MTMR3

Chr 22

myotubularin related protein 3

Also known as: FYVE-DSP1, ZFYVE10

NCBI Gene: 8897ENSG00000100330UniProt: Q13615

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]

197
ClinVar variants
22
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MTMR3
⚡
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
22 Pathogenic / Likely Pathogenic· 144 VUS of 197 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.26LOEUF
pLI 0.999
Z-score 6.17
OE 0.15 (0.09–0.26)
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.
1.99Z-score
OE missense 0.78 (0.73–0.84)
524 obs / 669.2 exp
Tolerant

Mild missense constraint

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.0.15 (0.09–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.73–0.84)
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.1.00
0≤1.21.6
LoF obs/exp: 9 / 60.9Missense obs/exp: 524 / 669.2Syn Z: 0.02

ClinVar Variant Classifications

197 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS144
Likely Benign5
Benign1
21
Pathogenic
1
Likely Pathogenic
144
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
142
2
0
144
Likely Benign
0
3
0
2
5
Benign
0
0
1
0
1
Total0145252172

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

View in ClinVar →

Protein Context — Lollipop Plot

MTMR3 · 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
New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD.
Larabi A et al.·Autophagy
2020Review
MTMR3 risk alleles enhance Toll Like Receptor 9-induced IgA immunity in IgA nephropathy.
Wang YN et al.·Kidney Int
2023
MiR-99a exerts anti-metastasis through inhibiting myotubularin-related protein 3 expression in oral cancer.
Kuo YZ et al.·Oral Dis
2014
Genetics of childhood-onset inflammatory bowel disease.
Henderson P et al.·Inflamm Bowel Dis
2011Review
Exosomal miR-1910-3p promotes proliferation, metastasis, and autophagy of breast cancer cells by targeting MTMR3 and activating the NF-κB signaling pathway.
Wang B et al.·Cancer Lett
2020
Comprehensive Analysis of Diabetes Mellitus-related Gene Expression and Associated Prognoses in Human Lung Cancer.
Yang J et al.·Curr Cancer Drug Targets
2023
Genetic polymorphism at miR-181a binding site contributes to gastric cancer susceptibility.
Lin Y et al.·Carcinogenesis
2012
Genetic susceptibility and potential therapeutic targets of unruptured intracranial aneurysms: A genome-wide study based on Mendelian randomization.
Liu S et al.·Clin Neurol Neurosurg
2025
miR-93 regulates liver tumor initiating cells expansion and predicts chemotherapeutic response of patients.
Li J et al.·Arch Biochem Biophys
2021Cohort
Genetic association and functional role of Crohn disease risk alleles involved in microbial sensing, autophagy, and endoplasmic reticulum (ER) stress.
Hoefkens E et al.·Autophagy
2013Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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