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50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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YY1
YY1 transcription factor
Chromosome 14 Β· 14q32.2
NCBI Gene: 7528Ensembl: ENSG00000100811.15HGNC: HGNC:12856UniProt: P25490
557PubMed Papers
21Diseases
0Drugs
46Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairHighly ConstrainedHomologous RecombinationHub GeneTranscription Factor
RESEARCH IMPACT
Highly Studied
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
negative regulation of transcription by RNA polymerase IIRNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription factor activity, RNA polymerase II-specificcis-regulatory region sequence-specific DNA bindingGabriele de Vries syndromeIntellectual disabilitygenetic disordercomplex neurodevelopmental disorder
✦AI Summary

YY1 (Yin Yang 1) is a multifunctional transcription factor that serves as a structural regulator of chr14 architecture and gene expression. YY1's primary function involves forming enhancer-promoter loops through homodimer formation, analogous to CTCF-mediated interactions, where it binds to active enhancers and promoter-proximal elements to facilitate long-range DNA interactions essential for mammalian gene control 1. Mechanistically, YY1 operates through multiple pathways: it can function as both a transcriptional activator and repressor depending on context, with its C-terminal domain (residues 296-414) responsible for transcriptional activation 2. YY1 also undergoes liquid-liquid phase separation when complexed with HDAC1/3, which modulates its transcriptional activity and target gene expression 3. The protein's stability is regulated by the ubiquitin-proteasome system, with OTUD3 serving as a key deubiquitinase that prevents YY1 degradation 4. YY1 has significant disease relevance, particularly in cancer where it promotes tumor progression by cooperating with other factors to drive oncogene expression 5 and modulating drug sensitivity 6. Additionally, YY1 plays a critical role in extrachromosomal DNA biogenesis through DNA looping and religation mechanisms 7. Clinically, YY1 expression levels correlate with patient prognosis in various cancers, making it a potential therapeutic target.

Sources cited
1
YY1 forms dimers to facilitate enhancer-promoter looping and is essential for mammalian gene control
PMID: 29224777
2
YY1's C-terminal domain (residues 296-414) is responsible for transcriptional activation
PMID: 31818358
3
YY1 undergoes liquid-liquid phase separation when complexed with HDAC1/3 to regulate gene expression
PMID: 36424383
4
OTUD3 serves as a deubiquitinase that regulates YY1 stability
PMID: 38351178
5
YY1 cooperates with other factors to promote tumor progression by driving oncogene expression
PMID: 37928273
6
YY1 modulates drug sensitivity in cancer through the HDAC2 complex
PMID: 35974388
7
YY1 plays a critical role in extrachromosomal DNA biogenesis through DNA looping and religation mechanisms
PMID: 40769147
Disease Associationsβ“˜21
Gabriele de Vries syndromeOpen Targets
0.79Strong
Intellectual disabilityOpen Targets
0.61Moderate
genetic disorderOpen Targets
0.45Moderate
complex neurodevelopmental disorderOpen Targets
0.37Weak
intellectual disability, autosomal dominant 40Open Targets
0.37Weak
Neurodevelopmental disorderOpen Targets
0.30Weak
neurodegenerative diseaseOpen Targets
0.28Weak
genetic developmental and epileptic encephalopathyOpen Targets
0.27Weak
external ear diseaseOpen Targets
0.17Weak
neoplasmOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
colorectal carcinomaOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
cancerOpen Targets
0.11Weak
gastric cancerOpen Targets
0.11Weak
posterior cortical atrophyOpen Targets
0.11Weak
rheumatoid arthritisOpen Targets
0.11Weak
glioblastoma multiformeOpen Targets
0.11Weak
acute myeloid leukemiaOpen Targets
0.10Weak
melanomaOpen Targets
0.10Weak
Gabriele-de Vries syndromeUniProt
Pathogenic Variants46
NM_003403.5(YY1):c.1124G>A (p.Arg375Gln)Pathogenic
not provided|Gabriele de Vries syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 375
NM_003403.5(YY1):c.690dup (p.Asp231fs)Pathogenic
not provided|Gabriele de Vries syndrome|Intellectual disability
β˜…β˜…β˜†β˜†2025β†’ Residue 231
NM_003403.5(YY1):c.1106A>G (p.Asn369Ser)Pathogenic
Gabriele de Vries syndrome|Intellectual disability|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 369
NM_003403.5(YY1):c.1057T>C (p.Phe353Leu)Likely pathogenic
Gabriele de Vries syndrome
β˜…β˜…β˜†β˜†2023β†’ Residue 353
NM_003403.5(YY1):c.1112G>A (p.Arg371His)Likely pathogenic
Gabriele de Vries syndrome
β˜…β˜…β˜†β˜†2021β†’ Residue 371
NM_003403.5(YY1):c.468_483del (p.Gly157fs)Pathogenic
Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2020β†’ Residue 157
NM_003403.5(YY1):c.1043C>T (p.Thr348Ile)Likely pathogenic
Gabriele de Vries syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 348
NM_003403.5(YY1):c.264del (p.Leu89fs)Likely pathogenic
Gabriele de Vries syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 89
NM_003403.5(YY1):c.1175A>C (p.Lys392Thr)Likely pathogenic
Gabriele de Vries syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 392
NM_003403.5(YY1):c.1124G>T (p.Arg375Leu)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 375
NM_003403.5(YY1):c.842+1G>CLikely pathogenic
Gabriele de Vries syndrome
β˜…β˜†β˜†β˜†2024
NM_003403.5(YY1):c.1133C>G (p.Thr378Ser)Likely pathogenic
Developmental and epileptic encephalopathy, 78
β˜…β˜†β˜†β˜†2024β†’ Residue 378
NM_003403.5(YY1):c.1062+1G>TLikely pathogenic
Gabriele de Vries syndrome
β˜…β˜†β˜†β˜†2024
NM_003403.5(YY1):c.1024C>T (p.Arg342Ter)Pathogenic
Gabriele de Vries syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 342
NM_003403.5(YY1):c.1148A>G (p.Tyr383Cys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 383
NM_003403.5(YY1):c.1147_1151dup (p.Cys385fs)Pathogenic
Gabriele de Vries syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 385
NM_003403.5(YY1):c.1123C>T (p.Arg375Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 375
NM_003403.5(YY1):c.943A>G (p.Lys315Glu)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 315
NM_003403.5(YY1):c.1192A>G (p.Thr398Ala)Likely pathogenic
Gabriele de Vries syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 398
NM_003403.5(YY1):c.980G>A (p.Cys327Tyr)Pathogenic
Gabriele de Vries syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 327
View on ClinVar β†—
Related Genes
PPARGC1AProtein interaction100%TP53Protein interaction100%ACTR5Protein interaction100%RYBPProtein interaction100%NCOR1Protein interaction100%MBTD1Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
79%
Heart
52%
Liver
51%
Lung
49%
Ovary
40%
Gene Interaction Network
Click a node to explore
YY1PPARGC1ATP53ACTR5RYBPNCOR1MBTD1
PROTEIN STRUCTURE
Preparing viewer…
PDB1UBD Β· 2.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.20Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.06 [0.03–0.20]
RankingsWhere YY1 stands among ~20K protein-coding genes
  • #439of 20,598
    Most Researched557 Β· top 5%
  • #1,396of 5,498
    Most Pathogenic Variants46
  • #449of 17,882
    Most Constrained (LOEUF)0.20 Β· top 5%
Genes detectedYY1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
YY1 Is a Structural Regulator of Enhancer-Promoter Loops.
PMID: 29224777
Cell Β· 2017
1.00
2
CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1.
PMID: 37928273
Int J Biol Sci Β· 2023
0.90
3
Multifunctional YY1 in Liver Diseases.
PMID: 29272897
Semin Liver Dis Β· 2017
0.86
4
YTHDC1 is downregulated by the YY1/HDAC2 complex and controls the sensitivity of ccRCC to sunitinib by targeting the ANXA1-MAPK pathway.
PMID: 35974388
J Exp Clin Cancer Res Β· 2022
0.80
5
YY1 interacts with guanine quadruplexes to regulate DNA looping and gene expression.
PMID: 33199912
Nat Chem Biol Β· 2021
0.80