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9 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TMEM68
transmembrane protein 68
Chromosome 8 · 8q12.1
NCBI Gene: 137695Ensembl: ENSG00000167904.16HGNC: HGNC:26510UniProt: E5RJN2
23PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
triglyceride biosynthetic processendoplasmic reticulum membranephospholipid:diacylglycerol acyltransferase activitymembraneneurodegenerative diseaseplacenta praeviaspondylolisthesisthyroid cancer
✦AI Summary

TMEM68 (transmembrane protein 68) is an endoplasmic reticulum-anchored acyltransferase that functions as a catalytic subunit of an alternative triacylglycerol (TAG) biosynthesis pathway 1. The protein synthesizes TAG from diacylglycerol and membrane phospholipids (particularly phosphatidylcholine and ether-linked phosphatidylcholine), thereby remodeling membrane lipid composition 1. TMEM68 exhibits both monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT) activities 2, operating independently of the canonical DGAT1/2 pathway 3. Mechanistically, TMEM68 is regulated by TMX1 at the endoplasmic reticulum, with loss of TMX1 leading to unconstrained lipid droplet formation 1. The pathway maintains mitochondrial function during extracellular lipid starvation and supports rapid growth when fuel sources are limiting 1. Beyond TAG synthesis, TMEM68 acts as a multifaceted regulator of membrane lipid homeostasis, reducing ether-linked glycerophospholipids and polyunsaturated fatty acids while increasing TAG and lipid droplet storage 3. Clinically, TMEM68 upregulation is associated with breast cancer proliferation and invasion, with higher expression correlating with poorer survival outcomes 4. TMEM68 was identified as a candidate modifier of breast cancer risk in genomic studies 5, and suggestive associations exist with dementia-related proteinopathy 6.

Sources cited
1
TMEM68 is a catalytic subunit of alternative TAG biosynthesis; synthesizes TAG from diacylglycerol and membrane phospholipids; maintained by TMX1 regulation; sustains mitochondrial function during lipid starvation
PMID: 37648867
2
TMEM68 promotes TAG synthesis independently of DGAT1/2; increases TAG at expense of membrane lipids; reduces ether-linked glycerophospholipids and polyunsaturated fatty acids
PMID: 39996489
3
TMEM68 exhibits MGAT and DGAT activities in conserved active site-dependent manner; increases TAG, diacylglycerol, and free fatty acid levels; affects glycerophospholipid composition
PMID: 36768334
4
TMEM68 is upregulated in breast cancer; higher expression associates with poorer survival; overexpression increases cell proliferation and invasion; regulates TAG metabolism and lipid droplet content
PMID: 39543690
5
TMEM68 identified as potential modifier of human breast cancer risk and outcome; falls within commonly amplified regions in breast cancer patients
PMID: 30914425
6
TMEM68 identified as suggestive proteinopathy-linked allele in dementia-related neuropathology with high biologic credibility
PMID: 38460116
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.42Moderate
placenta praeviaOpen Targets
0.31Weak
spondylolisthesisOpen Targets
0.23Weak
ovarian neoplasmOpen Targets
0.16Weak
thyroid cancerOpen Targets
0.16Weak
pathological myopiaOpen Targets
0.12Weak
frozen shoulderOpen Targets
0.11Weak
insomniaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
shortness of breathOpen Targets
0.07Suggestive
Abnormality of the skeletal systemOpen Targets
0.06Suggestive
cataractOpen Targets
0.06Suggestive
liver diseaseOpen Targets
0.06Suggestive
ocular hypotensionOpen Targets
0.06Suggestive
trauma complicationOpen Targets
0.06Suggestive
glycogen storage disease VIOpen Targets
0.04Suggestive
ankylosing spondylitisOpen Targets
0.02Suggestive
intracerebral hemorrhageOpen Targets
0.02Suggestive
nasopharyngeal carcinomaOpen Targets
0.01Suggestive
breast neoplasmOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
XKR4Protein interaction79%MOGAT1Shared pathway50%MOGAT3Shared pathway50%LPIN3Shared pathway33%AGMOShared pathway33%MOGAT2Shared pathway33%
Tissue Expression6 tissues
Brain
100%
Ovary
84%
Liver
80%
Heart
72%
Bone Marrow
72%
Lung
58%
Gene Interaction Network
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TMEM68XKR4MOGAT1MOGAT3LPIN3AGMOMOGAT2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q96MH6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.94LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.65 [0.46–0.94]
RankingsWhere TMEM68 stands among ~20K protein-coding genes
  • #13,550of 20,598
    Most Researched23
  • #8,773of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedTMEM68
Sources retrieved9 papers
Response time—
📄 Sources
9▼
1
Identification of an alternative triglyceride biosynthesis pathway.
PMID: 37648867
Nature · 2023
1.00
2
Human transmembrane protein 68 links triacylglycerol synthesis to membrane lipid homeostasis.
PMID: 39996489
FEBS J · 2025
0.89
3
Transmembrane Protein 68 Functions as an MGAT and DGAT Enzyme for Triacylglycerol Biosynthesis.
PMID: 36768334
Int J Mol Sci · 2023
0.78
4
The acyltransferase transmembrane protein 68 regulates breast cancer cell proliferation by modulating triacylglycerol metabolism.
PMID: 39543690
Lipids Health Dis · 2024
0.67
5
PLAG1 fusions define a third subtype of CNS embryonal tumor with PLAG family gene alteration.
PMID: 40751809
Acta Neuropathol · 2025
0.56