TPM1

tropomyosin 1

4 disorders 2 untyped 2 causative 15q22.2 gene with protein product

HGNC:12010 Monarch NCBI Gene 7168 ENSG00000140416 UniProt P09493 OMIM 191010

Previous symbols: C15orf13, CMH3.

Normal function · from ai-gene-review (P09493, commit 79fe13b38970) · AI-generated, not KB evidence

TPM1 (Tropomyosin 1) is a coiled-coil actin-binding protein with 10 tissue-specific isoforms. ISOFORM BIOLOGY: (1) Isoform 1 (TPM1alpha, P09493-1) is expressed in SKELETAL MUSCLE; (2) Isoform 2 is SMOOTH MUSCLE-specific; (3) Isoform 3 (TM3) is the FIBROBLAST/cytoskeletal form; (4) Isoform 6 (TPM1kappa) is CARDIAC-specific. UniProt states "Isoform 1 is expressed in adult and fetal skeletal muscle and cardiac tissues. Isoform 10 is expressed in adult and fetal cardiac tissues, but not in skeletal muscle." Muscle isoforms regulate actin-myosin interaction in sarcomeres; cytoskeletal isoforms organize non-muscle actin. DISEASE: Mutations cause cardiomyopathy (CMH3, CMD1Y) affecting sarcomere function. Annotations for "muscle contraction" and "sarcomere" apply primarily to muscle isoforms, while "cytoskeleton organization" applies more to non-muscle isoforms.

Actin filament binding is the fundamental molecular function of all TPM1 isoforms. Tropomyosin dimers bind along the length of actin filaments in both muscle (thin filaments) and non-muscle (stress fibers) cells, stabilizing actin filaments and regulating their interactions with other proteins.

molecular function: actin filament binding · directly involved in: actin filament organization · locations: actin filament

ISOFORM-SPECIFIC (Cardiac isoforms): Cardiac muscle contraction is a core function of striated muscle isoforms (TPM1alpha, TPM1kappa). TPM1 regulates calcium-dependent actin-myosin interaction via the troponin complex. Mutations cause cardiomyopathy (CMH3, CMD1Y).

molecular function: actin filament binding · directly involved in: cardiac muscle contraction; regulation of muscle contraction · locations: sarcomere · in complex: muscle thin filament tropomyosin

ISOFORM-SPECIFIC (Cytoskeletal isoforms): Non-muscle TPM1 isoforms (e.g., TM3) bind actin filaments in stress fibers and contribute to cytoskeletal organization, cell shape regulation, and cell motility.

molecular function: actin filament binding · directly involved in: actin filament organization; positive regulation of stress fiber assembly · locations: stress fiber

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Dilated Cardiomyopathy 1Y	causative	mechanism: TPM1 Missense Variant animal model: D230N-Tm transgenic mouse
Hypertrophic Cardiomyopathy 3	causative	mechanism: Alpha-Tropomyosin Thin Filament Regulatory Defect
Dilated Cardiomyopathy	untyped Pathogenic Variants	mechanism: Sarcomeric and Cytoskeletal Dysfunction
Hypertrophic Cardiomyopathy	untyped Pathogenic Variants	mechanism: Sarcomere Protein Mutations

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
hypertrophic cardiomyopathy MONDO:0005045	AD	Definitive 2023-12-18	Hypertrophic Cardiomyopathy untyped
dilated cardiomyopathy 1Y MONDO:0012744	AD	Moderate 2026-03-04	Dilated Cardiomyopathy 1Y causative
arrhythmogenic right ventricular cardiomyopathy MONDO:0016587	AD	No Known Disease Relationship 2019-09-13	arrhythmogenic right ventricular cardiomyopathy not named

Mechanism modules · computed from kb/

cardiomyopathy_maladaptive_remodeling via Hypertrophic Cardiomyopathy 3

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.