PTPRM
protein-codingprotein tyrosine phosphatase receptor type M, the group of Fibronectin type III domain containing|I-set domain containing|Protein tyrosine phosphatases receptor type|Ig-like cell adhesion molecule family
Gene summary
The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP has been shown to mediate cell-cell aggregation through the interaction with another molecule of this PTP on an adjacent cell. This PTP can interact with scaffolding protein RACK1/GNB2L1, which may be necessary for the downstream signaling in response to cell-cell adhesion. Alternative splicing results in multiple transcripts encoding distinct isoforms. [provided by RefSeq, Jul 2008]
- PTPRL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~840.1 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 PTPRM variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001105244.2. 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 | 3 | 13 | 10 | 26 | ||
| missense | 167 | 3 | 1 | 171 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 177 | 16 | 11 | 204 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001098714.1 | 33 | MANE Select | |
| Ensembl | ENSP00000463325.1 | 33 | MANE Select | |
| RefSeq | NP_001365071.1 | 27 | Standard | |
| RefSeq | NP_001365072.1 | 29 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Adherens junction - Homo sapiens (human)
- Nectin adhesion pathway
Biological Process
- negative regulation of endothelial cell proliferation
- protein dephosphorylation
- homophilic cell adhesion via plasma membrane adhesion molecules
- signal transduction
- negative regulation of endothelial cell migration
Molecular Function
- protein tyrosine phosphatase activity
- transmembrane receptor protein tyrosine phosphatase activity
- protein binding
- identical protein binding
- cadherin binding
Cellular Component
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- cell-cell junction
- cell-cell adherens junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000580170
- Coding exons
- 33
- Length
- 840080
- Individuals with no LoFs
- 125667
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 81
- Defined
- 125748
- p
- 0.000322
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.84 | 616 | 849 | 0.725 | 0.0000478 | 9613 |
| Missense (PolyPhen) | 169 | 333.59 | 0.50661 | 3788 | ||
| Synonymous | -0.566 | 330 | 317 | 1.04 | 0.0000189 | 2809 |
| Loss of Function | 7.25 | 12 | 83.4 | 0.144 | 0.00000463 | 918 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0.0054 | 0.0054 | notable |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in cell-cell adhesion through homophilic interactions. May play a key role in signal transduction and growth control. {ECO:0000269|PubMed:16456543}.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.421
- RVIS EVS
- -2.03
- RVIS percentile EVS
- 1.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.617
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |