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6 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TM2D1
TM2 domain containing 1
Chromosome 1 · 1p31.3
NCBI Gene: 83941Ensembl: ENSG00000162604.14HGNC: HGNC:24142UniProt: Q9BX74
12PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingamyloid-beta bindingapoptotic signaling pathwayG protein-coupled receptor signaling pathwayneurodegenerative diseasebone remodeling diseasesecondary malignant neoplasmAbnormal pupillary function
✦AI Summary

TM2D1 (TM2 domain containing 1) is a protein implicated in amyloid-beta-induced apoptotic signaling. Based on functional studies, TM2D1 participates in apoptotic pathways potentially through interaction with amyloid-beta and related proteins 1. The protein contains conserved structural domains shared with related family members involved in G protein signaling modulation, though direct G protein coupling mechanisms remain unclear 2. In colorectal cancer models, TM2D1 functions as a key regulatory target of anesthetic agents. Sevoflurane and propofol co-treatment suppressed colorectal cancer cell proliferation, invasion, and migration while promoting apoptosis and ferroptosis—effects that were reversed by TM2D1 overexpression, establishing TM2D1 as a critical mediator of anesthetic-induced anti-tumor activity 3. Beyond oncology, TM2D1 was identified as one of six hub genes with high diagnostic significance for patients with co-occurring ankylosing spondylitis and sarcopenia, suggesting broader roles in inflammatory and metabolic disease pathways 4. Clinically, TM2D1 represents a potential therapeutic target for colorectal cancer treatment and may have diagnostic utility in musculoskeletal disease management. Its involvement in amyloid-beta signaling also suggests relevance to Alzheimer's disease pathophysiology, consistent with the broader disease associations of related TM2 domain proteins 5.

Sources cited
1
TM2D1 is a target of sevoflurane and propofol; TM2D1 overexpression reverses anesthetic-induced apoptosis and ferroptosis in colorectal cancer cells
PMID: 38920064
2
TM2D1 identified as one of six hub genes with high diagnostic significance for ankylosing spondylitis patients with sarcopenia
PMID: 41204493
3
Beta-amyloid peptide-binding protein family members contain G protein activation modules and regulate amyloid-beta-induced apoptosis
PMID: 11278849
4
Beta-amyloid peptide-binding protein structure and function in apoptotic signaling pathways
PMID: 12836168
5
TM2D3 (related TM2 domain protein) associated with Alzheimer's disease; suggests TM2 family involvement in amyloid-beta cascade
PMID: 27764101
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.30Weak
bone remodeling diseaseOpen Targets
0.29Weak
secondary malignant neoplasmOpen Targets
0.22Weak
Abnormal pupillary functionOpen Targets
0.21Weak
open-angle glaucomaOpen Targets
0.21Weak
connective tissue diseaseOpen Targets
0.19Weak
fracture of pelvisOpen Targets
0.13Weak
Abruptio PlacentaeOpen Targets
0.12Weak
multiple sclerosisOpen Targets
0.10Suggestive
heart failureOpen Targets
0.09Suggestive
placenta praeviaOpen Targets
0.09Suggestive
Blackfan-Diamond anemiaOpen Targets
0.08Suggestive
systolic heart failureOpen Targets
0.08Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.07Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.07Suggestive
inosine triphosphatase deficiencyOpen Targets
0.07Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.07Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.07Suggestive
Left bundle branch blockOpen Targets
0.06Suggestive
primary familial polycythemia due to EPO receptor mutationOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TM2D2Protein interaction98%DIDO1Shared pathway50%SLFN12Shared pathway50%DAPL1Shared pathway50%CASP8AP2Shared pathway33%DAP3Shared pathway33%
Tissue Expression6 tissues
Brain
100%
Heart
94%
Bone Marrow
85%
Ovary
84%
Lung
67%
Liver
53%
Gene Interaction Network
Click a node to explore
TM2D1TM2D2DIDO1SLFN12DAPL1CASP8AP2DAP3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9BX74
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.10LoF Tolerant
pLIⓘ
0.03Tolerant
Observed/Expected LoF0.58 [0.33–1.10]
RankingsWhere TM2D1 stands among ~20K protein-coding genes
  • #16,591of 20,598
    Most Researched12
  • #11,203of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedTM2D1
Sources retrieved6 papers
Response time—
📄 Sources
6▼
1
Sevoflurane and Propofol Co-affect the Development of Colorectal Cancer by Regulating TM2D1.
PMID: 38920064
Comb Chem High Throughput Screen · 2025
1.00
2
Identification of cross-diagnostic biomarkers in ankylosing spondylitis and sarcopenia by bioinformatics and machine learning.
PMID: 41204493
Medicine (Baltimore) · 2025
0.83
3
Cis- and trans-acting gene regulation is associated with osteoarthritis.
PMID: 16642435
Am J Hum Genet · 2006
0.67
4
Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.
PMID: 27764101
PLoS Genet · 2016
0.50
5
beta -Amyloid peptide-induced apoptosis regulated by a novel protein containing a g protein activation module.
PMID: 11278849
J Biol Chem · 2001
0.33