HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TMBIM4
transmembrane BAX inhibitor motif containing 4
Chromosome 12 · 12q14.3
NCBI Gene: 51643Ensembl: ENSG00000155957.19HGNC: HGNC:24257UniProt: G3V1M2
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of calcium-mediated signalingendoplasmic reticulum membraneGolgi stackprotein bindingmixed connective tissue diseaseAbnormal pupillary functionhemorrhoidprostate carcinoma
✦AI Summary

TMBIM4 (transmembrane BAX inhibitor motif containing 4), also known as GAAP (Golgi anti-apoptotic protein), is a ubiquitously expressed 1, multi-transmembrane cation-selective ion channel 2 with primary functions in apoptosis inhibition and calcium homeostasis. TMBIM4 localizes to both the Golgi apparatus and endoplasmic reticulum 1, and more recently to the plasma membrane 3. It regulates intracellular Ca2+ fluxes through store-operated entry and IP3-mediated release 2, reduces endoplasmic reticulum Ca2+ content 1, and confers resistance to diverse apoptotic stimuli 2. Functionally, TMBIM4 enhances cell migration and invasion through focal adhesion turnover 4 and promotes hydrogen peroxide accumulation affecting cell invasiveness 4. Developmentally, TMBIM4 controls left-right patterning during gastrulation by regulating pluripotency exit through membrane potential maintenance 3. Disease relevance includes congenital heart disease with cardiac heterotaxy from TMBIM4 variants 3, preeclampsia where TMBIM4 deficiency facilitates NLRP3 inflammasome-induced trophoblast pyroptosis 5, age-related cataracts where miR-125a-3p suppression of TMBIM4 increases lens epithelial cell apoptosis 6, and hypertension susceptibility in African-ancestry populations 7. These findings establish TMBIM4 as a multifunctional protein critical for cellular survival, developmental patterning, and disease prevention.

Sources cited
1
TMBIM4 (transmembrane BAX inhibitor motif containing 4), also known as GAAP (Golgi anti-apoptotic protein), is a ubiquitously expressed , multi-transmembrane cation-selective ion channel with primary functions in apoptosis inhibition and calcium homeostasis.
PMID: 25764978
2
TMBIM4 (transmembrane BAX inhibitor motif containing 4), also known as GAAP (Golgi anti-apoptotic protein), is a ubiquitously expressed , multi-transmembrane cation-selective ion channel with primary functions in apoptosis inhibition and calcium homeostasis.
PMID: 28469007
3
TMBIM4 localizes to both the Golgi apparatus and endoplasmic reticulum , and more recently to the plasma membrane .
PMID: 40744297
4
Functionally, TMBIM4 enhances cell migration and invasion through focal adhesion turnover and promotes hydrogen peroxide accumulation affecting cell invasiveness .
PMID: 31693977
5
Disease relevance includes congenital heart disease with cardiac heterotaxy from TMBIM4 variants , preeclampsia where TMBIM4 deficiency facilitates NLRP3 inflammasome-induced trophoblast pyroptosis , age-related cataracts where miR-125a-3p suppression of TMBIM4 increases lens epithelial cell apoptosis , and hypertension susceptibility in African-ancestry populations .
PMID: 36829486
6
Disease relevance includes congenital heart disease with cardiac heterotaxy from TMBIM4 variants , preeclampsia where TMBIM4 deficiency facilitates NLRP3 inflammasome-induced trophoblast pyroptosis , age-related cataracts where miR-125a-3p suppression of TMBIM4 increases lens epithelial cell apoptosis , and hypertension susceptibility in African-ancestry populations .
PMID: 36173547
7
Disease relevance includes congenital heart disease with cardiac heterotaxy from TMBIM4 variants , preeclampsia where TMBIM4 deficiency facilitates NLRP3 inflammasome-induced trophoblast pyroptosis , age-related cataracts where miR-125a-3p suppression of TMBIM4 increases lens epithelial cell apoptosis , and hypertension susceptibility in African-ancestry populations .
PMID: 28498854
Disease Associationsⓘ20
Abnormal pupillary functionOpen Targets
0.19Weak
mixed connective tissue diseaseOpen Targets
0.19Weak
hemorrhoidOpen Targets
0.08Suggestive
prostate carcinomaOpen Targets
0.06Suggestive
thyroiditisOpen Targets
0.05Suggestive
hepatocellular carcinomaOpen Targets
0.05Suggestive
complicationOpen Targets
0.05Suggestive
trauma complicationOpen Targets
0.05Suggestive
Venous thrombosisOpen Targets
0.05Suggestive
abscessOpen Targets
0.05Suggestive
Rectal abscessOpen Targets
0.05Suggestive
aortic stenosisOpen Targets
0.04Suggestive
aortic valve calcificationOpen Targets
0.04Suggestive
WheezingOpen Targets
0.04Suggestive
amyotrophic lateral sclerosisOpen Targets
0.04Suggestive
medical procedureOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
age-related macular degenerationOpen Targets
0.03Suggestive
Ischemic strokeOpen Targets
0.03Suggestive
Behcet's syndromeOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ITPR3Protein interaction93%PMLProtein interaction90%EIF4EProtein interaction85%SIGMAR1Protein interaction83%TMEM97Protein interaction83%IFIH1Protein interaction75%
Tissue Expression6 tissues
Liver
100%
Lung
83%
Brain
71%
Ovary
70%
Heart
35%
Bone Marrow
32%
Gene Interaction Network
Click a node to explore
TMBIM4ITPR3PMLEIF4ESIGMAR1TMEM97IFIH1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q7Z782
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.77LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.08 [0.65–1.77]
RankingsWhere TMBIM4 stands among ~20K protein-coding genes
  • #13,776of 20,598
    Most Researched22
  • #16,410of 17,882
    Most Constrained (LOEUF)1.77
Genes detectedTMBIM4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
TMBIM4 affects left-right patterning via pluripotency exit during gastrulation.
PMID: 40744297
Dev Biol · 2025
1.00
2
TMBIM4 Deficiency Facilitates NLRP3 Inflammasome Activation-Induced Pyroptosis of Trophoblasts: A Potential Pathogenesis of Preeclampsia.
PMID: 36829486
Biology (Basel) · 2023
0.90
3
Golgi anti-apoptotic protein: a tale of camels, calcium, channels and cancer.
PMID: 28469007
Open Biol · 2017
0.80
4
miR-125a-3p regulates apoptosis by suppressing TMBIM4 in lens epithelial cells.
PMID: 36173547
Int Ophthalmol · 2023
0.70
5
Stimulation of cell invasion by the Golgi Ion Channel GAAP/TMBIM4 via an H
PMID: 31693977
Redox Biol · 2020
0.60