MTMR9

Chr 8

myotubularin related protein 9

Also known as: C8orf9, LIP-STYX, MTMR8

NCBI Gene: 66036 ENSG00000104643 UniProt: Q96QG7 OMIM: 606260

This protein acts as an adapter that enhances the catalytic activity of myotubularin-related phosphatases (MTMR6, MTMR7, MTMR8), which regulate phosphatidylinositol phospholipids involved in cellular processes including autophagy and apoptosis. The gene shows low constraint to loss-of-function variants (LOEUF 0.565), and pathogenic variants have not been definitively associated with human disease. Further research is needed to establish any clinical phenotypes resulting from MTMR9 mutations.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a myotubularin-related protein that is atypical to most other members of the myotubularin-related protein family because it has no dual-specificity phosphatase domain. The encoded protein contains a double-helical motif similar to the SET interaction domain, which is thought to have a role in the control of cell proliferation. In mouse, a protein similar to the encoded protein binds with MTMR7, and together they dephosphorylate phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.56

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.001

Z-score 3.46

OE 0.34 (0.21–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-2.33Z-score

OE missense 1.38 (1.27–1.49)

418 obs / 303.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.34 (0.21–0.56)

0≤0.351.4

Missense OE?1.38 (1.27–1.49)

0≤0.61.4

Synonymous OE?1.48

0≤1.21.6

LoF obs/exp: 11 / 32.2Missense obs/exp: 418 / 303.7Syn Z: -4.01

Background carrier burden — how many people carry a rare variant somewhere in MTMR9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 50

965 rare PASS variants

Rare truncating (LoF)

1 in 3,600

72 rare PASS variants

Rare synonymous (reference)

1 in 140

382 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MTMR9. 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 66	1 in 3,400
South Asian	~43k	1 in 45	1 in 1,800
Remaining (unassigned)	~30k	1 in 61	1 in 5,000
European (Finnish)	~27k	1 in 120	≈ 1 in 13,000
Admixed American	~22k	1 in 53	1 in 3,700
African / African American	~21k	1 in 56	1 in 3,800
East Asian	~20k	1 in 55	1 in 4,000
Ashkenazi Jewish	~13k	1 in 310	none seen
Middle Eastern	~2,884	1 in 53	none seen

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): 9 of 10 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 10.? see exons ↓