PHPT1

Summary

PHPT1 (phosphohistidine phosphatase 1, HGNC:30033) is a protein-coding gene on chromosome 9q34.3, encoding 14 kDa phosphohistidine phosphatase (Q9NRX4). Exhibits phosphohistidine phosphatase activity.

This gene encodes an enzyme that catalyzes the reversible dephosphorylation of histidine residues in proteins. It may be involved in the dephosphorylation of G-beta and ATP citrate lyase and in negatively regulating CD4 T lymphocytes by dephosphorylation and inhibition of KCa3.1 channels. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 29085 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014172

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30033
Approved symbol	PHPT1
Name	phosphohistidine phosphatase 1
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	PHP14, HSPC141, CGI-202, DKFZp564M173, bA216L13.10
Ensembl gene	ENSG00000054148
Ensembl biotype	protein_coding
OMIM	610167
Entrez	29085

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000247665, ENST00000371661, ENST00000462205, ENST00000463215, ENST00000492540, ENST00000497413, ENST00000929909, ENST00000929910

RefSeq mRNA: 4 — MANE Select: NM_014172 NM_001135861, NM_001287342, NM_001287343, NM_014172

CCDS: CCDS48060, CCDS7009

Canonical transcript exons

ENST00000247665 — 3 exons

Exon	Start	End
ENSE00001888328	136849409	136849590
ENSE00003612613	136850755	136851024
ENSE00003724754	136850013	136850137

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 99.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.1769 / max 406.3401, expressed in 1818 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99569	36.9383	1814
99570	3.8423	1336
99573	3.0441	1080
99567	1.5737	896
99568	1.0197	778
99571	0.5013	232
99572	0.2575	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.03	gold quality
adenohypophysis	UBERON:0002196	99.02	gold quality
right adrenal gland	UBERON:0001233	98.83	gold quality
right adrenal gland cortex	UBERON:0035827	98.82	gold quality
right atrium auricular region	UBERON:0006631	98.76	gold quality
body of pancreas	UBERON:0001150	98.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.70	gold quality
left adrenal gland cortex	UBERON:0035825	98.70	gold quality
left adrenal gland	UBERON:0001234	98.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.66	gold quality
mucosa of transverse colon	UBERON:0004991	98.65	gold quality
right lobe of thyroid gland	UBERON:0001119	98.46	gold quality
right uterine tube	UBERON:0001302	98.45	gold quality
gastrocnemius	UBERON:0001388	98.43	gold quality
cerebellar hemisphere	UBERON:0002245	98.39	gold quality
left lobe of thyroid gland	UBERON:0001120	98.38	gold quality
right testis	UBERON:0004534	98.38	gold quality
anterior cingulate cortex	UBERON:0009835	98.35	gold quality
left testis	UBERON:0004533	98.32	gold quality
cerebellar cortex	UBERON:0002129	98.29	gold quality
right frontal lobe	UBERON:0002810	98.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.13	gold quality
metanephros cortex	UBERON:0010533	98.08	gold quality
left coronary artery	UBERON:0001626	97.98	gold quality
body of stomach	UBERON:0001161	97.96	gold quality
pancreatic ductal cell	CL:0002079	97.92	silver quality
heart left ventricle	UBERON:0002084	97.92	gold quality
ascending aorta	UBERON:0001496	97.91	gold quality
thoracic aorta	UBERON:0001515	97.91	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	38.50
E-CURD-112	yes	27.48
E-HCAD-1	yes	21.26
E-CURD-46	yes	10.92
E-MTAB-8271	yes	9.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting PHPT1, 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-6762-3P	99.66	66.94	1188
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302

Literature-anchored findings (GeneRIF, showing 20)

• Northern blot analysis indicated that the human phosphohistidine phosphatase mRNA was present preferentially in heart and skeletal muscle. (PMID:12383260)
• In the present work, we have searched for potential active site residues in the human phosphohistidine phosphatase by point mutations of conserved histidine and arginine residues to alanine. (PMID:16219293)
• Overexpression of PHP results in increased dephosphorylation with concomitant inactivation of ACL, thus finally leading to cell damage. (PMID:18656514)
• PHPT-1 functions to negatively regulate CD4 T cells (PMID:18796614)
• Solution structure and catalytic mechanism of human protein histidine phosphatase 1. (PMID:18991813)
• results suggest that an increased activity of protein histidine phosphatase (PHP) impairs neuron cellular function whereas downregulation of PHP does not (PMID:19138678)
• These results demonstrate for the first time that PHP14 may be functionally important in lung cancer cell migration and the invasion of lung cancer cells, mediated partly through modulation of actin cytoskeleton rearrangement. (PMID:19344975)
• these data implicate regulatory roles for PHPT1 in a G protein-sensitive step involved in nutrient-induced insulin secretion (PMID:20501872)
• Significantly higher expression levels of PHPT1 protein were found in lung cancer samples than in normal tissues adjacent to lung cancer. (PMID:21163124)
• Overexpression of PHP by the use of a plasmid vector, pIRES2-AcGFP1-PHP, induced apoptosis in HUVEC (PMID:21967643)
• the histidine phosphatase, protein histidine phosphatase 1, inhibits NDPK-B-activated TRPV5 in inside/out patch experiments. (PMID:24523290)
• The specific degradation of the PHPT1 splice variant indicates that the quality control and the self-guarding of the cellular system works at two levels, first at the RNA level and proteasome level. (PMID:25450458)
• PHPT1 can dephosphorylate phospholysine in chemically phosphorylated histone H1 and polylysine (PMID:25574816)
• PHPT1 was expressed in the epithelium of proximal tubuli and nuclei of clear-cell renal cell carcinoma tissue samples. (PMID:26537769)
• H2O2 exposure induces selective oxidation of hPHPT1 at Met95, a residue within the substrate binding region. Molecular dynamics simulations suggest that if Met95 oxidation alters hPHPT1 activity, then it will do so by altering the stability of an intermediate state. Mass spectrometry showed that H2O2-induced oxidation does not impact hPHPT1 function negatively. (PMID:27034094)
• Our study reveals the important role of PHP14 in regulating hepatic stellate cell migration in liver fibrosis (PMID:29098317)
• In the process of assay optimization, we discovered that PHPT1 is sensitive to a reducing environment and inhibited by transition-metal ions, with one apparent Cu(II) binding site with IC50 value of 500 +/- 20 muM and two apparent Zn(II) binding sites with IC50 values of 25 +/- 1 and 490 +/- 20 muM (PMID:29630837)
• High PHPT1 expression is associated with cancer. (PMID:29787434)
• FBXO32 targets PHPT1 for ubiquitination to regulate the growth of EGFR mutant lung cancer. (PMID:35411430)
• A salt bridge of the C-terminal carboxyl group regulates PHPT1 substrate affinity and catalytic activity. (PMID:38747379)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	phpt1	ENSDARG00000045567
mus_musculus	Phpt1	ENSMUSG00000036504
drosophila_melanogaster	janA	FBGN0001280
drosophila_melanogaster	janB	FBGN0001281
drosophila_melanogaster	CG18662	FBGN0040963
drosophila_melanogaster	ocn	FBGN0041102
caenorhabditis_elegans	phip-1	WBGENE00009455

Protein

Protein identifiers

14 kDa phosphohistidine phosphatase — Q9NRX4 (reviewed: Q9NRX4)

Alternative names: Phosphohistidine phosphatase 1, Protein histidine phosphatase, Protein janus-A homolog

All UniProt accessions (2): Q9NRX4, V9HWC4

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits phosphohistidine phosphatase activity.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed abundantly in heart and skeletal muscle.

Similarity. Belongs to the janus family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRX4-1	1	yes
Q9NRX4-2	2

RefSeq proteins (4): NP_001129333, NP_001274271, NP_001274272, NP_054891* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007702	Janus	Family
IPR038596	Janus_sf	Homologous_superfamily

Pfam: PF05005

Enzyme classification (BRENDA):

• EC 3.9.1.3 — phosphohistidine phosphatase (BRENDA: 10 organisms, 42 substrates, 23 inhibitors, 2 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYLPHOSPHATE	7.4	1
6,8-DIFLUOROMETHYLUMBELLIFERYL PHOSPHATE	0.22	1

Catalyzed reactions (Rhea), 2 shown:

• N(tele)-phospho-L-histidyl-[protein] + H2O = L-histidyl-[protein] + phosphate (RHEA:47960)
• N(pros)-phospho-L-histidyl-[protein] + H2O = L-histidyl-[protein] + phosphate (RHEA:47964)

UniProt features (28 total): mutagenesis site 6, strand 6, helix 4, sequence conflict 3, turn 2, binding site 2, initiator methionine 1, chain 1, active site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2HW4	X-RAY DIFFRACTION	1.9
2NMM	X-RAY DIFFRACTION	2.7
2AI6	SOLUTION NMR
2OZW	SOLUTION NMR
2OZX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRX4-F1	91.63	0.81

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): 53 (proton acceptor)

Ligand- & substrate-binding residues (2): 21; 94–96

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (6):

Position	Phenotype
78	decreased affinity for substrate and reduced catalytic activity.
94	decreased affinity for substrate and strongly reduced catalytic activity.
102	decreased affinity for substrate and slightly reduced catalytic activity.
21	decreased affinity for substrate and strongly reduced catalytic activity.
45	slightly decreased affinity for substrate, but no effect on catalytic activity.
53	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 235 (showing top): AHRARNT_01, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_POSITIVE_REGULATION_OF_INSULIN_SECRETION, GOBP_NEGATIVE_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (5): actin cytoskeleton organization (GO:0030036), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), negative regulation of T cell receptor signaling pathway (GO:0050860), lamellipodium organization (GO:0097581), positive regulation of cell motility (GO:2000147)

GO Molecular Function (8): enzyme inhibitor activity (GO:0004857), calcium channel inhibitor activity (GO:0019855), transmembrane transporter binding (GO:0044325), actin filament binding (GO:0051015), protein histidine phosphatase activity (GO:0101006), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear body (GO:0016604), leading edge of lamellipodium (GO:0061851), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
catalytic activity	2
cytoskeleton organization	1
actin filament-based process	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
plasma membrane bounded cell projection organization	1
positive regulation of locomotion	1
positive regulation of cellular process	1
cell motility	1
regulation of cell motility	1
enzyme regulator activity	1
molecular function inhibitor activity	1
calcium channel regulator activity	1
calcium channel activity	1
ion channel inhibitor activity	1
protein binding	1
actin binding	1
protein-containing complex binding	1
phosphoprotein phosphatase activity	1
hydrolase activity, acting on phosphorus-nitrogen bonds	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
nucleoplasm	1
intracellular membraneless organelle	1
lamellipodium	1
cell leading edge	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHPT1	NME2	P22392	781
PHPT1	KCNN4	O15554	751
PHPT1	LHPP	Q9H008	693
PHPT1	MTMR6	Q9Y217	655
PHPT1	ACLY	P53396	539
PHPT1	PGAM5	Q96HS1	519
PHPT1	TMEM141	Q96I45	508
PHPT1	FDXR	P22570	483
PHPT1	GADD45A	P24522	477
PHPT1	NME1	P15531	466
PHPT1	CCNG1	P51959	465
PHPT1	CDKN1A	P38936	461
PHPT1	ERG28	Q9UKR5	434
PHPT1	NAPG	Q99747	407
PHPT1	GDA	Q9Y2T3	402

IntAct

44 interactions, top by confidence:

A	B	Type	Score
ATXN1	PHPT1	psi-mi:“MI:0915”(physical association)	0.670
PHPT1	TPM4	psi-mi:“MI:0915”(physical association)	0.400
PHPT1	KCNN4	psi-mi:“MI:0915”(physical association)	0.400
KCNN4	PHPT1	psi-mi:“MI:0915”(physical association)	0.400
TINF2	PHPT1	psi-mi:“MI:0915”(physical association)	0.370
ERBB3	PHPT1	psi-mi:“MI:0915”(physical association)	0.370
PHPT1	DNMT3L	psi-mi:“MI:0915”(physical association)	0.370
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	KRAS	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350
GTF2E2	STX7	psi-mi:“MI:0914”(association)	0.350
DNAJB6	SCAMP1	psi-mi:“MI:0914”(association)	0.350
AZU1	UBA6	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
LGALS9	CYB5A	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
OAS1	UBA6	psi-mi:“MI:0914”(association)	0.350
OSBPL11	DNM1L	psi-mi:“MI:0914”(association)	0.350
PCDHGA9	UBA6	psi-mi:“MI:0914”(association)	0.350
PCGF6	UBA6	psi-mi:“MI:0914”(association)	0.350
RAE1	NHERF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): DNMT3L (Two-hybrid), GDPGP1 (Co-fractionation), PHPT1 (Co-fractionation), PHPT1 (Co-fractionation), PHPT1 (Co-fractionation), PHPT1 (Co-fractionation), PHPT1 (Co-fractionation), PPP2R4 (Co-fractionation), TRAPPC4 (Co-fractionation), PHPT1 (Affinity Capture-MS), PHPT1 (Reconstituted Complex), TPM4 (Affinity Capture-MS), PHPT1 (Co-fractionation), PHPT1 (Affinity Capture-RNA), AASDHPPT (Affinity Capture-MS)

ESM2 similar proteins: A0M8S9, A0M8V0, A0MT11, A1X151, A1Z3X3, A3KFX0, A4GWN3, A7MB16, E1BSI0, P47754, P47897, P59083, P79136, P83468, P97789, Q00PJ7, Q07E00, Q07E23, Q07E36, Q108U5, Q15005, Q28250, Q29221, Q2IBB9, Q2QLA8, Q2QLH5, Q32P66, Q32PA4, Q3T1K5, Q498R7, Q4G061, Q4R512, Q4R5G1, Q5M8Y1, Q5R8L6, Q5RAY6, Q5U3V9, Q5ZKG8, Q5ZKK4, Q66H61

Diamond homologs: P20348, P20349, P54364, P54365, P59083, P83468, P83752, P83753, Q32PA4, Q5R8L6, Q9BM89, Q9BM90, Q9BM91, Q9BM92, Q9BM93, Q9BM94, Q9BM95, Q9BM96, Q9BM97, Q9BM98, Q9BM99, Q9DAK9, Q9NRX4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PHPT1	“down-regulates activity”	KCNN4	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

529 predictions. Top by Δscore:

Variant	Effect	Δscore
9:136849577:GGC:G	donor_gain	1.0000
9:136849578:GC:G	donor_gain	1.0000
9:136849579:C:G	donor_gain	1.0000
9:136849574:G:GG	donor_gain	0.9900
9:136849576:GGGC:G	donor_gain	0.9900
9:136850011:A:AG	acceptor_gain	0.9900
9:136850011:AGC:A	acceptor_gain	0.9900
9:136850012:G:GG	acceptor_gain	0.9900
9:136850012:GC:G	acceptor_gain	0.9900
9:136850012:GCG:G	acceptor_gain	0.9900
9:136849579:C:CG	donor_gain	0.9800
9:136849586:CCATG:C	donor_gain	0.9800
9:136850013:C:CA	acceptor_gain	0.9800
9:136850014:G:A	acceptor_gain	0.9800
9:136849582:A:AG	donor_gain	0.9700
9:136849583:G:GG	donor_gain	0.9700
9:136849591:GTG:G	donor_loss	0.9700
9:136849593:GAGG:G	donor_loss	0.9700
9:136850011:AGCG:A	acceptor_gain	0.9700
9:136850012:GCGG:G	acceptor_gain	0.9700
9:136850751:CCA:C	acceptor_loss	0.9700
9:136850752:CA:C	acceptor_loss	0.9700
9:136850753:A:AG	acceptor_gain	0.9700
9:136850754:G:GA	acceptor_loss	0.9700
9:136850754:G:GG	acceptor_gain	0.9700
9:136850754:GGCCT:G	acceptor_gain	0.9700
9:136850754:GGC:G	acceptor_gain	0.9600
9:136849493:G:GG	donor_gain	0.9500
9:136849554:G:GT	donor_gain	0.9500
9:136850133:CCATG:C	donor_loss	0.9500

AlphaMissense

819 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:136850085:G:C	R78P	0.995
9:136849488:T:C	F20L	0.993
9:136849490:C:A	F20L	0.993
9:136849490:C:G	F20L	0.993
9:136849494:T:C	Y22H	0.993
9:136850088:T:C	I79T	0.992
9:136849567:G:A	G46D	0.991
9:136850093:C:G	H81D	0.991
9:136849493:G:C	K21N	0.990
9:136849493:G:T	K21N	0.990
9:136849566:G:C	G46R	0.990
9:136849587:C:A	H53N	0.990
9:136850084:C:A	R78S	0.990
9:136850127:G:A	G92D	0.990
9:136849587:C:G	H53D	0.989
9:136849589:T:A	H53Q	0.989
9:136849589:T:G	H53Q	0.989
9:136850076:G:A	G75D	0.988
9:136850082:G:A	G77E	0.987
9:136849563:C:A	R45S	0.986
9:136850076:G:T	G75V	0.986
9:136850088:T:A	I79N	0.986
9:136850121:T:A	V90E	0.986
9:136850127:G:T	G92V	0.986
9:136850115:T:C	I88T	0.985
9:136850088:T:G	I79S	0.984
9:136849491:A:G	K21E	0.983
9:136849564:G:C	R45P	0.983
9:136850132:T:C	S94P	0.983
9:136850133:C:T	S94F	0.983

dbSNP variants (sampled 300 via entrez): RS1001213561 (9:136849208 G>A,C), RS1001266011 (9:136848930 G>A,C), RS1002220950 (9:136849845 G>C), RS1002271614 (9:136849728 G>C,T), RS1002376232 (9:136849211 T>C), RS1002789223 (9:136848292 G>A,C), RS1002887387 (9:136848107 C>G,T), RS1002939500 (9:136847922 G>A,C), RS1003946878 (9:136847717 C>T), RS1004625909 (9:136849328 A>C,G), RS1005079803 (9:136849221 C>G,T), RS1006170610 (9:136849720 C>G,T), RS1006467302 (9:136849948 G>A,T), RS1006702176 (9:136848336 C>G,T), RS1007026670 (9:136850438 C>A,T)

Disease associations

OMIM: gene MIM:610167 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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: yes

ChEMBL targets (1): CHEMBL5169200 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 22,046 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1330792	ACETARSONE	4	2,042
CHEMBL456	ETHACRYNIC ACID	4	20,004

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 8 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.24	Kd	57.79	nM	CHEMBL5653589
7.24	ED50	57.79	nM	CHEMBL5653589
5.10	IC50	7900	nM	NORSTICTIC ACID

PubChem BioAssay actives

2 with measured affinity, of 32 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149000: Binding affinity to human PHPT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0578	uM
5,13,17-trihydroxy-7,12-dimethyl-9,15-dioxo-2,10,16-trioxatetracyclo[9.7.0.03,8.014,18]octadeca-1(11),3(8),4,6,12,14(18)-hexaene-4-carbaldehyde	1870205: Inhibition of PHPT1 (unknown origin) using DiFMUP as fluorogenic substrate incubated for 30 mins followed by substrate addition and measured every 60 seconds for 30 mins by fluorogenic assay	ic50	7.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	5
Valproic Acid	affects expression, decreases expression, increases methylation	3
bisphenol A	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression	1
methylparaben	decreases expression	1
sulforaphane	decreases expression	1
tetrabromobisphenol A	decreases expression	1
microcystin RR	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Decitabine	affects expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Diazinon	increases methylation	1
Doxorubicin	increases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5107654	Binding	Inhibition of human PHPT1 expressed in Escherichia coli BL21 (DE3) using pNPP as substrate incubated for 1 hr by multimode microplate reader analysis	Identification of a Target Site for Covalent Inhibition of Protein Phosphohistidine Phosphatase 1. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2GQ	HAP1 PHPT1 (-) 1	Cancer cell line	Male
CVCL_E2GR	HAP1 PHPT1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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