PTPMT1
protein-codingprotein tyrosine phosphatase mitochondrial 1, the group of Phosphoinositide phosphatases|Atypical dual specificity phosphatases
Gene summary
Predicted to enable phosphatidylglycerophosphatase activity and phosphatidylinositol-5-phosphate phosphatase activity. Involved in cardiolipin biosynthetic process; mitochondrial fragmentation involved in apoptotic process; and regulation of intrinsic apoptotic signaling pathway. Located in nucleus. Is active in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PTPMT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_175732.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 5 | ||||
| missense | 1 | 27 | 2 | 30 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 27 | 7 | 0 | 35 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_783859.1 | 4 | MANE Select | |
| Ensembl | ENSP00000325958.9 | 4 | MANE Select | |
| RefSeq | NP_001137456.1 | 2 | Standard | |
| Ensembl | ENSP00000325882.8 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ptpmt1 | Danio rerio | Structure: skeletal muscle Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inositol Metabolism
- Phospholipid Biosynthesis
- Metabolism of lipids
- cardiolipin biosynthesis
- Metabolism
Biological Process
- cardiolipin biosynthetic process
- peptidyl-tyrosine dephosphorylation
- regulation of intrinsic apoptotic signaling pathway
Molecular Function
- phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity
- protein tyrosine phosphatase activity
- protein binding
- protein tyrosine/serine/threonine phosphatase activity
- phosphatidylglycerophosphatase activity
Cellular Component
- nucleus
- mitochondrial inner membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326674
- Coding exons
- 4
- Length
- 8032
- Individuals with no LoFs
- 124775
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 124789
- p
- 0.0000561
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.489 | 94 | 108 | 0.868 | 0.00000573 | 1264 |
| Missense (PolyPhen) | 43 | 50.455 | 0.85225 | 551 | ||
| Synonymous | -0.400 | 50 | 46.5 | 1.07 | 0.00000233 | 427 |
| Loss of Function | 1.28 | 4 | 7.89 | 0.507 | 3.38e-7 | 91 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Lipid phosphatase which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG) (By similarity). PGP is an essential intermediate in the biosynthetic pathway of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle (By similarity). 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 (By similarity). Has probably a preference for proteins phosphorylated on Ser and/or Thr residues compared to proteins phosphorylated on Tyr residues (By similarity). Probably involved in regulation of insulin secretion in pancreatic beta cells (By similarity). May prevent intrinsic apoptosis, probably by regulating mitochondrial membrane integrity (PubMed:24709986). {ECO:0000250|UniProtKB:P0C089, ECO:0000250|UniProtKB:Q66GT5, ECO:0000269|PubMed:24709986}.;
Recessive Scores
- pRec
- 0.124
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.653
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |