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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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TGIF1
TGFB induced factor homeobox 1
Chromosome 18 Β· 18p11.31
NCBI Gene: 7050Ensembl: ENSG00000177426.23HGNC: HGNC:11776UniProt: Q15583
119PubMed Papers
21Diseases
0Drugs
12Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
RNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription repressor activity, RNA polymerase II-specificprotein bindingsequence-specific double-stranded DNA bindingholoprosencephalyneurodegenerative diseaseholoprosencephaly 5microform holoprosencephaly
✦AI Summary

TGIF1 (TGFB-induced factor homeobox 1) is a transcriptional repressor that functions as a critical regulator of cell differentiation and developmental processes. As a DNA-binding homeobox protein, TGIF1 recognizes the consensus DNA motif 5'-TGTCA-3' through its TALE-type homeodomain and recruits corepressor complexes to modulate gene expression 1. TGIF1 acts as an active transcriptional corepressor of SMAD2 and mediates TGF-Ξ² pathway signaling 2, specifically participating in mitotic clonal expansion during adipogenesis through upregulation of C/EBPΞ² and inhibition of p27kip1 3. In reproductive tissues, TGIF1 inhibits granulosa cell viability while stimulating estradiol and progesterone production 4. Clinically, TGIF1 overexpression promotes glioma progression and predicts poor patient prognosis through pathways involving extracellular matrix and cell cycle regulation 5, and its expression is regulated by ERN1 endoribonuclease activity in glioblastoma cells 6. Genetic associations link TGIF1 polymorphisms to chr18 otitis media susceptibility 7, while mutations cause holoprosencephaly-4, reflecting TGIF1's role in forebrain development and ventral midline structure establishment. These findings position TGIF1 as a multifunctional transcriptional regulator with significant implications for developmental disorders and cancer progression.

Sources cited
1
TGIF1 homeodomain binds consensus DNA motif 5'-TGTCA-3' and undergoes conformational changes during DNA binding
PMID: 30048701
2
TGIF1 associates with SMAD3/4 and HDAC5 to form a corepressor complex that represses ANGPT2 in pericytes
PMID: 39129597
3
TGIF1 promotes mitotic clonal expansion during adipogenesis via C/EBPΞ² upregulation and p27kip1 inhibition
PMID: 38575107
4
TGIF1 inhibits granulosa cell proliferation and stimulates estradiol and progesterone production
PMID: 37660474
5
TGIF1 overexpression promotes glioma progression and predicts poor prognosis through cell cycle and extracellular matrix pathways
PMID: 35569122
6
TGIF1 expression in glioblastoma is regulated by ERN1 endoribonuclease activity
PMID: 38914217
7
TGIF1 polymorphisms associate with chronic otitis media susceptibility; TGIF1 involved in TGF-Ξ² signaling pathway
PMID: 28970529
8
TGIF1 C-terminal domain interacts with transcription factors including Smad2 and corepressor Sin3A
PMID: 31388821
Disease Associationsβ“˜21
holoprosencephalyOpen Targets
0.80Strong
neurodegenerative diseaseOpen Targets
0.53Moderate
holoprosencephaly 5Open Targets
0.38Weak
alobar holoprosencephalyOpen Targets
0.37Weak
lobar holoprosencephalyOpen Targets
0.37Weak
microform holoprosencephalyOpen Targets
0.37Weak
midline interhemispheric variant of holoprosencephalyOpen Targets
0.37Weak
semilobar holoprosencephalyOpen Targets
0.37Weak
septopreoptic holoprosencephalyOpen Targets
0.37Weak
colorectal adenocarcinomaOpen Targets
0.34Weak
HepatitisOpen Targets
0.32Weak
ovarian dysfunctionOpen Targets
0.25Weak
mixed connective tissue diseaseOpen Targets
0.24Weak
genetic disorderOpen Targets
0.19Weak
connective tissue diseaseOpen Targets
0.16Weak
vascular diseaseOpen Targets
0.11Weak
disorder of sexual differentiationOpen Targets
0.11Weak
Genetic 46,XY disorder of sex developmentOpen Targets
0.11Weak
Abnormality of the skeletal systemOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
Holoprosencephaly 4UniProt
Pathogenic Variants12
NM_003244.4(TGIF1):c.269G>A (p.Arg90His)Pathogenic
not provided|Holoprosencephaly 4
β˜…β˜…β˜†β˜†2024β†’ Residue 90
NM_003244.4(TGIF1):c.778del (p.Arg260fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 260
NM_003244.4(TGIF1):c.268C>T (p.Arg90Cys)Pathogenic
Holoprosencephaly 4
β˜…β˜†β˜†β˜†2025β†’ Residue 90
NM_003244.4(TGIF1):c.177C>A (p.Tyr59Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 59
NM_003244.4(TGIF1):c.319C>T (p.Gln107Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 107
NM_003244.4(TGIF1):c.257del (p.Phe86fs)Pathogenic
Holoprosencephaly 4
β˜…β˜†β˜†β˜†2023β†’ Residue 86
NM_003244.4(TGIF1):c.214del (p.Ser72fs)Likely pathogenic
Holoprosencephaly 4
β˜…β˜†β˜†β˜†2023β†’ Residue 72
NC_000018.10:g.(?_3447720)_(3457960_?)delPathogenic
Holoprosencephaly 4
β˜…β˜†β˜†β˜†2018
NM_003244.4(TGIF1):c.708dup (p.Pro237fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 237
NM_003244.4(TGIF1):c.16+1651C>GPathogenic
Holoprosencephaly 4
β˜†β˜†β˜†β˜†2003
NM_003244.4(TGIF1):c.188C>G (p.Pro63Arg)Pathogenic
Holoprosencephaly 4
β˜†β˜†β˜†β˜†2000β†’ Residue 63
NM_003244.4(TGIF1):c.16+1805delLikely pathogenic
Holoprosencephaly 4
β˜†β˜†β˜†β˜†
View on ClinVar β†—
Related Genes
SMAD4Protein interaction100%SMAD2Protein interaction99%SMAD3Protein interaction99%TGIF2Protein interaction93%CTBP1Protein interaction88%CTBP2Protein interaction88%
Tissue Expression6 tissues
Lung
100%
Liver
91%
Ovary
85%
Bone Marrow
64%
Brain
30%
Heart
25%
Gene Interaction Network
Click a node to explore
TGIF1SMAD4SMAD2SMAD3TGIF2CTBP1CTBP2
PROTEIN STRUCTURE
Preparing viewer…
PDB6FQP Β· 2.42 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.48Moderately Constrained
pLIβ“˜
0.98Intolerant
Observed/Expected LoF0.21 [0.10–0.48]
RankingsWhere TGIF1 stands among ~20K protein-coding genes
  • #3,978of 20,598
    Most Researched119 Β· top quartile
  • #2,662of 5,498
    Most Pathogenic Variants12
  • #2,771of 17,882
    Most Constrained (LOEUF)0.48 Β· top quartile
Genes detectedTGIF1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301702
1.00
2
Molecular characterization and effects of the TGIF1 gene on proliferation and steroidogenesis in yak (Bos grunniens) granulosa cells.
PMID: 37660474
Theriogenology Β· 2023
0.90
3
Inhibition of ERN1 affects the expression of TGIF1 and other homeobox gene expressions in U87MG glioblastoma cells.
PMID: 38914217
Arch Biochem Biophys Β· 2024
0.80
4
Backbone and side chain resonance assignments of the C-terminal domain of human TGIF1.
PMID: 31388821
Biomol NMR Assign Β· 2019
0.70
5
Characterization of the interaction interface and conformational dynamics of human TGIF1 homeodomain upon the binding of consensus DNA.
PMID: 30048701
Biochim Biophys Acta Proteins Proteom Β· 2018
0.60