TPM1

Chr 15

tropomyosin 1

Also known as: C15orf13, CMD1Y, CMH3, HEL-S-265, HTM-alpha, LVNC9, TMSA

NCBI Gene: 7168 ENSG00000140416 UniProt: P09493

This gene is a member of the tropomyosin family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosin is composed of two alpha-helical chains arranged as a coiled-coil. It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments. The encoded protein is one type of alpha helical chain that forms the predominant tropomyosin of striated muscle, where it also functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. In smooth muscle and non-muscle cells, alternatively spliced transcript variants encoding a range of isoforms have been described. Mutations in this gene are associated with type 3 familial hypertrophic cardiomyopathy and dilated cardiomyopathy 1Y. [provided by RefSeq, Jun 2022]

GeneReviews Research

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCardiomyopathy, familial hypertrophic, 3

UniProtCardiomyopathy, dilated, 1Y

UniProtLeft ventricular non-compaction 9

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — TPM1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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?

0.78LOEUF

pLI 0.001

Z-score 2.25

OE 0.43 (0.25–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.87Z-score

OE missense 0.35 (0.28–0.44)

53 obs / 152.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.43 (0.25–0.78)

0≤0.351.4

Missense OE?0.35 (0.28–0.44)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 8 / 18.4Missense obs/exp: 53 / 152.7Syn Z: -1.24

Background carrier burden — how many people carry a rare variant somewhere in TPM1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

476 rare PASS variants

Rare truncating (LoF)

1 in 950

108 rare PASS variants

Rare synonymous (reference)

1 in 140

285 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TPM1. 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 250	1 in 2,000
South Asian	~43k	1 in 160	1 in 2,000
Remaining (unassigned)	~30k	1 in 120	1 in 620
European (Finnish)	~27k	1 in 280	1 in 2,000
Admixed American	~22k	1 in 200	1 in 490
African / African American	~21k	1 in 160	1 in 2,500
East Asian	~20k	1 in 160	1 in 1,500
Ashkenazi Jewish	~13k	≈ 1 in 3,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 150	≈ 1 in 930

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 4 marginal. Genomes: all 10.? see exons ↓