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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

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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ClinVar Variants

47 unique Pathogenic / Likely Pathogenic· 81 VUS of 160 total submissions

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Clinical Trials

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

Explore recent and relevant literature in Research Assistant →

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GeneReview available — YY1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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 OE?0.00 (0.00–0.20)

0≤0.351.4

Missense OE?0.40 (0.34–0.47)

0≤0.61.4

Synonymous OE?1.20

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

This gene — mechanism propensity

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 · 38% of P/LP variants are LoF · LOEUF 0.20

Literature Evidence

LOFYY1 haploinsufficiency causes an intellectual disability syndrome featuring transcriptional and chromatin dysfunction1

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

References

1.PMID 28575647 ↗

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic27

VUS81

Likely Benign21

Benign2

Conflicting4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	8	0	0	20
Likely Pathogenic	6	20	0	1	27
VUS	1	78	1	1	81
Likely Benign	0	3	4	14	21
Benign	0	2	0	0	2
Conflicting	—				4
Total	19	111	5	16	155

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

View in ClinVar →

36 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap YY1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →