978
14:24214332:A:C	N127K	0.977
14:24214332:A:T	N127K	0.977
14:24214510:T:G	K100T	0.976
14:24215558:G:T	A68D	0.976
14:24215784:C:A	W17C	0.976
14:24215784:C:G	W17C	0.976
14:24215923:A:C	D11E	0.976
14:24215923:A:T	D11E	0.976
14:24215919:C:G	D13H	0.974
14:24214353:G:C	F120L	0.973
14:24214353:G:T	F120L	0.973
14:24214355:A:G	F120L	0.973
14:24214084:A:C	F157L	0.972
14:24214084:A:T	F157L	0.972
14:24214086:A:G	F157L	0.972
14:24215924:T:G	D11A	0.972
14:24214344:A:C	D123E	0.971
14:24214344:A:T	D123E	0.971

dbSNP variants (sampled 300 via entrez): RS1000169072 (14:24213821 G>A,T), RS1000408551 (14:24218000 G>C,T), RS1003518970 (14:24216851 G>C), RS1004641002 (14:24217922 A>C), RS1004755206 (14:24213468 C>G,T), RS1005354008 (14:24215212 A>G), RS1005833595 (14:24217409 C>T), RS1007736547 (14:24216006 T>G), RS1007813063 (14:24216288 G>A), RS1008217639 (14:24216072 G>A,C,T), RS1008740393 (14:24217481 G>A,C,T), RS1008762507 (14:24217321 G>A), RS1008772370 (14:24217493 T>A), RS1010307288 (14:24213879 T>C), RS1010559259 (14:24215188 C>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	decreases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Valproic Acid	decreases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer