HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
8 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MTMR12
myotubularin related protein 12
Chromosome 5 · 5p13.3
NCBI Gene: 54545Ensembl: ENSG00000150712.12HGNC: HGNC:18191UniProt: Q9C0I1
36PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoplasmprotein bindingmembranephosphatidylinositol biosynthetic processneurodegenerative diseasemultiple sclerosisAlzheimer diseaseParkinson disease
✦AI Summary

MTMR12 (myotubularin related protein 12) is a catalytically inactive lipid phosphatase that functions as a critical adapter protein for the myotubularin (MTM1) phosphatase complex. MTMR12 lacks the conserved HCX(5)R catalytic motif characteristic of active phosphatases 1 but forms functional heteroligomers with MTM1 through direct protein-protein interactions 2. This interaction stabilizes MTM1 protein levels and regulates its intracellular localization from the plasma membrane to the cytosol 3, which is essential for skeletal muscle maintenance and normal myotubule organization 2. Loss of MTMR12 results in reduced MTM1 stability and pathological muscle changes including central nucleation, myofiber hypotrophy, and disorganized triads similar to X-linked myotubular myopathy 2. Clinically, MTMR12 variants have been identified as genetic modifiers influencing disease susceptibility in α1-antitrypsin deficiency through autophagy regulation 4 and in a genome-wide association study as a locus associated with estimated glomerular filtration slope decline and chr5 kidney disease risk in East Asian populations 5. These findings suggest MTMR12 participates in proteostasis pathways beyond skeletal muscle, with potential therapeutic implications for stabilizing the MTM1-MTMR12 complex in myopathies.

Sources cited
1
MTMR12 (3-PAP) is a catalytically inactive adapter subunit lacking the HCX(5)R catalytic motif
PMID: 11504939
2
MTMR12 (3-PAP) functions as an adapter regulating myotubularin intracellular location and stability
PMID: 12847286
3
Loss of MTMR12 impairs MTM1 stability and causes centronuclear myopathy phenotype in muscle
PMID: 23818870
4
MTMR12 variants are putative modifiers of hepatic phenotype in α1-antitrypsin deficiency through autophagy
PMID: 38557779
5
MTMR12 locus is associated with eGFR slope and chronic kidney disease risk in Taiwanese population
PMID: 40906351
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.48Moderate
Alzheimer diseaseOpen Targets
0.43Moderate
lysosomal storage diseaseOpen Targets
0.43Moderate
multiple sclerosisOpen Targets
0.43Moderate
Parkinson diseaseOpen Targets
0.43Moderate
adrenal gland hyperfunctionOpen Targets
0.12Weak
poisoningOpen Targets
0.11Weak
chondromalaciaOpen Targets
0.10Weak
response to xenobiotic stimulusOpen Targets
0.10Weak
Sensorineural hearing impairmentOpen Targets
0.07Suggestive
hearing lossOpen Targets
0.06Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.05Suggestive
X-linked retinal dysplasiaOpen Targets
0.05Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.05Suggestive
Stargardt diseaseOpen Targets
0.05Suggestive
X-linked retinoschisisOpen Targets
0.04Suggestive
coloboma of optic nerveOpen Targets
0.03Suggestive
liver diseaseOpen Targets
0.02Suggestive
X-linked myotubular myopathyOpen Targets
0.02Suggestive
juvenile dermatomyositisOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MTMR2Protein interaction98%MTM1Protein interaction95%VAC14Shared pathway50%PITPNM3Shared pathway50%CDIPTShared pathway50%SACM1LShared pathway50%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
99%
Liver
98%
Heart
95%
Lung
72%
Brain
72%
Gene Interaction Network
Click a node to explore
MTMR12MTMR2MTM1VAC14PITPNM3CDIPTSACM1L
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9C0I1
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.39Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.28 [0.20–0.39]
RankingsWhere MTMR12 stands among ~20K protein-coding genes
  • #10,818of 20,598
    Most Researched36
  • #1,944of 17,882
    Most Constrained (LOEUF)0.39 · top quartile
Genes detectedMTMR12
Sources retrieved8 papers
Response time—
📄 Sources
8▼
1
Variants in autophagy genes MTMR12 and FAM134A are putative modifiers of the hepatic phenotype in α1-antitrypsin deficiency.
PMID: 38557779
Hepatology · 2024
1.00
2
Genome-wide polygenic risk score for estimated glomerular filtration slope predicts chronic kidney disease in a Taiwanese population.
PMID: 40906351
J Nephrol · 2025
0.88
3
Transmitted deletions of medial 5p and learning difficulties; does the cadherin cluster only become penetrant when flanking genes are deleted?
PMID: 21965044
Am J Med Genet A · 2011
0.75
4
PI3K and RAC signalling in leukocyte and cancer cell migration.
PMID: 16777617
Bull Cancer · 2006
0.63
5
Loss of catalytically inactive lipid phosphatase myotubularin-related protein 12 impairs myotubularin stability and promotes centronuclear myopathy in zebrafish.
PMID: 23818870
PLoS Genet · 2013
0.50