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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TMC3
transmembrane channel like 3
Chromosome 15 · 15q25.1
NCBI Gene: 342125Ensembl: ENSG00000188869.13HGNC: HGNC:22995UniProt: Q7Z5M5
12PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolmechanosensitive monoatomic ion channel activityplasma membranemonoatomic ion transmembrane transportAbnormality of the skeletal systemneurodegenerative diseasepathological myopiacholelithiasis
✦AI Summary

TMC3 (transmembrane channel-like 3) is a putative ion channel component with incompletely characterized molecular function 1. TMC3 exhibits mechanosensitive ion channel activity and localizes to the plasma membrane and cytosol 1. In cardiac fibroblasts, TMC3 is the most highly expressed member of the TMC protein family 1, suggesting specialized roles in mechanotransduction within cardiac tissue. TMC3 has emerging relevance in multiple disease contexts. In renal clear cell carcinoma, TMC3 expression significantly correlates with overall survival and positively associates with immune cell infiltration and checkpoint gene expression 2. In acute kidney injury, the TMC3-derived long non-coding RNA TMC3-AS1 negatively regulates IL-10 expression and promotes inflammatory pathways through miR-148a-3p regulation of Wnt5a, contributing to autophagy and pyroptosis 34. Notably, TMC3-AS1 silencing alleviates LPS-induced kidney injury 4. Genome-wide association studies identified TMC3 within a locus associated with longitudinal decline in lung function 5, with differential expression observed in COPD patients. Additionally, TMC3 transcription is altered in spinocerebellar ataxia type 3 mouse models 6, and TMC3 expression serves as a prognostic indicator in papillary thyroid cancer 7. The related family member TMC4 negatively regulates KCNQ1 potassium channels 8, suggesting TMC proteins may function as channel regulators.

Sources cited
1
TMC3 is the most expressed channel of the TMC family in human cardiac fibroblasts and exhibits mechanosensitive ion channel activity
PMID: 38158807
2
TMC3 expression correlates with overall survival and immune infiltration in renal clear cell carcinoma
PMID: 37468683
3
TMC3-AS1 long non-coding RNA negatively regulates IL-10 expression through p65 interaction in immune cells
PMID: 32774335
4
TMC3-AS1 silencing alleviates acute kidney injury by suppressing Wnt5a-mediated autophagy and pyroptosis through miR-148a-3p regulation
PMID: 39732180
5
TMC3 locus associates with longitudinal decline in lung function and shows differential expression in COPD
PMID: 24983941
6
TMC3 transcription is significantly altered in spinocerebellar ataxia type 3 mouse brain
PMID: 29929540
7
TMC3 expression serves as a prognostic indicator for recurrence in papillary thyroid cancer
PMID: 34693452
8
TMC4 physically interacts with and negatively regulates KCNQ1 potassium channel function
PMID: 41046027
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.46Moderate
neurodegenerative diseaseOpen Targets
0.33Weak
pathological myopiaOpen Targets
0.26Weak
cholelithiasisOpen Targets
0.25Weak
placental retentionOpen Targets
0.25Weak
DermatochalasisOpen Targets
0.19Weak
measlesOpen Targets
0.19Weak
sialadenitisOpen Targets
0.19Weak
glaucomaOpen Targets
0.19Weak
Respiratory insufficiencyOpen Targets
0.18Weak
malunion fractureOpen Targets
0.17Weak
prostatitisOpen Targets
0.17Weak
tuberculosisOpen Targets
0.16Weak
placenta praeviaOpen Targets
0.08Suggestive
eyelid diseaseOpen Targets
0.03Suggestive
musculoskeletal system diseaseOpen Targets
0.03Suggestive
osteosarcomaOpen Targets
0.02Suggestive
acute kidney injuryOpen Targets
0.01Suggestive
parathyroid adenomaOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TMC5Shared pathway100%TMC7Shared pathway100%LASP1Shared pathway50%ANO7Shared pathway50%ANO2Shared pathway50%ANO8Shared pathway50%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
46%
Ovary
40%
Brain
31%
Lung
11%
Heart
2%
Gene Interaction Network
Click a node to explore
TMC3TMC5TMC7LASP1ANO7ANO2ANO8
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q7Z5M5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.03LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.86 [0.72–1.03]
RankingsWhere TMC3 stands among ~20K protein-coding genes
  • #16,594of 20,598
    Most Researched12
  • #10,252of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedTMC3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Transcriptomic profile of the mechanosensitive ion channelome in human cardiac fibroblasts.
PMID: 38158807
Exp Biol Med (Maywood) · 2023
1.00
2
Comprehensive analysis of the prognosis and immune infiltration of TMC family members in renal clear cell carcinoma.
PMID: 37468683
Sci Rep · 2023
0.90
3
LPS-Inducible lncRNA TMC3-AS1 Negatively Regulates the Expression of IL-10.
PMID: 32774335
Front Immunol · 2020
0.80
4
LncRNA TMC3-AS1 silence alleviates lipopolysaccharide-induced acute kidney injury by suppressing Wnt5a-mediated autophagy and pyroptosis pathway.
PMID: 39732180
Mol Cell Probes · 2025
0.70
5
Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.
PMID: 24983941
PLoS One · 2014
0.60