MTMR6

Chr 13

myotubularin related protein 6

NCBI Gene: 9107ENSG00000139505UniProt: Q9Y217OMIM: 603561

The protein is a lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, regulating cellular processes including protein transport, macropinocytosis, and T-cell function. Mutations in this gene cause Charcot-Marie-Tooth disease type 4B1, an autosomal recessive peripheral neuropathy characterized by demyelinating features and focally folded myelin sheaths. The gene shows high tolerance to loss-of-function variants (LOEUF 0.756), which is consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.76
Clinical Summary— MTMR6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 78 VUS of 129 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.000
Z-score 2.70
OE 0.51 (0.35–0.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.87Z-score
OE missense 0.86 (0.78–0.95)
276 obs / 319.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.35–0.76)
0≤0.351.4
Missense OE0.86 (0.78–0.95)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 18 / 35.3Missense obs/exp: 276 / 319.9Syn Z: 0.91
DN
0.6259th %ile
GOF
0.5857th %ile
LOF
0.2971th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic2
VUS78
Likely Benign6
31
Pathogenic
2
Likely Pathogenic
78
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
2
0
2
VUS
0
75
3
0
78
Likely Benign
0
6
0
0
6
Benign
0
0
0
0
0
Total081360117

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

View in ClinVar →

Protein Context — Lollipop Plot

MTMR6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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