YY1

Chr 14AD

YY1 transcription factor

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

NCBI Gene: 7528 ENSG00000100811 UniProt: P25490 OMIM: 600013

YY1 encodes a zinc finger transcription factor that both activates and represses gene promoters by directing histone acetyltransferases and deacetylases to chromatin. Loss-of-function mutations cause Gabriele-de Vries syndrome through an autosomal dominant inheritance pattern. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

LOFmechanismADLOEUF 0.201 OMIM phenotype

Clinical Summary— YY1

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint

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

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

LoF OE0.00 (0.00–0.20)

0≤0.351.4

Missense OE0.40 (0.34–0.47)

0≤0.61.4

Synonymous OE1.20

0≤1.21.6

LoF obs/exp: 0 / 15.1Missense obs/exp: 97 / 241.8Syn Z: -1.55

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveYY1-related intellectual disabilityOTHERAD

0.3395th %ile

GOF

0.2298th %ile

LOF

0.87top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.20

Literature Evidence

LOFYY1 haploinsufficiency causes an intellectual disability syndrome featuring transcriptional and chromatin dysfunctionPMID:28575647

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.