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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TMEM26
transmembrane protein 26
Chromosome 10 · 10q21.2
NCBI Gene: 219623Ensembl: ENSG00000196932.12HGNC: HGNC:28550UniProt: Q6ZUK4
18PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Swiss-Prot Reviewed
membraneneurodegenerative diseasepolycythemiabiliary tract diseaseAbnormality of the skeletal system
✦AI Summary

TMEM26 (transmembrane protein 26) is a plasma membrane-localized protein with context-dependent roles in cellular function and disease pathogenesis. As a beige adipose tissue marker 1, TMEM26 expression is elevated in fibro-fatty tissues associated with arrhythmogenic cardiomyopathy and correlates with thermogenic capacity in browning adipose tissue 23. TMEM26 is upregulated during white-to-brown adipose tissue transition in visceral adipose tissue proximal to colorectal tumors, suggesting involvement in metabolic remodeling 4. In epithelial tissues, TMEM26 functions as a pro-metastatic determinant in esophageal squamous cell carcinoma by disrupting tight junction protein assembly and activating NF-κB signaling to promote epithelial-mesenchymal transition 5. In breast cancer, TMEM26 exhibits dual, receptor-dependent functions: in estrogen receptor α (ERα)-positive tumors, it acts as a tumor suppressor by negatively regulating integrin β1 and reducing endocrine resistance risk 6. Conversely, high TMEM26 expression in ERα-negative/triple-negative breast cancer associates with increased recurrence risk, indicating oncogenic function in this context 6. Genetically, TMEM26 variants show interaction with excessive daytime sleepiness in sleep apnea pathogenesis 7, linking it to cardiometabolic complications. N-glycosylation regulates TMEM26 plasma membrane retention and functional expression 6.

Sources cited
1
TMEM26 is a beige fat marker with elevated expression in arrhythmogenic cardiomyopathy fibro-fatty tissues
PMID: 40223064
2
TMEM26 mRNA is increased in white adipose tissue undergoing browning in response to forskolin treatment
PMID: 40724856
3
TMEM26 is a browning-related molecule expressed in visceral adipose tissue from endometriosis patients
PMID: 39244839
4
TMEM26 marks white-brown adipose tissue transition in intra-tumoral visceral adipose tissue in colorectal cancer
PMID: 41053099
5
TMEM26 disrupts tight junctions and activates NF-κB signaling to promote epithelial-mesenchymal transition in esophageal squamous cell carcinoma
PMID: 37611445
6
TMEM26 acts as a tumor suppressor in ERα-positive breast cancer by negatively regulating integrin β1, but associates with poor prognosis in ERα-negative/triple-negative breast cancer
PMID: 27224909
7
TMEM26 exists as non-glycosylated and N-glycosylated isoforms; N-glycosylation is required for plasma membrane retention
PMID: 27224909
8
TMEM26 rare variants show interaction with excessive daytime sleepiness in sleep apnea susceptibility
PMID: 40736211
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.30Weak
polycythemiaOpen Targets
0.26Weak
biliary tract diseaseOpen Targets
0.25Weak
Abnormality of the skeletal systemOpen Targets
0.25Weak
diverticular diseaseOpen Targets
0.19Weak
polymyalgia rheumaticaOpen Targets
0.13Weak
immune system diseaseOpen Targets
0.13Weak
placental retentionOpen Targets
0.11Weak
cervical carcinomaOpen Targets
0.10Weak
intelligenceOpen Targets
0.09Suggestive
schizophreniaOpen Targets
0.09Suggestive
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
pancreatic adenocarcinomaOpen Targets
0.04Suggestive
type 1 diabetes mellitusOpen Targets
0.03Suggestive
facial nerve diseaseOpen Targets
0.03Suggestive
androgenetic alopeciaOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.02Suggestive
restless legs syndromeOpen Targets
0.02Suggestive
chronic kidney diseaseOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PPARGC1AProtein interaction94%CIDEAProtein interaction82%UCP1Protein interaction82%PRDM16Protein interaction82%TBX1Protein interaction79%TNFRSF9Protein interaction72%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
73%
Ovary
66%
Lung
52%
Heart
28%
Brain
12%
Gene Interaction Network
Click a node to explore
TMEM26PPARGC1ACIDEAUCP1PRDM16TBX1TNFRSF9
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6ZUK4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.68LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.22 [0.90–1.68]
RankingsWhere TMEM26 stands among ~20K protein-coding genes
  • #14,846of 20,598
    Most Researched18
  • #16,010of 17,882
    Most Constrained (LOEUF)1.68
Genes detectedTMEM26
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Small molecules for fat combustion: targeting obesity.
PMID: 30976490
Acta Pharm Sin B · 2019
1.00
2
Plasma CCL3 predicts adverse heart failure outcomes in patients with arrhythmogenic cardiomyopathy.
PMID: 40223064
BMC Med · 2025
0.90
3
The role of TMEM26 in disrupting tight junctions and activating NF-κB signaling to promote epithelial-mesenchymal transition in esophageal squamous cell carcinoma.
PMID: 37611445
Clinics (Sao Paulo) · 2023
0.80
4
Genome-wide gene by sleepiness interaction analysis for sleep apnea.
PMID: 40736211
Sleep · 2026
0.70
5
Evidence of Browning and Inflammation Features in Visceral Adipose Tissue of Women with Endometriosis.
PMID: 39244839
Arch Med Res · 2024
0.60