YY1

Chr 14AD

YY1 transcription factor

Also known as: DELTA, GADEVS, INO80S, NF-E1, UCRBP, YIN-YANG-1

NCBI Gene: 7528ENSG00000100811UniProt: P25490

YY1 is a ubiquitously distributed transcription factor belonging to the GLI-Kruppel class of zinc finger proteins. The protein is involved in repressing and activating a diverse number of promoters. YY1 may direct histone deacetylases and histone acetyltransferases to a promoter in order to activate or repress the promoter, thus implicating histone modification in the function of YY1. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Gabriele-de Vries syndromeMIM #617557
AD
192
ClinVar variants
82
Pathogenic / LP
0.99
pLI score· haploinsufficient
1
Active trials
Clinical Summary— YY1
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
82 Pathogenic / Likely Pathogenic· 84 VUS of 192 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.20LOEUF
pLI 0.994
Z-score 3.60
OE 0.00 (0.00–0.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.31Z-score
OE missense 0.40 (0.34–0.47)
97 obs / 241.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.40 (0.34–0.47)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.20
0≤1.21.6
LoF obs/exp: 0 / 15.1Missense obs/exp: 97 / 241.8Syn Z: -1.55

ClinVar Variant Classifications

192 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic28
VUS84
Likely Benign20
Benign2
Conflicting4
54
Pathogenic
28
Likely Pathogenic
84
VUS
20
Likely Benign
2
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
8
38
0
54
Likely Pathogenic
5
20
2
1
28
VUS
0
65
18
1
84
Likely Benign
0
1
6
13
20
Benign
0
2
0
0
2
Conflicting
—4
Total13966415192

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

YY1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

YY1-related intellectual disability

definitive
ADUndeterminedUncertain
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Gabriele-de Vries syndrome

MIM #617557

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — YY1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6.
Chen S et al.·J Immunother Cancer
2023
PRMT1 driven PTX3 regulates ferritinophagy in glioma.
Lathoria K et al.·Autophagy
2023
METTL16 promotes glycolytic metabolism reprogramming and colorectal cancer progression.
Wei W et al.·J Exp Clin Cancer Res
2023
YY1 enhances HIF-1α stability in tumor-associated macrophages to suppress anti-tumor immunity of prostate cancer in mice.
Li W et al.·Nat Commun
2025
LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway.
He Y et al.·Mol Cancer
2021
Identification and validation of CCR5 linking keloid with atopic dermatitis through comprehensive bioinformatics analysis and machine learning.
Zhou B et al.·Front Immunol
2024
MAGEA6 Engages a YY1-Dependent Transcription to Dictate Perineural Invasion in Colorectal Cancer.
Wang H et al.·Adv Sci (Weinh)
2025
Extrachromosomal DNA biogenesis is dependent on DNA looping and religation by YY1-Lig3-PARylation complex.
Qin LN et al.·Mol Cell
2025
Hippo pathway activation mediates cardiomyocyte ferroptosis to promote dilated cardiomyopathy through downregulating NFS1.
She G et al.·Redox Biol
2025
CD24 is a promising immunotherapeutic target for enhancing efficacy of third-generation EGFR-TKIs on EGFR-mutated lung cancer.
Liang J et al.·Cancer Commun (Lond)
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools