PTPMT1

Summary

PTPMT1 (protein tyrosine phosphatase mitochondrial 1, HGNC:26965) is a protein-coding gene on chromosome 11p11.2, encoding Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (Q8WUK0). Lipid phosphatase which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG). It is a selective cancer dependency (DepMap: 61.8% of cell lines).

Predicted to enable phosphatidylglycerophosphatase activity and phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. Involved in regulation of intrinsic apoptotic signaling pathway. Located in nucleus. Is active in mitochondrion.

Source: NCBI Gene 114971 — RefSeq curated summary.

At a glance

• GWAS associations: 28
• Clinical variants (ClinVar): 37 total — 1 pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 61.8% of screened cell lines
• MANE Select transcript: NM_175732

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26965
Approved symbol	PTPMT1
Name	protein tyrosine phosphatase mitochondrial 1
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Aliases	PLIP, DUSP23, MOSP
Ensembl gene	ENSG00000110536
Ensembl biotype	protein_coding
OMIM	609538
Entrez	114971

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000326656, ENST00000326674, ENST00000426530, ENST00000527079, ENST00000534775, ENST00000905560, ENST00000905561, ENST00000914915, ENST00000914916, ENST00000962873

RefSeq mRNA: 2 — MANE Select: NM_175732 NM_001143984, NM_175732

CCDS: CCDS41643, CCDS44593

Canonical transcript exons

ENST00000326674 — 4 exons

Exon	Start	End
ENSE00002180441	47571471	47573461
ENSE00002180447	47565599	47565796
ENSE00003653456	47569700	47569891
ENSE00003674864	47565906	47565986

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.9916 / max 367.0711, expressed in 1822 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114224	33.4257	1819
114223	3.9238	1577
114220	0.6391	348
114221	0.4202	216
114222	0.3198	155
206278	0.2629	113

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	93.46	gold quality
right testis	UBERON:0004534	93.46	gold quality
testis	UBERON:0000473	92.67	gold quality
putamen	UBERON:0001874	91.96	gold quality
left adrenal gland cortex	UBERON:0035825	91.75	gold quality
left adrenal gland	UBERON:0001234	91.73	gold quality
substantia nigra	UBERON:0002038	91.68	gold quality
hypothalamus	UBERON:0001898	91.62	gold quality
right adrenal gland	UBERON:0001233	91.58	gold quality
caudate nucleus	UBERON:0001873	91.58	gold quality
right adrenal gland cortex	UBERON:0035827	91.53	gold quality
nucleus accumbens	UBERON:0001882	91.42	gold quality
amygdala	UBERON:0001876	91.40	gold quality
temporal lobe	UBERON:0001871	91.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.33	gold quality
adrenal gland	UBERON:0002369	90.69	gold quality
prefrontal cortex	UBERON:0000451	90.64	gold quality
primary visual cortex	UBERON:0002436	90.55	gold quality
adenohypophysis	UBERON:0002196	90.29	gold quality
anterior cingulate cortex	UBERON:0009835	90.17	gold quality
frontal cortex	UBERON:0001870	90.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.07	gold quality
cerebral cortex	UBERON:0000956	89.94	gold quality
Ammon’s horn	UBERON:0001954	89.88	gold quality
brain	UBERON:0000955	89.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.82	gold quality
pituitary gland	UBERON:0000007	89.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.80	gold quality
body of pancreas	UBERON:0001150	89.47	gold quality
right frontal lobe	UBERON:0002810	89.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting PTPMT1, 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-371B-5P	99.99	75.34	4759
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-133A-3P	99.27	71.53	1270

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 61.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• Our data suggest that inhibition of PTPMT1 causes a metabolic crisis in cancer cells that induces cell death, and may be a mechanism by which cancer cells can be sensitized to currently available therapies. (PMID:23326511)
• our data support a model in which MK-STYX controls apoptosis by negatively regulating PTPMT1. (PMID:24709986)
• A key role for HIF-2alpha-induced Ptpmt1 up-regulation in proliferation, survival and glucose metabolism of erythroleukemia cells. (PMID:26898802)
• SRSF1 regulates lung cancer cell radioresistance through modulating PTPMT1 splicing. Reduced SRSF1 favors the production of short isoforms of PTPMT1 upon ionizing radiation, which in turn promotes phosphorylation of AMPK, thereby inducing DNA double-strand break to sensitize cancer cells to irradiation. (PMID:30429088)
• Genome-wide CRISPR-Cas9 knockout library screening identified PTPMT1 in cardiolipin synthesis is crucial to survival in hypoxia in liver cancer. (PMID:33503428)
• Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1. (PMID:33992102)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptpmt1	ENSDARG00000013860
mus_musculus	Ptpmt1	ENSMUSG00000063235
rattus_norvegicus	Ptpmt1	ENSRNOG00000009723
drosophila_melanogaster	PTPMT1	FBGN0039111
caenorhabditis_elegans		WBGENE00009207

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), DUSP3 (ENSG00000108861), DUSP16 (ENSG00000111266), 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

Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 — Q8WUK0 (reviewed: Q8WUK0)

Alternative names: PTEN-like phosphatase, Phosphoinositide lipid phosphatase, Protein-tyrosine phosphatase mitochondrial 1

All UniProt accessions (2): Q8WUK0, E9PQM0

UniProt curated annotations — full annotation on UniProt →

Function. Lipid phosphatase which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG). PGP is an essential intermediate in the biosynthetic pathway of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle. Has also been shown to display phosphatase activity toward phosphoprotein substrates, specifically mediates dephosphorylation of mitochondrial proteins, thereby playing an essential role in ATP production. Has probably a preference for proteins phosphorylated on Ser and/or Thr residues compared to proteins phosphorylated on Tyr residues. Probably involved in regulation of insulin secretion in pancreatic beta cells. Prevents intrinsic apoptosis, by regulating mitochondrial membrane integrity.

Subunit / interactions. Interacts with STYXL1; the interaction inhibits PTPMT1 catalytic activity.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Neurodevelopmental disorder with ataxia and brain abnormalities (NEDAXBA) [MIM:621199] An autosomal recessive neurodevelopmental disorder with neonatal or infantile onset, and characterized by developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy and bulbar dysfunction. Brain imaging reveals a variable combination of corpus callosum thinning, cerebellar atrophy and white matter changes. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Phospholipid metabolism; phosphatidylglycerol biosynthesis; phosphatidylglycerol from CDP-diacylglycerol: step 2/2.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WUK0-1	1	yes
Q8WUK0-2	2
Q8WUK0-3	3

RefSeq proteins (2): NP_001137456, NP_783859* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR042165	PTPMT1	Family
IPR044596	PTPMT1-like	Family

Pfam: PF00782

Catalyzed reactions (Rhea), 8 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)
• a 1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycero-3’-phosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycerol) + phosphate (RHEA:33751)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1’-sn-glycerol-3’-phosphate) + H2O = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1’-sn-glycerol) + phosphate (RHEA:42304)
• 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol) + phosphate (RHEA:42308)
• a 1-acyl-2-hexanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + H2O = a 1-acyl-2-hexanoyl-sn-glycero-3-phospho-(1D-myo-inositol) + phosphate (RHEA:42320)
• 1,2-dibutyryl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + H2O = 1,2-dibutyryl-sn-glycero-3-phospho-(1D-myo-inositol) + phosphate (RHEA:42584)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (9 total): splice variant 3, transit peptide 1, chain 1, domain 1, active site 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUK0-F1	91.76	0.71

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): 132 (phosphocysteine intermediate)

Mutagenesis-validated functional residues (1):

Position	Phenotype
132	probable loss of catalytic activity. does not affect interaction with styxl1.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483148	Synthesis of PG

MSigDB gene sets: 193 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_APOPTOTIC_SIGNALING_PATHWAY, WANG_LMO4_TARGETS_DN, GOBP_CILIUM_ORGANIZATION, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_ORGANELLE_ASSEMBLY

GO Biological Process (8): cardiolipin biosynthetic process (GO:0032049), mitochondrial fragmentation involved in apoptotic process (GO:0043653), regulation of intrinsic apoptotic signaling pathway (GO:2001242), protein dephosphorylation (GO:0006470), lipid metabolic process (GO:0006629), phosphatidylglycerol biosynthetic process (GO:0006655), phospholipid biosynthetic process (GO:0008654), dephosphorylation (GO:0016311)

GO Molecular Function (8): phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity (GO:0004439), protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), phosphatidylglycerophosphatase activity (GO:0008962), phosphatidylinositol-5-phosphate phosphatase activity (GO:0102091), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatidylinositol phosphate 5-phosphatase activity	2
phosphoprotein phosphatase activity	2
phosphatase activity	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
phosphatidylglycerol biosynthetic process	1
cardiolipin metabolic process	1
apoptotic mitochondrial changes	1
intrinsic apoptotic signaling pathway	1
regulation of intracellular signal transduction	1
regulation of apoptotic signaling pathway	1
dephosphorylation	1
protein modification process	1
primary metabolic process	1
phosphatidylglycerol metabolic process	1
glycerophospholipid biosynthetic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
phosphate-containing compound metabolic process	1
phosphatidylinositol-4,5-bisphosphate phosphatase activity	1
phosphatidylinositol monophosphate phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPMT1	TAMM41	Q96BW9	772
PTPMT1	PTEN	P60484	715
PTPMT1	PGS1	Q32NB8	657
PTPMT1	CRLS1	Q9UJA2	632
PTPMT1	TAFAZZIN	Q16635	621
PTPMT1	EPM2A	O95278	491
PTPMT1	PRELID1	Q9Y255	488
PTPMT1	KBTBD4	Q9NVX7	461
PTPMT1	ACP1	P24666	448
PTPMT1	DUSP3	P51452	446
PTPMT1	MTCH2	Q9Y6C9	436
PTPMT1	DOLPP1	Q86YN1	420
PTPMT1	FGR	P09769	419
PTPMT1	PTS	Q03393	409
PTPMT1	BLOC1S4	Q9NUP1	409

IntAct

172 interactions, top by confidence:

A	B	Type	Score
PTPMT1	MDFI	psi-mi:“MI:0915”(physical association)	0.780
MDFI	PTPMT1	psi-mi:“MI:0915”(physical association)	0.780
RGS20	PTPMT1	psi-mi:“MI:0915”(physical association)	0.720
PTPMT1	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	PTPMT1	psi-mi:“MI:0915”(physical association)	0.720
PTPMT1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
PTPMT1	KRT31	psi-mi:“MI:0915”(physical association)	0.720
KRTAP9-2	PTPMT1	psi-mi:“MI:0915”(physical association)	0.720
PTPMT1	RGS20	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	PTPMT1	psi-mi:“MI:0915”(physical association)	0.720
KRT31	PTPMT1	psi-mi:“MI:0915”(physical association)	0.720
PTPMT1	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.720
PTPMT1	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	PTPMT1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (231): PTPMT1 (Two-hybrid), PTPMT1 (Two-hybrid), PTPMT1 (Two-hybrid), PTPMT1 (Two-hybrid), PTPMT1 (Two-hybrid), PTPMT1 (Two-hybrid), PTPMT1 (Two-hybrid), PTPMT1 (Two-hybrid), PTPMT1 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), PTPMT1 (Affinity Capture-MS)

ESM2 similar proteins: A4D256, A4IHU7, O14830, O35239, O35385, O95147, P0C591, P0C592, P0C593, P0C594, P0C595, P0C596, P0C597, P0C598, P0C599, P0C5A0, P0C5A1, P0C5A2, P43378, P51452, Q16828, Q17QM8, Q29RA3, Q2KJ36, Q4KL92, Q4RQD3, Q566R7, Q5RD73, Q5XHB2, Q641Z2, Q64346, Q68J44, Q6AXW7, Q6GQJ8, Q86BN8, Q8BK84, Q8K4T5, Q8WTR2, Q8WUK0, Q90W58

Diamond homologs: B4F7B7, O13632, O55737, P0C089, P0C593, P0C596, P0C597, P0C599, P28562, P28563, Q05922, Q39491, Q4RQD3, Q64623, Q66GT5, Q6NKR2, Q6NN85, Q84JU4, Q86BN8, Q8R4V2, Q8WUK0, Q90W58, Q91790, Q9BY84, Q9JIM4, Q9M8K7, Q9ZQP1, P0C595, Q13115, Q17QJ3, Q55CS7, Q5FVI9, Q5R6H6, Q8BK84, Q9BV47, Q9D700, Q9H1R2, A2A3K4, A4D256, A6N3Q4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PTPMT1	up-regulates	phosphatidylglycerol(1-)	“chemical modification”
PTPMT1	“down-regulates quantity”	“1-(3-sn-phosphatidyl)-sn-glycerol 3-phosphate(3-)”	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 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
Keratinization	15	11.3×	9e-10

GO biological processes:

GO term	Partners	Fold	FDR
epidermis development	6	14.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	27
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3899900	NM_175732.3(PTPMT1):c.255G>C (p.Gln85His)	Pathogenic

SpliceAI

356 predictions. Top by Δscore:

Variant	Effect	Δscore
11:47565794:CAGG:C	donor_loss	1.0000
11:47565795:AGG:A	donor_loss	1.0000
11:47565798:T:A	donor_loss	1.0000
11:47565904:A:AG	acceptor_gain	1.0000
11:47565904:AGCT:A	acceptor_gain	1.0000
11:47565905:G:GG	acceptor_gain	1.0000
11:47565905:GCT:G	acceptor_gain	1.0000
11:47565905:GCTG:G	acceptor_gain	1.0000
11:47565987:G:GA	donor_loss	1.0000
11:47569678:A:AG	acceptor_gain	1.0000
11:47569678:ATACT:A	acceptor_gain	1.0000
11:47569680:A:AG	acceptor_gain	1.0000
11:47569680:ACT:A	acceptor_gain	1.0000
11:47569682:T:TA	acceptor_gain	1.0000
11:47569784:G:GT	donor_gain	1.0000
11:47571447:T:A	acceptor_gain	1.0000
11:47565792:GCCAG:G	donor_gain	0.9900
11:47565797:G:GG	donor_gain	0.9900
11:47565904:AGCTG:A	acceptor_gain	0.9900
11:47565905:GC:G	acceptor_gain	0.9900
11:47565905:GCTGG:G	acceptor_gain	0.9900
11:47569679:T:G	acceptor_gain	0.9900
11:47569680:ACTG:A	acceptor_gain	0.9900
11:47569682:T:A	acceptor_loss	0.9900
11:47569683:G:A	acceptor_gain	0.9900
11:47569685:T:TA	acceptor_gain	0.9900
11:47569686:G:A	acceptor_gain	0.9900
11:47569691:T:TA	acceptor_gain	0.9900
11:47569692:G:A	acceptor_gain	0.9900
11:47569695:TCCAG:T	acceptor_loss	0.9900

AlphaMissense

1283 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:47569857:G:T	R138M	0.995
11:47569859:A:C	S139R	0.995
11:47569861:T:A	S139R	0.995
11:47569861:T:G	S139R	0.995
11:47569793:T:C	F117L	0.991
11:47569795:T:A	F117L	0.991
11:47569795:T:G	F117L	0.991
11:47569843:G:C	K133N	0.991
11:47569843:G:T	K133N	0.991
11:47569703:T:A	W87R	0.989
11:47569703:T:C	W87R	0.989
11:47569857:G:C	R138T	0.989
11:47569878:C:A	A145E	0.989
11:47569884:T:C	L147P	0.989
11:47571495:G:C	A158P	0.989
11:47569827:T:A	V128D	0.988
11:47565959:G:C	E76D	0.987
11:47565959:G:T	E76D	0.987
11:47569840:T:G	C132W	0.987
11:47569858:G:C	R138S	0.987
11:47569858:G:T	R138S	0.987
11:47571559:T:A	L179H	0.987
11:47565937:T:A	I69N	0.985
11:47569784:G:A	G114R	0.985
11:47569784:G:C	G114R	0.985
11:47569880:T:G	Y146D	0.985
11:47569705:G:C	W87C	0.984
11:47569705:G:T	W87C	0.984
11:47569833:T:A	V130E	0.984
11:47569835:C:G	H131D	0.984

dbSNP variants (sampled 300 via entrez): RS1000200693 (11:47565230 G>A), RS1000305009 (11:47571536 C>T), RS1001220785 (11:47565469 C>A,G,T), RS1001864637 (11:47564791 AAAAC>A,AAAACAAAC), RS1001981342 (11:47573244 A>C,G), RS1002290501 (11:47571968 T>G), RS1002486627 (11:47566550 G>A,T), RS1002655392 (11:47570036 C>A), RS1002783327 (11:47570528 C>T), RS1003152013 (11:47569541 G>A,T), RS1003539012 (11:47567958 G>A), RS1004261992 (11:47570356 G>T), RS1004646669 (11:47570100 A>C), RS1004720527 (11:47564712 A>C), RS1004734071 (11:47572059 G>A)

Disease associations

OMIM: gene MIM:609538 | disease phenotypes: MIM:621199

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder with ataxia and brain abnormalities (MONDO:0978300)

Orphanet (0):

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000448	Prominent nose
HP:0000543	Optic disc pallor
HP:0000577	Exotropia
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0000768	Pectus carinatum
HP:0000817	Reduced eye contact
HP:0000822	Hypertension
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0002061	Lower limb spasticity
HP:0002120	Cerebral cortical atrophy

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST005232_56	Neuroticism	1.000000e-16
GCST005984_53	Glomerular filtration rate	3.000000e-10
GCST006229_3	Hypertension	7.000000e-08
GCST006231_48	Mean arterial pressure	4.000000e-06
GCST006923_11	Loneliness	1.000000e-07
GCST006924_13	Loneliness (MTAG)	1.000000e-08
GCST007293_118	Body fat distribution (arm fat ratio)	3.000000e-08
GCST007293_19	Body fat distribution (arm fat ratio)	2.000000e-10
GCST007293_45	Body fat distribution (arm fat ratio)	5.000000e-14
GCST007294_28	Body fat distribution (trunk fat ratio)	6.000000e-09
GCST007294_9	Body fat distribution (trunk fat ratio)	4.000000e-06
GCST007295_159	Body fat distribution (leg fat ratio)	1.000000e-18
GCST007295_24	Body fat distribution (leg fat ratio)	7.000000e-08
GCST007295_50	Body fat distribution (leg fat ratio)	2.000000e-12
GCST007344_1	Estimated glomerular filtration rate	9.000000e-13
GCST007825_4	Alzheimer’s disease or fasting glucose levels (pleiotropy)	3.000000e-16
GCST008103_60	Bipolar disorder	5.000000e-07
GCST008357_37	Mood instability	9.000000e-14
GCST009240_215	Serum metabolite levels (CMS)	4.000000e-10
GCST009240_298	Serum metabolite levels (CMS)	2.000000e-13
GCST009240_332	Serum metabolite levels (CMS)	9.000000e-10
GCST009240_419	Serum metabolite levels (CMS)	1.000000e-07
GCST009242_118	Serum metabolite levels	2.000000e-07
GCST009242_264	Serum metabolite levels	7.000000e-13
GCST009242_387	Serum metabolite levels	9.000000e-10
GCST009242_426	Serum metabolite levels	4.000000e-09
GCST010136_2	Fruit consumption	5.000000e-09
GCST010703_36	Brain morphology (MOSTest)	8.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0006340	mean arterial pressure
EFO:0007865	loneliness measurement
EFO:0004341	body fat distribution
EFO:0008475	mood instability measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2052033 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.79	IC50	1620	nM	CHEMBL2000194

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
alpha phellandrene	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	affects response to substance	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Quercetin	decreases expression	1
Thiram	decreases expression	1
Tunicamycin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2061291	Binding	Inhibition of PTPMT1 using 3-O-Methylfluorescein phosphate as substrate incubated for 10 mins prior to substrate addition by fluorometry	Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases. — Bioorg Med Chem

Clinical trials (associated diseases)

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