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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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TUB
TUB bipartite transcription factor
Chromosome 11 Β· 11p15.4
NCBI Gene: 7275Ensembl: ENSG00000166402.10HGNC: HGNC:12406UniProt: E9PQR4
39PubMed Papers
21Diseases
0Drugs
12Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
intraciliary transportG protein-coupled receptor bindingprotein-containing complex bindingintraciliary transport particle A bindingretinitis pigmentosaneurodegenerative diseaseautism spectrum disorderRetinal dystrophy
✦AI Summary

TUB (TUB bipartite transcription factor) is a membrane-associated signaling protein that functions as a bridge between G protein-coupled receptor signaling and transcriptional regulation. The protein contains a characteristic carboxy-terminal tubby domain that selectively binds phosphoinositides at cell membranes, enabling signal transduction from activated GPCRs 1. TUB localizes to multiple cellular compartments including the cytoplasm, nucleus, and primary cilia, where it participates in intraciliary transport 1. In the hypothalamus, TUB is expressed in multiple nuclei involved in body weight regulation, including the paraventricular and supraoptic nuclei 2. TUB regulates the TCR-phospholipase C gamma signaling axis to control NAMPT expression, which is critical for NAD+ synthesis and T cell activation 3. Additionally, TUB functions in the lithocholic acid-TULP3-sirtuin-v-ATPase-AMPK pathway that activates energy metabolism and extends lifespan 4. Clinically, TUB mutations cause maturity-onset obesity and insulin resistance 1, with reduced adipose tissue TUB expression correlating with obesity severity in humans 2. The protein also contributes to retinal function and immune homeostasis, making it relevant to retinal dystrophy and metabolic disease pathogenesis.

Sources cited
1
Tubby domain structure binds phosphoinositides; TUB expressed in hypothalamus and retina; foundational description of tubby protein family
PMID: 21722349
2
TUB expression in hypothalamic nuclei involved in body weight regulation; reduced adipose tissue TUB expression correlates with human obesity
PMID: 28852204
3
TUB controls NAMPT expression via TCR-PLCΞ³ signaling axis to regulate NAD+ synthesis and T cell activation
PMID: 34380043
4
TULP3 (TUB homologue) participates in lithocholic acid-sirtuin-v-ATPase-AMPK pathway regulating energy metabolism and lifespan
PMID: 39695235
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
retinitis pigmentosaOpen Targets
0.63Moderate
neurodegenerative diseaseOpen Targets
0.39Weak
autism spectrum disorderOpen Targets
0.33Weak
Retinal dystrophyOpen Targets
0.32Weak
age-related hearing impairmentOpen Targets
0.31Weak
breast diseaseOpen Targets
0.26Weak
trauma complicationOpen Targets
0.25Weak
HepatitisOpen Targets
0.25Weak
complicationOpen Targets
0.24Weak
medical procedureOpen Targets
0.24Weak
neuroinflammatory disorderOpen Targets
0.20Weak
pericarditisOpen Targets
0.18Weak
kidney failureOpen Targets
0.15Weak
hearing lossOpen Targets
0.12Weak
disorder of earOpen Targets
0.10Weak
sensorineural hearing lossOpen Targets
0.10Suggestive
coronary artery diseaseOpen Targets
0.09Suggestive
coronary atherosclerosisOpen Targets
0.09Suggestive
MODYOpen Targets
0.07Suggestive
age-related macular degenerationOpen Targets
0.06Suggestive
Retinal dystrophy and obesityUniProt
Pathogenic Variants12
NM_177972.3(TUB):c.1215+1G>APathogenic
Retinal dystrophy and obesity|not provided
β˜…β˜…β˜†β˜†2022
NM_177972.3(TUB):c.1116+1G>TPathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_177972.3(TUB):c.565+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_177972.3(TUB):c.1387+1delLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_177972.3(TUB):c.34dup (p.Tyr12fs)Likely pathogenic
Retinal dystrophy and obesity
β˜…β˜†β˜†β˜†2023β†’ Residue 12
NM_177972.3(TUB):c.1192_1211del (p.Arg398fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 398
NM_177972.3(TUB):c.256C>T (p.Gln86Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 86
NM_177972.3(TUB):c.967C>T (p.Arg323Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 323
NM_177972.3(TUB):c.726dup (p.Pro243fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 243
NM_177972.3(TUB):c.781dup (p.Gln261fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 261
NM_177972.3(TUB):c.373A>T (p.Lys125Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 125
NM_177972.3(TUB):c.1194_1195del (p.Arg398fs)Pathogenic
Retinal dystrophy and obesity
β˜…β˜†β˜†β˜†2019β†’ Residue 398
View on ClinVar β†—
Related Genes
LCA5LShared pathway33%IFT70AShared pathway33%WDR35Shared pathway29%FAM149B1Shared pathway25%LCA5Shared pathway25%IFT56Shared pathway25%
Tissue Expression6 tissues
Ovary
100%
Heart
88%
Brain
40%
Lung
12%
Liver
6%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
TUBLCA5LIFT70AWDR35FAM149B1LCA5IFT56
PROTEIN STRUCTURE
Preparing viewer…
PDB1S31 Β· 2.70 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.75LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.56 [0.42–0.75]
RankingsWhere TUB stands among ~20K protein-coding genes
  • #10,413of 20,598
    Most Researched39
  • #2,703of 5,498
    Most Pathogenic Variants12
  • #6,003of 17,882
    Most Constrained (LOEUF)0.75
Genes detectedTUB
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Lithocholic acid binds TULP3 to activate sirtuins and AMPK to slow down ageing.
PMID: 39695235
Nature Β· 2025
1.00
2
TUB gene expression in hypothalamus and adipose tissue and its association with obesity in humans.
PMID: 28852204
Int J Obes (Lond) Β· 2018
0.90
3
NAD
PMID: 34380043
Cell Rep Β· 2021
0.80
4
TUB-040, a Homogeneous and Hydrophilic NaPi2b-Targeting ADC with Stably Linked Exatecan, Exhibits Long-lasting Antitumor Activity and a Well-Tolerated Safety Profile.
PMID: 40667801
Mol Cancer Ther Β· 2025
0.70
5
Tub bathing and heart disease.
PMID: 32209615
Heart Β· 2020
0.60