MTMR4

Chr 17

myotubularin related protein 4

Also known as: FYVE-DSP2, ZFYVE11

NCBI Gene: 9110ENSG00000108389UniProt: Q9NYA4

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]

0
Active trials
147
ClinVar variants
14
Pathogenic / LP
3.5
Missense Z· constrained
0.25
LOEUF· LoF intolerant
6
Pubs (2 yr)
Clinical Summary— MTMR4
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 125 VUS of 147 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.25LOEUF
pLI 1.000
Z-score 6.06
OE 0.14 (0.08–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.49Z-score
OE missense 0.62 (0.57–0.68)
424 obs / 680.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.14 (0.08–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.62 (0.57–0.68)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 8 / 57.7Missense obs/exp: 424 / 680.4Syn Z: 0.73

ClinVar Variant Classifications

147 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic2
VUS125
Likely Benign5
Benign3
12
Pathogenic
2
Likely Pathogenic
125
VUS
5
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
2
0
2
VUS
0
123
2
0
125
Likely Benign
0
5
0
0
5
Benign
0
0
0
3
3
Total0128163147

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MTMR4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
RAF1 kinase contributes to autophagic lysosome reformation.
Toifl S et al.·Cell Rep
2025
Biomarkers for diagnosing pulmonary tuberculosis in adolescents: Peripheral blood monocyte myotubularin-related protein 4 and oncostatin M genes.
Sha Y et al.·Tuberculosis (Edinb)
2025
Deciphering the Molecular Mechanism Underlying African Animal Trypanosomiasis by Means of the 1000 Bull Genomes Project Genomic Dataset
Rajavel A et al.·Biology (Basel)
2022Functional
Joint proteomic and metabolomic analysis reveals renal metabolic remodeling of chronic heart failure mice.
Wang C et al.·J Pharm Biomed Anal
2024Functional
Meta-analysis of RNA-Seq datasets highlights novel genes/pathways involved in fat deposition in fat-tail of sheep
Hosseini SF et al.·Front Vet Sci
2023
Nobiletin Inhibits Breast Cancer Stem Cell by Regulating the Cell Cycle: A Comprehensive Bioinformatics Analysis and In Vitro Experiments.
Hermawan A et al.·Nutr Cancer
2024
Identification of the miRNA-mRNA regulatory network associated with radiosensitivity in esophageal cancer based on integrative analysis of the TCGA and GEO data
Chen H et al.·BMC Med Genomics
2022
Identification of biomarkers based on ubiquitin-correlated genes for predicting immune profile and drug sensitivity in lung adenocarcinoma.
Li Y et al.·Front Pharmacol
2025
Top 8 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients