MTMR3
protein-codingmyotubularin related protein 3, the group of Myotubularins|Phosphoinositide phosphatases|MicroRNA protein coding host genes|Zinc fingers FYVE-type
Gene summary
This gene encodes a member of the myotubularin dual specificity protein phosphatase gene family. The encoded protein is structurally similar to myotubularin but in addition contains a FYVE domain and an N-terminal PH-GRAM domain. The protein can self-associate and also form heteromers with another myotubularin related protein. The protein binds to phosphoinositide lipids through the PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. The encoded protein has been observed to have a perinuclear, possibly membrane-bound, distribution in cells, but it has also been found free in the cytoplasm. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~147.7 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 MTMR3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021090.4. 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 | 2 | 2 | ||||
| missense | 147 | 3 | 150 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 151 | 5 | 0 | 156 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066576.1 | 18 | MANE Select | |
| Ensembl | ENSP00000384651.3 | 18 | MANE Select | |
| RefSeq | NP_694690.1 | 18 | Standard | |
| RefSeq | NP_694691.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inositol phosphate metabolism - Homo sapiens (human)
- Autophagy - animal - Homo sapiens (human)
- Phosphatidylinositol signaling system - Homo sapiens (human)
- Metabolism of lipids
- 3-phosphoinositide degradation
Biological Process
- protein dephosphorylation
- phosphatidylinositol biosynthetic process
- macroautophagy
- peptidyl-tyrosine dephosphorylation
- cellular response to glucose starvation
Molecular Function
- phosphatidylinositol-3-phosphatase activity
- protein serine/threonine phosphatase activity
- protein tyrosine phosphatase activity
- protein binding
- protein phosphatase binding
Cellular Component
- cytoplasm
- cytosol
- membrane
- extrinsic component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000401950
- Coding exons
- 18
- Length
- 147712
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125748
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.00 | 524 | 669 | 0.783 | 0.0000373 | 7858 |
| Missense (PolyPhen) | 198 | 320.55 | 0.6177 | 3761 | ||
| Synonymous | 0.0182 | 253 | 253 | 0.999 | 0.0000144 | 2335 |
| Loss of Function | 6.17 | 9 | 61.0 | 0.148 | 0.00000336 | 656 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000057 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate. May also dephosphorylate proteins phosphorylated on Ser, Thr, and Tyr residues (PubMed:10733931). {ECO:0000269|PubMed:10733931, ECO:0000269|PubMed:11676921}.;
Recessive Scores
- pRec
- 0.120
Intolerance Scores
- LoFtool
- 0.0122
- RVIS EVS
- -0.9
- RVIS percentile EVS
- 10.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- N
- Indispensability score
- 0.102
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |