TPM1

Summary

TPM1 (tropomyosin 1, HGNC:12010) is a protein-coding gene on chromosome 15q22.2, encoding Tropomyosin alpha-1 chain (P09493). Binds to actin filaments in muscle and non-muscle cells.

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.

Source: NCBI Gene 7168 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypertrophic cardiomyopathy (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 28
• Clinical variants (ClinVar): 1,044 total — 9 pathogenic, 39 likely-pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001018005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12010
Approved symbol	TPM1
Name	tropomyosin 1
Location	15q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000140416
Ensembl biotype	protein_coding
OMIM	191010
Entrez	7168

Gene structure

Transcript identifiers

Ensembl transcripts: 65 — 43 protein_coding, 11 retained_intron, 10 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000267996, ENST00000288398, ENST00000317516, ENST00000334895, ENST00000357980, ENST00000358278, ENST00000403994, ENST00000404484, ENST00000558072, ENST00000558264, ENST00000558314, ENST00000558347, ENST00000558400, ENST00000558544, ENST00000558868, ENST00000558910, ENST00000559108, ENST00000559281, ENST00000559397, ENST00000559556, ENST00000559831, ENST00000560131, ENST00000560615, ENST00000560679, ENST00000560959, ENST00000560970, ENST00000560975, ENST00000561242, ENST00000561266, ENST00000561395, ENST00000561425, ENST00000610733, ENST00000644204, ENST00000651344, ENST00000651577, ENST00000651590, ENST00000651622, ENST00000651704, ENST00000705544, ENST00000714013, ENST00000714014, ENST00000714015, ENST00000714016, ENST00000714017, ENST00000893958, ENST00000893959, ENST00000893960, ENST00000940173, ENST00000940174, ENST00000940175, ENST00000940176, ENST00000940177, ENST00000942068, ENST00000942069, ENST00000942070, ENST00000942071, ENST00000942072, ENST00000942073, ENST00000942074, ENST00000942075, ENST00000942076, ENST00000942077, ENST00000942078, ENST00000942079, ENST00000942080

RefSeq mRNA: 40 — MANE Select: NM_001018005 NM_000366, NM_001018004, NM_001018005, NM_001018006, NM_001018007, NM_001018008, NM_001018020, NM_001301244, NM_001301289, NM_001330344, NM_001330346, NM_001330351, NM_001365776, NM_001365777, NM_001365778, NM_001365779, NM_001365780, NM_001365781, NM_001365782, NM_001407322, NM_001407323, NM_001407324, NM_001407325, NM_001407326, NM_001407327, NM_001407328, NM_001407329, NM_001407330, NM_001407331, NM_001407332, NM_001407333, NM_001407334, NM_001407335, NM_001407336, NM_001407337, NM_001407338, NM_001407340, NM_001407341, NM_001407342, NM_001407344

CCDS: CCDS10181, CCDS32262, CCDS32263, CCDS32264, CCDS45273, CCDS58368, CCDS58369, CCDS81891, CCDS81892, CCDS81894, CCDS86459, CCDS92009, CCDS92010, CCDS92011, CCDS92012, CCDS92013

Canonical transcript exons

ENST00000403994 — 10 exons

Exon	Start	End
ENSE00002555985	63065896	63066178
ENSE00002565172	63044027	63044152
ENSE00003506327	63060869	63060939
ENSE00003519887	63062576	63062645
ENSE00003554127	63056985	63057118
ENSE00003586543	63059563	63059680
ENSE00003790929	63062215	63062277
ENSE00004012902	63042747	63042943
ENSE00004022445	63061713	63061788
ENSE00004022446	63064064	63064142

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 424.4063 / max 12811.2806, expressed in 1809 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147067	373.8782	1434
147076	22.8501	1766
147082	3.3345	849
147077	3.3139	1150
147072	3.3095	792
147089	3.2331	792
147073	3.2135	991
147081	2.0463	643
147074	1.7129	826
147085	1.4501	569

Top tissues by expression

307 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.98	gold quality
heart right ventricle	UBERON:0002080	99.96	gold quality
myocardium	UBERON:0002349	99.95	gold quality
seminal vesicle	UBERON:0000998	99.94	gold quality
cardiac atrium	UBERON:0002081	99.94	gold quality
cardiac ventricle	UBERON:0002082	99.94	gold quality
heart left ventricle	UBERON:0002084	99.94	gold quality
apex of heart	UBERON:0002098	99.94	gold quality
right atrium auricular region	UBERON:0006631	99.94	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.93	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.91	gold quality
heart	UBERON:0000948	99.90	gold quality
lower esophagus	UBERON:0013473	99.90	gold quality
saphenous vein	UBERON:0007318	99.89	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.89	gold quality
smooth muscle tissue	UBERON:0001135	99.88	gold quality
cauda epididymis	UBERON:0004360	99.88	gold quality
blood vessel layer	UBERON:0004797	99.88	gold quality
biceps brachii	UBERON:0001507	99.86	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.86	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.86	gold quality
popliteal artery	UBERON:0002250	99.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.84	gold quality
tibial artery	UBERON:0007610	99.84	gold quality
sigmoid colon	UBERON:0001159	99.82	gold quality
artery	UBERON:0001637	99.82	gold quality
pancreatic ductal cell	CL:0002079	99.81	gold quality
right coronary artery	UBERON:0001625	99.81	gold quality
myometrium	UBERON:0001296	99.80	gold quality

Single-cell (SCXA)

Detected in 55 experiment(s), a significant marker in 43.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	4346.32
E-CURD-46	yes	3908.33
E-MTAB-10287	yes	3702.44
E-MTAB-6701	yes	3435.01
E-CURD-126	yes	3423.67
E-MTAB-10018	yes	3259.46
E-HCAD-23	yes	3038.23
E-MTAB-6108	yes	2969.51
E-MTAB-8205	yes	2639.58
E-CURD-98	yes	2524.78
E-HCAD-31	yes	2511.09
E-HCAD-36	yes	2318.26
E-CURD-122	yes	2116.76
E-CURD-88	yes	1693.46
E-MTAB-10432	yes	1513.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ARX, ATF2, ATF3, ATF5, ATF6, BATF3, BCL6, BHLHE41, CDX2, CEBPA, CEBPB, CEBPD, CEBPG, CEBPZ, CREB1, CREM, CTCF, CUX1, DBP, DLX2, DLX4, DNMT1, E2F1, E2F4, EGR1, EGR2, ELF1, EOMES, EPAS1, ESR1, ESR2, ESRRA, ETS1, FOS, FOXE1, FOXN1, FOXO1, FOXO3

miRNA regulators (miRDB)

56 targeting TPM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• requires an intact N-terminal coiled coil to interact with tropomodulin (PMID:11964245)
• These data, for the first time, show that hypermethylation of TM1 gene and chromatin remodeling are the predominant mechanisms by which TM1 expression is downregulated in breast cancer cells. (PMID:12065096)
• the expression of the human Hypertrophic Cardiomyopathy Mutant Tropomyosin in transgenic Mice results in myocardial contractile dysfunction (PMID:12169652)
• identified and demonstrated that the intracellular C terminus of polycystin-2 associates with a core regulatory protein of the actin cytoskeleton system, tropomyosin-1 (PMID:12527301)
• tropomyosin-1 is phosphorylated downstream of ERK, an event that modulates its interaction with actin (PMID:12686598)
• Loss of expression of TPM1 induces anoikis in primary breast tumors. (PMID:13679858)
• A previously described alpha-tropomyosin (TPM1) mutation (Asp175Asn) was found in 11% of cases. (PMID:15000344)
• proposed a hypothesis of pathogenetic changes caused by alpha-tropomyosin mutation Asp(175)Asn in familial hypertrophic cardiomyopathy on basis of changes in Ca(2+) handling as sensitive mechanism to compensate for alterations in sarcomeric structure. (PMID:15031138)
• HPRG binds to endothelial cell surface tropomyosin which at least partially mediates the antiangiogenic effects of HPRG (PMID:15269838)
• Effect of three point mutations is related to the overall stability of Tm as a whole, and that the mutations have only minor effects on the cooperative interactions among proteins that constitute the thin filament. (PMID:15479242)
• the role of tropomyosin is to facilitate the transmission of structural changes along the F-actin filament so that the monomers within a structural unit are able to interact with myosin (PMID:15695827)
• Epigenetic suppression of TPM1 may alter TGF-beta tumor suppressor function and contribute to metastatic properties of tumor cells. (PMID:15897890)
• alternative splicing of alpha-TM may be regulated by the antagonistic splicing regulators RBM4 and PTB (PMID:16260624)
• the familial dilated cardiomyopathy-causing mechanism of the E40K mutation may be accounted for by destabilization of the On state of the cardiac muscle thin filaments; the E54K mutation has a more complex effect on tropomyosin structure & function (PMID:17360712)
• in hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene, myocardial oxidative metabolism and FFA metabolism are increased and inversely related to LV hypertrophy at both the whole heart and regional level (PMID:17556170)
• study reports that DAP kinase promotes in vitro & in vivo phosphorylation of tropomyosin-1 on Ser283 & that this phosphorylation is essential for the H2O2-induced organization of the assembly of actin stress fibers in endothelial cells (PMID:17895359)
• data illustrate that, in general, dilated cardiomyopathy and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposite effects on the Ca2+ affinity of reconstituted thin filaments (PMID:17932326)
• tropomyosin 1 and cofilin play antagonistic roles within the contractile ring and that the balance between tropomyosin 1 and cofilin expression is important for cytokinesis. (PMID:18937355)
• TPM1 mutation was found involved in hypertrophic cardiomyopathy. (PMID:19035361)
• Dilated cardiomyopathy Glu40Lys and Glu54Lys mutations in alpha-tropomyosin induce a shifting of tropomyosin strands to the periphery of thin filament towards the “blocked” position and change the affinity of tropomyosin binding to actin. (PMID:19222994)
• miR-21 is an independent prognostic indicator for tongue squamous cell carcinomas (TSCC), and may play a role in TSCC development by inhibiting cancer cell apoptosis partly via TPM1 silencing. (PMID:19509158)
• data demonstrate specific changes caused by the dilated cardiomyopathy Glu54Lys mutation on the mutually dependent and concerted conformational changes in actin & myosin during the ATPase cycle, which are likely to underlie the observed functional effects (PMID:19646950)
• KRAS mutations correlate with expression of DCN and TPM1 in colorectal cancer. (PMID:19678923)
• functional analysis of TPM1kappa provides a possible mechanism for the consequences of the TM isoform switch observed in dilated cardiomyopathy and heart failure patients (PMID:20065163)
• A polymorphism in the TPM1 short isoform promoter region is predicted to alter transcription factor binding, alters gene expression and is associated with the metabolic syndrome. (PMID:20075843)
• Six different novel protein-altering variants of tropomyosin 1 were identified among 6 probands, and all of the nucleotide changes were considered possibly or likely disease causing. (PMID:20215591)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)
• TPM1 is a potential candidate disease-causing gene for isolated LVNC, especially in patients experiencing sudden death. (PMID:20965760)
• Patients with HCM attributable to D175N mutation of alpha-tropomyosin were studied by CMRI. LV maximal thickness by CMRI is the best parameter in differentiating between LVH due to mild-to-moderate hypertension and HCM attributable to a sarcomeric mutation. (PMID:21274714)
• results suggest that the E180G and D175N mutations reduce the affinity of tropomyosin for actin and also destabilize troponin binding to the actin thin filaments (PMID:21295541)
• The increased number of actively cycling cross bridges is the major cause of Tm mutation-related hypertrophic cardiomyopathy pathogenesis. (PMID:21320446)
• Asp175Asn and Glu180Gly mutations were found to shift tropomyosin strands further towards the open position and to change the affinity of tropomyosin for actin. (PMID:21376702)
• Conserved noncanonical residue Gly-126 confers instability to the middle part of the tropomyosin molecule. (PMID:21454502)
• identified 5 mutations in cardiac myosin-binding protein C (MYBPC3) and 2 mutations in alpha-tropomyosin (TPM1) in a cohort of unrelated adult probands with isolated left ventricular noncompaction cardiomyopathy (PMID:21551322)
• effect of Glu40Lys mutant alpha-tropomyosin on the mobility and rotation of subdomain-1 of actin and the SH1 helix of myosin subfragment-1 during the ATP hydrolysis cycle has been demonstrated (PMID:21741356)
• The hypoxia inducible factor-1 alpha/miR-21/tropomyosin 1 pathway may play a critical role in the pathogenesis of arteriosclerosis obliterans. (PMID:21817107)
• This is the first report of mutations in TPM1, MY L3, and MYL2 associated with primary, non-hypertrophied restrictive cardiomyopathy. (PMID:21823217)
• IgE recognition profile of profilins, PR-10 proteins and tropomyosin, were evaluated. (PMID:21949785)
• This work studied how the hypertrophic cardiomyopathy-causing Asp175Asn and Glu180Gly mutations in alpha-tropomyosin affect on actin-myosin interaction during the ATPase cycle (PMID:22155441)
• Functional and structural differences in three familial hypertrophic cardiomyopathy-related mutations in recombinant alpha-Tm were characterized using both conventional and modified in vitro motility assays and circular dichroism spectroscopy. (PMID:22187526)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	tpma	ENSDARG00000033683
danio_rerio	tpm1	ENSDARG00000087402
mus_musculus	Tpm1	ENSMUSG00000032366
rattus_norvegicus	Tpm1	ENSRNOG00000018184
drosophila_melanogaster	Tm1	FBGN0003721
drosophila_melanogaster	Tm2	FBGN0004117
caenorhabditis_elegans	lev-11	WBGENE00002978

Paralogs (3): TPM3 (ENSG00000143549), TPM4 (ENSG00000167460), TPM2 (ENSG00000198467)

Protein

Protein identifiers

Tropomyosin alpha-1 chain — P09493 (reviewed: P09493)

Alternative names: Alpha-tropomyosin, Tropomyosin-1

All UniProt accessions (27): P09493, A0A087WTJ7, A0A0K0K1I0, A0A0S2Z4G6, A0A494BZZ2, A0A494C0V8, A0A994J554, A0AAQ5BH66, A0AAQ5BH79, A0AAQ5BH85, A0AAQ5BH95, A0AAQ5BHC3, B7Z596, D9YZV4, D9YZV5, D9YZV7, F5H7S3, H0YK48, H0YKJ4, H0YKP3, H0YKX5, H0YL42, H0YL80, H0YLS7, H0YN06, H7BYY1, Q6ZN40

UniProt curated annotations — full annotation on UniProt →

Function. Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments.

Subunit / interactions. Homodimer. Heterodimer of an alpha (TPM1, TPM3 or TPM4) and a beta (TPM2) chain. Interacts with HRG (via the HRR domain); the interaction contributes to the antiangiogenic properties of the histidine/proline-rich region (HRR) of HRG. Interacts (via N-terminus) with LMOD2 (via N-terminus) and TMOD1 (via N-terminus).

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Detected in primary breast cancer tissues but undetectable in normal breast tissues in Sudanese patients. Isoform 1 is expressed in adult and fetal skeletal muscle and cardiac tissues, with higher expression levels in the cardiac tissues. Isoform 10 is expressed in adult and fetal cardiac tissues, but not in skeletal muscle.

Post-translational modifications. Phosphorylated at Ser-283 by DAPK1 in response to oxidative stress and this phosphorylation enhances stress fiber formation in endothelial cells.

Disease relevance. Cardiomyopathy, familial hypertrophic, 3 (CMH3) [MIM:115196] A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, dilated, 1Y (CMD1Y) [MIM:611878] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. The disease is caused by variants affecting the gene represented in this entry. Left ventricular non-compaction 9 (LVNC9) [MIM:611878] A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC9 is an autosomal dominant condition. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.

Miscellaneous. Incomplete sequence.

Similarity. Belongs to the tropomyosin family.

Isoforms (10)

UniProt ID	Names	Canonical?
P09493-1	1, Skeletal muscle, TPM1alpha	yes
P09493-2	2, Smooth muscle
P09493-3	3, Fibroblast, TM3
P09493-4	4
P09493-5	5
P09493-6	6, 10, TPM1kappa
P09493-7	7
P09493-8	8
P09493-9	9
P09493-10	10

RefSeq proteins (40): NP_000357, NP_001018004, NP_001018005, NP_001018006, NP_001018007, NP_001018008, NP_001018020, NP_001288173, NP_001288218, NP_001317273, NP_001317275, NP_001317280, NP_001352705, NP_001352706, NP_001352707, NP_001352708, NP_001352709, NP_001352710, NP_001352711, NP_001394251, NP_001394252, NP_001394253, NP_001394254, NP_001394255, NP_001394256, NP_001394257, NP_001394258, NP_001394259, NP_001394260, NP_001394261, NP_001394262, NP_001394263, NP_001394264, NP_001394265, NP_001394266, NP_001394267, NP_001394269, NP_001394270, NP_001394271, NP_001394273 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000533	Tropomyosin	Family

Pfam: PF00261

UniProt features (47 total): modified residue 15, splice variant 12, sequence variant 8, mutagenesis site 3, region of interest 2, sequence conflict 2, helix 2, chain 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
5KHT	X-RAY DIFFRACTION	1.5
3MUD	X-RAY DIFFRACTION	2.2
9ZBL	ELECTRON MICROSCOPY	2.79
9ZBP	ELECTRON MICROSCOPY	3.12
8ZB7	ELECTRON MICROSCOPY	3.19
8EFH	ELECTRON MICROSCOPY	3.3
8EFI	ELECTRON MICROSCOPY	3.4
8ENC	ELECTRON MICROSCOPY	3.6
6X5Z	ELECTRON MICROSCOPY	4.24
6KN8	ELECTRON MICROSCOPY	4.8
7UTI	ELECTRON MICROSCOPY	4.8
6KN7	ELECTRON MICROSCOPY	6.6
7UTL	ELECTRON MICROSCOPY	6.6
6UT2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09493-F1	91.67	0.75

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (15): 252, 261, 271, 283, 31, 213, 213, 51, 213, 213, 1, 45, 174, 186, 206

Mutagenesis-validated functional residues (3):

Position	Phenotype
15	impairs interaction with lmod2 and tmod1.
283	loss of phosphorylation and decreased formation of actin stress fibers.
283	increased formation of actin stress fibers.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-390522	Striated Muscle Contraction
R-HSA-445355	Smooth Muscle Contraction

MSigDB gene sets: 499 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, MODULE_52, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, PAX4_01, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, MODULE_493

GO Biological Process (18): positive regulation of heart rate by epinephrine (GO:0003065), regulation of muscle contraction (GO:0006937), cytoskeleton organization (GO:0007010), actin filament organization (GO:0007015), regulation of heart contraction (GO:0008016), regulation of cell shape (GO:0008360), muscle filament sliding (GO:0030049), negative regulation of cell migration (GO:0030336), ruffle organization (GO:0031529), cellular response to reactive oxygen species (GO:0034614), wound healing (GO:0042060), sarcomere organization (GO:0045214), positive regulation of cell adhesion (GO:0045785), positive regulation of stress fiber assembly (GO:0051496), ventricular cardiac muscle tissue morphogenesis (GO:0055010), cardiac muscle contraction (GO:0060048), negative regulation of vascular associated smooth muscle cell proliferation (GO:1904706), negative regulation of vascular associated smooth muscle cell migration (GO:1904753)

GO Molecular Function (9): actin binding (GO:0003779), structural constituent of cytoskeleton (GO:0005200), cytoskeletal protein binding (GO:0008092), structural constituent of muscle (GO:0008307), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (11): stress fiber (GO:0001725), cytosol (GO:0005829), cytoskeleton (GO:0005856), muscle thin filament tropomyosin (GO:0005862), actin filament (GO:0005884), actin cytoskeleton (GO:0015629), sarcomere (GO:0030017), bleb (GO:0032059), ruffle membrane (GO:0032587), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Muscle contraction	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
muscle contraction	2
heart contraction	2
structural molecule activity	2
cytoskeleton	2
protein binding	2
protein dimerization activity	2
positive regulation of heart rate by epinephrine-norepinephrine	1
regulation of heart rate by chemical signal	1
positive regulation of heart rate	1
regulation of muscle system process	1
organelle organization	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
regulation of blood circulation	1
regulation of cell morphogenesis	1
regulation of biological quality	1
actin-myosin filament sliding	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
plasma membrane bounded cell projection organization	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
response to wounding	1
tissue regeneration	1
myofibril assembly	1
actomyosin structure organization	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
cardiac ventricle morphogenesis	1
ventricular cardiac muscle tissue development	1
cardiac muscle tissue morphogenesis	1
striated muscle contraction	1
negative regulation of smooth muscle cell proliferation	1

Protein interactions and networks

STRING

2942 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPM1	TNNT2	P45379	969
TPM1	ACTC1	P04270	952
TPM1	TNNI3	P19429	930
TPM1	MYBPC3	Q14896	930
TPM1	MYH7	P12883	908
TPM1	MYL3	P08590	879
TPM1	TPM2	P06468	862
TPM1	TNNT1	P13805	860
TPM1	VCL	P18206	851
TPM1	CSRP3	P50461	821
TPM1	TPM3	P06753	806
TPM1	MYL2	P10916	788
TPM1	TTN	Q8WZ42	786
TPM1	ACTN2	P35609	773
TPM1	PRKAG2	Q9UGJ0	760

IntAct

164 interactions, top by confidence:

A	B	Type	Score
KXD1	TPM1	psi-mi:“MI:0915”(physical association)	0.800
TPM1	KXD1	psi-mi:“MI:0915”(physical association)	0.800
TPM1	MAD1L1	psi-mi:“MI:0915”(physical association)	0.780
PRKAG2	PRKAB2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TNNT1	TPM1	psi-mi:“MI:0915”(physical association)	0.670
TPM1	SYCE1	psi-mi:“MI:0915”(physical association)	0.670
TPM1	TNNT1	psi-mi:“MI:0915”(physical association)	0.670
SYCE1	TPM1	psi-mi:“MI:0915”(physical association)	0.670
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
TPM4	TPM3	psi-mi:“MI:0914”(association)	0.670

BioGRID (408): TPM1 (Affinity Capture-MS), TPM1 (Two-hybrid), TPM1 (Two-hybrid), TPM4 (Two-hybrid), MAD1L1 (Two-hybrid), TFPT (Two-hybrid), KXD1 (Two-hybrid), SYCE1 (Two-hybrid), C1orf216 (Two-hybrid), CAGE1 (Two-hybrid), TPM1 (Affinity Capture-MS), GOLGA3 (Affinity Capture-MS), TPM3 (Affinity Capture-MS), TPM4 (Affinity Capture-MS), TPM2 (Affinity Capture-MS)

ESM2 similar proteins: A1XQV4, A2V735, C5J049, O18416, O96764, O97192, P02561, P04268, P04692, P06753, P07951, P09491, P09493, P09495, P0DSM6, P0DSM7, P13104, P13105, P15846, P19352, P21107, P31816, P42637, P42639, P58771, P58772, P58773, P58774, P58775, P58776, P67936, P67937, P84335, Q01173, Q07068, Q1HPQ0, Q1HPU0, Q22866, Q23758, Q23939

Diamond homologs: A1XQV4, P02561, P04268, P04692, P06753, P07951, P09493, P13104, P13105, P19352, P21107, P42639, P58771, P58772, P58773, P58774, P58775, P58776, P67936, P67937, P84335, Q01173, Q07068, Q5KR47, Q5KR48, Q5KR49, Q9NDS0, O97162, P15846, Q22866, Q25632, Q8IT89, Q8WR63, Q95VA8, Q9NAS5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
DAPK1	“up-regulates activity”	TPM1	phosphorylation
PIK3CA	“up-regulates activity”	TPM1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Striated Muscle Contraction	5	15.3×	4e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	10.7×	3e-03
Signaling by ALK fusions and activated point mutants	6	8.9×	8e-03
Signaling by Interleukins	9	5.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1044 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	39
Uncertain significance	470
Likely benign	339
Benign	57

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1067773	NM_001018005.2(TPM1):c.710C>G (p.Thr237Ser)	Pathogenic
12455	NM_001018005.2(TPM1):c.539A>G (p.Glu180Gly)	Pathogenic
12456	NM_001018005.2(TPM1):c.523G>A (p.Asp175Asn)	Pathogenic
181684	NM_001018005.2(TPM1):c.276C>G (p.Ile92Met)	Pathogenic
31884	NM_001018005.2(TPM1):c.688G>A (p.Asp230Asn)	Pathogenic
31901	NM_001018005.2(TPM1):c.742A>G (p.Lys248Glu)	Pathogenic
3340563	NM_001018005.2(TPM1):c.497C>T (p.Ala166Val)	Pathogenic
4277488	NM_001018005.2(TPM1):c.281T>A (p.Leu94Gln)	Pathogenic
4763869	NM_001018005.2(TPM1):c.553C>T (p.Leu185Phe)	Pathogenic
1002513	NM_001018005.2(TPM1):c.538G>A (p.Glu180Lys)	Likely pathogenic
1012347	NM_001018005.2(TPM1):c.598G>C (p.Val200Leu)	Likely pathogenic
1721605	NM_001018005.2(TPM1):c.541G>C (p.Glu181Gln)	Likely pathogenic
1727219	NM_001018005.2(TPM1):c.656A>T (p.Asp219Val)	Likely pathogenic
177659	NM_001018005.2(TPM1):c.559G>C (p.Glu187Gln)	Likely pathogenic
177896	NM_001018005.2(TPM1):c.416A>T (p.Glu139Val)	Likely pathogenic
228297	NM_001018005.2(TPM1):c.496G>A (p.Ala166Thr)	Likely pathogenic
242912	NM_001018005.2(TPM1):c.412G>A (p.Glu138Lys)	Likely pathogenic
254158	NM_001018005.2(TPM1):c.519G>C (p.Glu173Asp)	Likely pathogenic
264474	NM_001018005.2(TPM1):c.250G>A (p.Asp84Asn)	Likely pathogenic
2833135	NM_001018005.2(TPM1):c.433G>A (p.Glu145Lys)	Likely pathogenic
2834088	NM_001018005.2(TPM1):c.161A>C (p.Glu54Ala)	Likely pathogenic
3075681	NM_001018005.2(TPM1):c.430C>G (p.Gln144Glu)	Likely pathogenic
31876	NM_001018005.2(TPM1):c.184G>C (p.Glu62Gln)	Likely pathogenic
31880	NM_001018005.2(TPM1):c.539A>T (p.Glu180Val)	Likely pathogenic
3381178	NM_001018005.2(TPM1):c.296T>C (p.Leu99Ser)	Likely pathogenic
3460488	NM_001018005.2(TPM1):c.461T>C (p.Ile154Thr)	Likely pathogenic
370040	NM_001018005.2(TPM1):c.686C>T (p.Ser229Phe)	Likely pathogenic
370041	NM_001018005.2(TPM1):c.388A>G (p.Ile130Val)	Likely pathogenic
3775259	NM_001018005.2(TPM1):c.791A>G (p.Lys264Arg)	Likely pathogenic
3780971	NM_001018005.2(TPM1):c.42C>G (p.Asp14Glu)	Likely pathogenic

SpliceAI

1801 predictions. Top by Δscore:

Variant	Effect	Δscore
15:63043660:ACCC:A	acceptor_gain	1.0000
15:63044148:CCGAT:C	donor_gain	1.0000
15:63044150:GAT:G	donor_gain	1.0000
15:63044151:AT:A	donor_gain	1.0000
15:63044151:ATGTA:A	donor_loss	1.0000
15:63044152:TG:T	donor_loss	1.0000
15:63044153:G:GG	donor_gain	1.0000
15:63044153:G:T	donor_loss	1.0000
15:63044154:T:TC	donor_loss	1.0000
15:63056980:CCTA:C	acceptor_loss	1.0000
15:63056981:CTA:C	acceptor_loss	1.0000
15:63056983:A:AG	acceptor_gain	1.0000
15:63056983:A:C	acceptor_loss	1.0000
15:63056983:AG:A	acceptor_gain	1.0000
15:63056983:AGGCT:A	acceptor_gain	1.0000
15:63056984:G:GG	acceptor_gain	1.0000
15:63056984:GG:G	acceptor_gain	1.0000
15:63056984:GGCT:G	acceptor_gain	1.0000
15:63056984:GGCTG:G	acceptor_gain	1.0000
15:63057087:G:GT	donor_gain	1.0000
15:63057115:AGAG:A	donor_gain	1.0000
15:63057115:AGAGG:A	donor_loss	1.0000
15:63057116:GAG:G	donor_gain	1.0000
15:63057116:GAGG:G	donor_gain	1.0000
15:63057116:GAGGT:G	donor_loss	1.0000
15:63057117:AGGTG:A	donor_loss	1.0000
15:63057119:G:GG	donor_gain	1.0000
15:63057119:GTGAG:G	donor_loss	1.0000
15:63057120:T:A	donor_loss	1.0000
15:63059561:A:AG	acceptor_gain	1.0000

AlphaMissense

1877 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:63059639:G:C	A151P	1.000
15:63059660:G:C	A158P	1.000
15:63042861:T:C	L11P	0.999
15:63057016:G:C	R91P	0.999
15:63057025:T:C	L94P	0.999
15:63057061:T:C	L106P	0.999
15:63057069:G:C	A109P	0.999
15:63057090:G:C	A116P	0.999
15:63057102:G:C	A120P	0.999
15:63059631:T:C	L148P	0.999
15:63059651:G:C	A155P	0.999
15:63060882:T:C	L169P	0.999
15:63060923:G:C	A183P	0.999
15:63062588:G:C	A239P	0.999
15:63062597:G:C	A242P	0.999
15:63056985:G:C	A81P	0.998
15:63057007:T:C	L88P	0.998
15:63057048:G:C	A102P	0.998
15:63057058:G:C	R105P	0.998
15:63057082:T:C	L113P	0.998
15:63059588:G:C	A134P	0.998
15:63059652:C:A	A155D	0.998
15:63059667:G:C	R160P	0.998
15:63060876:G:C	R167P	0.998
15:63060903:T:C	L176P	0.998
15:63062270:T:C	L232P	0.998
15:63062576:G:C	A235P	0.998
15:63064112:T:C	L274P	0.998
15:63042881:G:C	A18P	0.997
15:63042893:G:C	A22P	0.997

dbSNP variants (sampled 300 via entrez): RS1000056465 (15:63063699 T>C,G), RS1000090871 (15:63063974 G>A,C), RS1000253641 (15:63041699 C>T), RS1000317298 (15:63069393 C>T), RS1000378084 (15:63049699 T>C), RS1000389851 (15:63041970 C>T), RS1000570654 (15:63048059 G>A), RS1000755020 (15:63071227 C>T), RS1000848597 (15:63071643 A>G), RS1000964621 (15:63043259 C>T), RS1001080818 (15:63052016 A>T), RS1001233325 (15:63056113 G>A), RS1001307424 (15:63057306 A>G), RS1001363410 (15:63065552 C>G), RS1001384371 (15:63044595 C>G,T)

Disease associations

OMIM: gene MIM:191010 | disease phenotypes: MIM:611878, MIM:115196, MIM:192600, MIM:604169, MIM:108800, MIM:265150, MIM:614676

GenCC curated gene-disease

Disease	Classification	Inheritance
hypertrophic cardiomyopathy 3	Definitive	Autosomal dominant
dilated cardiomyopathy 1Y	Strong	Autosomal dominant
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
left ventricular noncompaction	Supportive	Autosomal dominant
arrhythmogenic right ventricular cardiomyopathy	No Known Disease Relationship	Autosomal dominant

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dilated cardiomyopathy 1Y	Moderate	AD
hypertrophic cardiomyopathy	Definitive	AD
arrhythmogenic right ventricular cardiomyopathy	No Known Disease Relationship	AD

Mondo (15): hypertrophic cardiomyopathy (MONDO:0005045), cardiomyopathy (MONDO:0004994), dilated cardiomyopathy 1Y (MONDO:0012744), hypertrophic cardiomyopathy 3 (MONDO:0007267), dilated cardiomyopathy (MONDO:0005021), familial hypertrophic cardiomyopathy (MONDO:0024573), familial cardiomyopathy (MONDO:0005217), left ventricular noncompaction (MONDO:0018901), left ventricular noncompaction 9 (MONDO:0800346), hypertrophic cardiomyopathy 1 (MONDO:0008647), atrial septal defect 1 (MONDO:0007172), pulmonary atresia-intact ventricular septum syndrome (MONDO:0009931), hypertrophic cardiomyopathy 21 (MONDO:0013852), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), (MONDO:0015470)

Orphanet (9): Rare hypertrophic cardiomyopathy (Orphanet:217569), Rare cardiomyopathy (Orphanet:167848), Familial isolated dilated cardiomyopathy (Orphanet:154), Left ventricular noncompaction (Orphanet:54260), Dilated cardiomyopathy (Orphanet:217604), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Interatrial communication (Orphanet:1478), Pulmonary atresia-intact ventricular septum syndrome (Orphanet:1208), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000969	Edema
HP:0001635	Congestive heart failure
HP:0001639	Hypertrophic cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001653	Mitral regurgitation
HP:0001727	Thromboembolic stroke
HP:0002875	Exertional dyspnea
HP:0003198	Myopathy
HP:0003457	EMG abnormality
HP:0003577	Congenital onset
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0003623	Neonatal onset
HP:0004756	Ventricular tachycardia
HP:0005110	Atrial fibrillation
HP:0010316	Ebstein anomaly of the tricuspid valve
HP:0011461	Fetal onset
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0011664	Left ventricular noncompaction cardiomyopathy
HP:0011675	Arrhythmia
HP:0012378	Fatigue
HP:0012764	Orthopnea
HP:0025169	Left ventricular systolic dysfunction
HP:0033755	Increased left ventricular end-diastolic volume
HP:0100578	Lipoatrophy

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000497_15	Mean platelet volume	2.000000e-08
GCST001337_46	Platelet count	4.000000e-10
GCST001628_31	Orofacial clefts	8.000000e-07
GCST003652_4	Parkinson’s disease (familial, age at onset)	9.000000e-11
GCST004599_178	Mean platelet volume	4.000000e-53
GCST004603_234	Platelet count	1.000000e-35
GCST004616_61	Platelet distribution width	7.000000e-34
GCST006479_98	Diverticular disease	2.000000e-06
GCST007096_47	Pulse pressure	3.000000e-09
GCST008075_186	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5.000000e-09
GCST008075_79	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-08
GCST008084_202	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-11
GCST008084_80	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-10
GCST008085_183	HDL cholesterol levels in current drinkers	1.000000e-06
GCST008747_157	Estimated glomerular filtration rate	3.000000e-09
GCST009642_5	Impaired insulin sensitivity in response to n-3 PUFA supplementation	8.000000e-06
GCST010002_172	Refractive error	6.000000e-36
GCST010241_130	Apolipoprotein A1 levels	4.000000e-24
GCST010242_405	HDL cholesterol levels	3.000000e-20
GCST010244_124	Triglyceride levels	1.000000e-13
GCST010991_21	Parkinson’s disease	2.000000e-06
GCST90002384_384	Hemoglobin	4.000000e-09
GCST90002395_173	Mean platelet volume	4.000000e-112
GCST90002395_174	Mean platelet volume	4.000000e-18
GCST90002401_91	Platelet distribution width	1.000000e-79
GCST90002402_163	Platelet count	7.000000e-61
GCST90002402_164	Platelet count	1.000000e-10
GCST90002406_386	Reticulocyte fraction of red cells	3.000000e-10

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004847	age at onset
EFO:0007984	platelet component distribution width
EFO:0009959	diverticular disease
EFO:0005763	pulse pressure measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004471	insulin sensitivity measurement
EFO:0009131	response to polyunsaturated fatty acid supplementation
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004530	triglyceride measurement
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
C567507	Cardiomyopathy, Dilated, 1y (supp.)
C566170	Cardiomyopathy, Familial Hypertrophic, 3 (supp.)
C562832	Pulmonary Atresia with Intact Ventricular Septum (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4295705 (SINGLE PROTEIN), CHEMBL5465391 (CHIMERIC PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	6
Doxorubicin	affects expression, increases expression, affects response to substance	4
Valproic Acid	affects expression, decreases expression, increases expression	4
Particulate Matter	increases abundance, decreases expression	4
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	3
Dexamethasone	affects cotreatment, decreases expression	3
Estradiol	increases expression, increases reaction, affects cotreatment	3
Ethinyl Estradiol	affects expression, decreases expression	3
methylmercuric chloride	decreases expression, increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases expression	2
cobaltous chloride	decreases expression	2
entinostat	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	decreases expression	2
Smoke	increases expression, decreases expression, increases abundance	2
1-Methyl-3-isobutylxanthine	decreases expression, affects cotreatment	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression, increases methylation	2
Genistein	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
propionaldehyde	increases expression	1
glycidyl methacrylate	increases expression	1
methylselenic acid	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118945	Binding	Binding affinity to TPM1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

7 cell lines: 3 induced pluripotent stem cell, 3 cancer cell line, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0JT	YCMi005-A	Induced pluripotent stem cell	Female
CVCL_A7RW	WAe009-A-61	Embryonic stem cell	Female
CVCL_C1TV	KSCBi018-A-1	Induced pluripotent stem cell	Male
CVCL_C9JE	CHOPi013-A	Induced pluripotent stem cell	Male
CVCL_D1ZE	Abcam A-549 TPM1 KO	Cancer cell line	Male
CVCL_D2DF	Abcam HCT 116 TPM1 KO	Cancer cell line	Male
CVCL_D2PB	Abcam THP-1 TPM1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

258 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
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