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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TMEM119
transmembrane protein 119
Chromosome 12 · 12q23.3
NCBI Gene: 338773Ensembl: ENSG00000183160.10HGNC: HGNC:27884UniProt: Q4V9L6
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of osteoblast differentiationpositive regulation of bone mineralizationpositive regulation of osteoblast proliferationplasma membraneglaucomaosteoarthritis, kneeopen-angle glaucomamedical procedure
✦AI Summary

TMEM119 (transmembrane protein 119) is a transmembrane protein with dual roles in bone metabolism and neuroinflammation. In bone biology, TMEM119 promotes myoblast differentiation into osteoblasts and enhances bone mineralization, likely through BMP2 production and the BMP-RUNX2 pathway, with upregulation of the transcription factor ATF4 1. TMEM119 upregulation contributes to osteoblast bone formation and may counteract oxidative stress-induced osteoporosis 1. In the central nervous system, TMEM119 functions as a microglial homeostatic marker. Microglial TMEM119 binds amyloid-β oligomers and promotes their clearance through low-density lipoprotein receptor 1-mediated degradation 2. In Alzheimer's disease, TMEM119 expression decreases in microglia, and TMEM119 deficiency accelerates disease progression in mouse models 2. Pharmacological enhancement of TMEM119 expression with small molecules improved amyloid clearance and cognitive function even at mid-disease stages 2. However, TMEM119 is not exclusively microglial; it is also expressed by follicular dendritic cells and brown adipose tissue, and expression significantly decreases under cellular stress conditions 3. In Alzheimer's disease brains, TMEM119+-microglia prevalence substantially decreased compared to controls 4. These findings position TMEM119 as a promising therapeutic target for Alzheimer's disease, though interpretation as a pan-microglial marker requires caution.

Sources cited
1
Microglial TMEM119 binds amyloid-β, promotes clearance through LDL receptor 1, and TMEM119 overexpression enhances microglial phagocytosis and alleviates cognitive deficits in AD mice
PMID: 40373772
2
Tmem119 upregulation by Nrf2 activation promotes osteoblastic bone formation and rescues estrogen-deficiency-induced osteoporosis
PMID: 36592659
3
In Alzheimer's disease patients, significant loss of TMEM119+-microglia phenotypes occurs independent of β-amyloid plaque proximity
PMID: 35247551
4
TMEM119 is not exclusively expressed by microglia, is expressed by follicular dendritic cells and brown adipose tissue, and expression decreases under cellular stress conditions
PMID: 35246882
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
glaucomaOpen Targets
0.47Moderate
osteoarthritis, kneeOpen Targets
0.44Moderate
open-angle glaucomaOpen Targets
0.42Moderate
medical procedureOpen Targets
0.34Weak
response to xenobiotic stimulusOpen Targets
0.34Weak
neoplasmOpen Targets
0.10Weak
gastric cancerOpen Targets
0.09Suggestive
Alzheimer diseaseOpen Targets
0.09Suggestive
osteosarcomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
hyperpituitarismOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
gastric adenocarcinomaOpen Targets
0.07Suggestive
strokeOpen Targets
0.06Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.06Suggestive
azoospermiaOpen Targets
0.06Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.06Suggestive
46,XY disorder of sex development due to 5-alpha-reductase 2 deficiencyOpen Targets
0.05Suggestive
46,XX ovotesticular disorder of sex developmentOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CST7Protein interaction87%OLFML3Protein interaction87%SALL1Protein interaction75%C1QAProtein interaction74%CX3CR1Protein interaction74%TREM2Protein interaction74%
Tissue Expression6 tissues
Lung
100%
Heart
45%
Bone Marrow
12%
Brain
11%
Ovary
3%
Liver
2%
Gene Interaction Network
Click a node to explore
TMEM119CST7OLFML3SALL1C1QACX3CR1TREM2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q4V9L6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.82LoF Tolerant
pLIⓘ
0.35Tolerant
Observed/Expected LoF0.00 [0.00–1.82]
RankingsWhere TMEM119 stands among ~20K protein-coding genes
  • #14,039of 20,598
    Most Researched21
  • #16,680of 17,882
    Most Constrained (LOEUF)1.82
Genes detectedTMEM119
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Microglial TMEM119 binds to amyloid-β to promote its clearance in an Aβ-depositing mouse model of Alzheimer's disease.
PMID: 40373772
Immunity · 2025
1.00
2
Beyond Activation: Characterizing Microglial Functional Phenotypes.
PMID: 34571885
Cells · 2021
0.90
3
Co-expression patterns of microglia markers Iba1, TMEM119 and P2RY12 in Alzheimer's disease.
PMID: 35247551
Neurobiol Dis · 2022
0.80
4
A Combination of Ontogeny and CNS Environment Establishes Microglial Identity.
PMID: 29861285
Neuron · 2018
0.70
5
Transmembrane protein 119 is neither a specific nor a reliable marker for microglia.
PMID: 35246882
Glia · 2022
0.60