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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TMOD4
tropomodulin 4
Chromosome 1 · 1q21.3
NCBI Gene: 29765Ensembl: ENSG00000163157.16HGNC: HGNC:11874UniProt: Q9NZQ9
17PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
striated muscle thin filamentprotein bindingmuscle contractionactin filament organizationmyocardial infarctioncoronary artery diseaseIschemic strokeliver cancer
✦AI Summary

TMOD4 (tropomodulin 4) is an actin-capping protein that blocks elongation and depolymerization of actin filaments at the pointed end, contributing to thin filament length regulation and sarcomere assembly in muscle 1. TMOD4 is predominantly expressed in muscle tissues 1 and functions redundantly with leiomodin 3 during skeletal myofibrillogenesis; loss of either protein disrupts sarcomere assembly, though compensatory upregulation can restore function 2. Notably, TMOD1 appears to be the primary regulator of thin filament length in adult skeletal muscle, with TMOD4 being largely dispensable for this function under normal conditions 3. Beyond muscle function, TMOD4 has unexpected roles in metabolic disease. The LEPIS-HuR-TMOD4 regulatory axis controls hepatic cholesterol homeostasis by affecting PCSK9 and LDLR expression, with TMOD4 overexpression accelerating atherosclerosis in mice 4. In liver cancer, BFSP1 directly interacts with TMOD4 to promote aerobic glycolysis and tumor progression through m6A-mediated regulation 5. Genetic variants in TMOD4 are associated with susceptibility to early-onset myocardial infarction, hypertension, and chr1 kidney disease 6, suggesting TMOD4 has broader cardiovascular and metabolic significance beyond skeletal muscle physiology.

Sources cited
1
TMOD4 regulates hepatic cholesterol homeostasis and atherosclerosis progression through PCSK9 and LDLR via the LEPIS-HuR axis
PMID: 38663275
2
TMOD4 genomic structure and organization with unusual intergenic splicing involving YL-1
PMID: 11716785
3
TMOD4 is among the most downregulated genes in cultured myotubes compared to skeletal muscle tissue
PMID: 20175888
4
TMOD4 directly interacts with BFSP1 and promotes aerobic glycolysis and liver cancer progression
PMID: 40097750
5
TMOD4 is a muscle-specific actin-capping protein and candidate gene for limb girdle muscular dystrophy 1B
PMID: 10662549
6
TMOD4 and leiomodin 3 have overlapping, redundant functions during skeletal myofibrillogenesis
PMID: 25431137
7
TMOD4 variants are associated with susceptibility to early-onset myocardial infarction, hypertension, and chronic kidney disease
PMID: 30226566
8
TMOD1 is the primary direct regulator of thin filament length in skeletal muscle; TMOD4 is largely dispensable for this function
PMID: 26586224
Disease Associationsⓘ20
myocardial infarctionOpen Targets
0.27Weak
coronary artery diseaseOpen Targets
0.25Weak
Ischemic strokeOpen Targets
0.25Weak
liver cancerOpen Targets
0.04Suggestive
Decreased total leukocyte countOpen Targets
0.04Suggestive
hypertensionOpen Targets
0.04Suggestive
chronic kidney diseaseOpen Targets
0.04Suggestive
neutropeniaOpen Targets
0.03Suggestive
atherosclerosisOpen Targets
0.02Suggestive
malariaOpen Targets
0.01Suggestive
obstructive sleep apneaOpen Targets
0.01Suggestive
heart failureOpen Targets
0.01Suggestive
male infertilityOpen Targets
0.01Suggestive
gliomaOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
cardiac hypertrophyOpen Targets
0.01Suggestive
inherited lipid metabolism disorderOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
muscular diseaseOpen Targets
0.01Suggestive
urinary bladder carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ANK2Protein interaction98%ANK1Protein interaction98%MYL1Protein interaction97%MTPNProtein interaction96%ANK3Protein interaction96%ADD1Protein interaction95%
Tissue Expression4 tissues
Liver
0%
Ovary
0%
Bone Marrow
0%
Lung
0%
Gene Interaction Network
Click a node to explore
TMOD4ANK2ANK1MYL1MTPNANK3ADD1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9NZQ9
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.00LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.75 [0.57–1.00]
RankingsWhere TMOD4 stands among ~20K protein-coding genes
  • #15,156of 20,598
    Most Researched17
  • #9,666of 17,882
    Most Constrained (LOEUF)1.00
Genes detectedTMOD4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The LEPIS-HuR-TMOD4 axis regulates hepatic cholesterol homeostasis and accelerates atherosclerosis.
PMID: 38663275
Atherosclerosis · 2024
1.00
2
Genomic organization of Tropomodulins 2 and 4 and unusual intergenic and intraexonic splicing of YL-1 and Tropomodulin 4.
PMID: 11716785
BMC Genomics · 2001
0.90
3
Comparative gene expression profiling between human cultured myotubes and skeletal muscle tissue.
PMID: 20175888
BMC Genomics · 2010
0.80
4
M6A-modified BFSP1 induces aerobic glycolysis to promote liver cancer growth and metastasis through upregulating tropomodulin 4.
PMID: 40097750
Mol Biomed · 2025
0.70
5
Sequencing, expression analysis, and mapping of three unique human tropomodulin genes and their mouse orthologs.
PMID: 10662549
Genomics · 2000
0.60