TMOD2

Chr 15

tropomodulin 2

Also known as: N-TMOD, NTMOD

NCBI Gene: 29767 ENSG00000128872 UniProt: Q9NZR1 OMIM: 602928

This gene encodes a neuronal-specific member of the tropomodulin family of actin-regulatory proteins. The encoded protein caps the pointed end of actin filaments preventing both elongation and depolymerization. The capping activity of this protein is dependent on its association with tropomyosin. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2008]

OMIM Research

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

0.68

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.020

Z-score 2.55

OE 0.34 (0.19–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.39Z-score

OE missense 0.92 (0.81–1.04)

169 obs / 183.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.19–0.68)

0≤0.351.4

Missense OE?0.92 (0.81–1.04)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 6 / 17.5Missense obs/exp: 169 / 183.9Syn Z: 0.78

Background carrier burden — how many people carry a rare variant somewhere in TMOD2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

421 rare PASS variants

Rare truncating (LoF)

1 in 4,100

50 rare PASS variants

Rare synonymous (reference)

1 in 610

135 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMOD2. 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 230	1 in 8,000
South Asian	~43k	1 in 150	1 in 3,000
Remaining (unassigned)	~30k	1 in 190	1 in 1,400
European (Finnish)	~27k	1 in 500	1 in 1,900
Admixed American	~22k	1 in 150	1 in 1,600
African / African American	~21k	1 in 210	1 in 3,400
East Asian	~20k	1 in 140	1 in 1,400
Ashkenazi Jewish	~13k	1 in 350	none seen
Middle Eastern	~2,884	1 in 130	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): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓