MTMR4
protein-codingmyotubularin related protein 4, the group of Zinc fingers FYVE-type|Myotubularins|Phosphoinositide phosphatases
Gene summary
Enables several functions, including R-SMAD binding activity; phosphatidylinositol phosphate phosphatase activity; and protein phosphatase binding activity. Involved in several processes, including midbody abscission; negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway; and phosphatidylinositol dephosphorylation. Located in early endosome membrane; late endosome membrane; and recycling endosome membrane. Is active in early phagosome membrane and endosome membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.4 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 MTMR4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001378067.1. 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 | 1 | 3 | 4 | |||
| missense | 126 | 5 | 131 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 131 | 5 | 3 | 139 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001364996.1 | 18 | MANE Select | |
| Ensembl | ENSP00000507664.1 | 18 | MANE Select | |
| RefSeq | NP_001364995.1 | 18 | Standard | |
| RefSeq | NP_004678.3 | 18 | 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)
- Signal Transduction
- Metabolism of lipids
Biological Process
- protein dephosphorylation
- phosphatidylinositol biosynthetic process
- transforming growth factor beta receptor signaling pathway
- response to denervation involved in regulation of muscle adaptation
- negative regulation of transforming growth factor beta receptor signaling pathway
Molecular Function
- phosphatidylinositol-3-phosphatase activity
- protein serine/threonine phosphatase activity
- protein tyrosine phosphatase activity
- protein binding
- protein phosphatase binding
Cellular Component
- extracellular space
- endosome
- cytosol
- early endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000323456
- Coding exons
- 18
- Length
- 28369
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.49 | 424 | 680 | 0.623 | 0.0000390 | 7877 |
| Missense (PolyPhen) | 139 | 323.85 | 0.42921 | 3580 | ||
| Synonymous | 0.730 | 246 | 261 | 0.943 | 0.0000145 | 2339 |
| Loss of Function | 6.06 | 8 | 57.7 | 0.139 | 0.00000314 | 632 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000061 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Dephosphorylates proteins phosphorylated on Ser, Thr, and Tyr residues and low molecular weight phosphatase substrate para-nitrophenylphosphate. Phosphorylates phosphatidylinositol 3,4,5-trisphosphate (PIP3). {ECO:0000269|PubMed:11302699}.;
Intolerance Scores
- LoFtool
- 0.0342
- RVIS EVS
- -0.55
- RVIS percentile EVS
- 19.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.926
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |