MTMR6

Chr 13

myotubularin related protein 6

NCBI Gene: 9107 ENSG00000139505 UniProt: Q9Y217

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.

ResearchSummary from RefSeq, UniProt

Enables phosphatidylinositol-3,5-bisphosphate phosphatase activity and phosphatidylinositol-3-phosphate phosphatase activity. Involved in phosphatidylinositol dephosphorylation. Located in cytoplasm and nuclear envelope. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.51 (0.35–0.76)

0≤0.351.4

Missense OE?0.86 (0.78–0.95)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 18 / 35.3Missense obs/exp: 276 / 319.9Syn Z: 0.91

Background carrier burden — how many people carry a rare variant somewhere in MTMR6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 84

687 rare PASS variants

Rare truncating (LoF)

1 in 1,900

93 rare PASS variants

Rare synonymous (reference)

1 in 160

267 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MTMR6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 93	1 in 2,000
South Asian	~43k	1 in 78	1 in 4,600
Remaining (unassigned)	~30k	1 in 74	1 in 2,500
European (Finnish)	~27k	1 in 720	none seen
Admixed American	~22k	1 in 100	1 in 3,200
African / African American	~21k	1 in 97	1 in 1,500
East Asian	~20k	1 in 120	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 770	1 in 690
Middle Eastern	~2,884	1 in 88	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 14 coding exons well covered in gnomAD exomes; exons 2, 10, 13 marginal. Genomes: all 14.? see exons ↓