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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TIMM44
translocase of inner mitochondrial membrane 44
Chromosome 19 · 19p13.2
NCBI Gene: 10469Ensembl: ENSG00000104980.9HGNC: HGNC:17316UniProt: O43615
117PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmitochondrionmitochondrial inner membranemitochondrial matrixneurodegenerative diseaseParkinson diseaselysosomal storage diseasemultiple sclerosis
✦AI Summary

TIMM44 is an essential component of the PAM (presequence translocase-associated motor) complex within the inner mitochondrial membrane, functioning as a critical regulator of mitochondrial protein import. TIMM44 recruits mitochondrial HSP70 to the TIM23 translocase complex, driving ATP-dependent translocation of transit peptide-containing proteins into the mitochondrial matrix 1. The protein directly interacts with ANT (adenine nucleotide translocator) and regulates peptide import through TIM23 1, positioning it as a key node in mitochondrial homeostasis. TIMM44 dysfunction has significant disease implications across multiple pathologies. In heart failure patients, TIMM44 expression is substantially downregulated as part of widespread mitochondrial quality control deficiency 2. Conversely, TIMM44 is upregulated in cancer contexts: elevated expression correlates with poor prognosis in glioma 3, and pharmacological TIMM44 inhibition (MB-10) suppresses bladder cancer cell growth through mitochondrial depolarization and ATP depletion 4. TIMM44 is also required for angiogenesis in endothelial cells; its silencing or pharmacological blockade impairs mitochondrial function and inhibits capillary tube formation both in vitro and in vivo 5. In metabolic disease, TIMM44 overexpression in adipose tissue protects against type 2 diabetes by promoting mitochondrial fusion and enhancing insulin sensitivity 6. These findings establish TIMM44 as a versatile therapeutic target with potential across cancer, cardiovascular, metabolic, and vascular diseases.

Sources cited
1
TIMM44 interacts with ANT and regulates TIM23 function; ANT modulates TIM23 indirectly via interaction with TIM44
PMID: 31618756
2
TIMM44 expression is downregulated in heart failure patients with ischemic and dilated cardiomyopathy
PMID: 37403271
3
TIMM44 is upregulated in glioma tissues and correlates with poor overall survival; TIMM44 depletion inhibits glioma cell viability and proliferation
PMID: 36438483
4
TIMM44 is elevated in bladder cancer; MB-10 TIMM44 blocker induces apoptosis, mitochondrial depolarization, and ATP reduction in cancer cells but not normal epithelial cells
PMID: 38467612
5
TIMM44 silencing and pharmacological blockade inhibit endothelial cell proliferation, migration, and angiogenesis through mitochondrial dysfunction
PMID: 37147302
6
TIMM44 overexpression protects against type 2 diabetes and obesity by promoting mitochondrial fusion and enhancing insulin sensitivity
PMID: 25749183
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.43Moderate
Parkinson diseaseOpen Targets
0.37Weak
Alzheimer diseaseOpen Targets
0.37Weak
lysosomal storage diseaseOpen Targets
0.37Weak
multiple sclerosisOpen Targets
0.37Weak
metabolic diseaseOpen Targets
0.14Weak
gliomaOpen Targets
0.08Suggestive
urinary bladder carcinomaOpen Targets
0.07Suggestive
diabetes mellitusOpen Targets
0.06Suggestive
MODYOpen Targets
0.06Suggestive
type 2 diabetes mellitusOpen Targets
0.06Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.05Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.04Suggestive
hyperproinsulinemiaOpen Targets
0.04Suggestive
Glycogen storage disease due to hepatic glycogen synthase deficiencyOpen Targets
0.04Suggestive
glycogen storage disorder due to hepatic glycogen synthase deficiencyOpen Targets
0.04Suggestive
cancerOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.02Suggestive
breast cancerOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HSPA4Protein interaction100%TIMM10Protein interaction97%HSPA9Protein interaction97%TOMM70Protein interaction97%TOMM40Protein interaction97%BCS1LProtein interaction96%
Tissue Expression6 tissues
Liver
100%
Heart
97%
Ovary
79%
Bone Marrow
60%
Lung
57%
Brain
39%
Gene Interaction Network
Click a node to explore
TIMM44HSPA4TIMM10HSPA9TOMM70TOMM40BCS1L
PROTEIN STRUCTURE
Preparing viewer…
PDB2CW9 · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.76LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.58 [0.44–0.76]
RankingsWhere TIMM44 stands among ~20K protein-coding genes
  • #4,067of 20,598
    Most Researched117 · top quartile
  • #6,053of 17,882
    Most Constrained (LOEUF)0.76
Genes detectedTIMM44
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The ADP/ATP translocase drives mitophagy independent of nucleotide exchange.
PMID: 31618756
Nature · 2019
1.00
2
A first-in-class TIMM44 blocker inhibits bladder cancer cell growth.
PMID: 38467612
Cell Death Dis · 2024
0.90
3
Heart failure in patients is associated with downregulation of mitochondrial quality control genes.
PMID: 37403271
Eur J Clin Invest · 2023
0.80
4
The mitochondrial protein TIMM44 is required for angiogenesis in vitro and in vivo.
PMID: 37147302
Cell Death Dis · 2023
0.70
5
Endogenous interactomes of MFN1 and MFN2 provide novel insights into interorganelle communication and autophagy.
PMID: 39675054
Autophagy · 2025
0.60