YY1

YY1 transcription factor, the group of INO80 complex |Zinc fingers C2H2-type

Basic information

Region (hg38): 14:100238297-100282788

Links

ENSG00000100811 ∙ NCBI:7528 ∙ OMIM:600013 ∙ HGNC:12856 ∙ Uniprot:P25490 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
• Gabriele de Vries syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Gabriele-de Vries syndrome (GADEVS)	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	28575647

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the YY1 gene.

• not provided (34 variants)
• Gabriele de Vries syndrome (24 variants)
• Inborn genetic diseases (13 variants)
• YY1-related condition (2 variants)
• Neurodevelopmental disorder (2 variants)
• Intellectual disability (1 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YY1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	5		6
missense	3	14	26	1	2	46
nonsense						0
start loss						0
frameshift	3	2				5
inframe indel			4	2		6
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding			1	1		2
Total	7	16	32	9	2

Variants in YY1

This is a list of pathogenic ClinVar variants found in the YY1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-100239240-C-T		Gabriele de Vries syndrome	Uncertain significance (Mar 05, 2019)
14-100239253-G-A		YY1-related disorder	Likely benign (Dec 01, 2023)
14-100239258-A-C		Inborn genetic diseases	Uncertain significance (Feb 22, 2021)
14-100239274-C-T			Likely benign (Dec 18, 2018)
14-100239275-A-T			Uncertain significance (Mar 14, 2023)
14-100239317-G-A			Uncertain significance (Apr 27, 2022)
14-100239385-G-C			Benign (Dec 31, 2019)
14-100239385-GGACGAC-G			Uncertain significance (Nov 01, 2023)
14-100239388-C-G		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
14-100239401-GACGGCGGCGGTGGCGACC-G		Gabriele de Vries syndrome	Conflicting classifications of pathogenicity (May 01, 2023)
14-100239406-CGGCGGT-C			Uncertain significance (Mar 01, 2023)
14-100239410-G-A		Gabriele de Vries syndrome	Uncertain significance (Dec 15, 2021)
14-100239419-CACGGCG-C			Likely benign (Oct 01, 2022)
14-100239432-G-A		Gabriele de Vries syndrome	Uncertain significance (Feb 10, 2021)
14-100239437-C-T		Inborn genetic diseases	Uncertain significance (Aug 08, 2023)
14-100239438-A-G		Gabriele de Vries syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 01, 2023)
14-100239443-C-G		Inborn genetic diseases	Uncertain significance (Oct 03, 2023)
14-100239445-C-T		YY1-related disorder	Likely benign (Feb 01, 2024)
14-100239446-G-A		Gabriele de Vries syndrome	Uncertain significance (Sep 13, 2019)
14-100239450-GCCACCA-G		Inborn genetic diseases	Likely benign (Dec 09, 2021)
14-100239450-GCCACCACCACCACCACCATCA-G		not specified	Uncertain significance (Sep 18, 2023)
14-100239450-G-GCCA		Gabriele de Vries syndrome	Conflicting classifications of pathogenicity (Aug 01, 2023)
14-100239453-A-C		Inborn genetic diseases	Uncertain significance (Dec 18, 2023)
14-100239469-T-C			Likely benign (Mar 01, 2023)
14-100239488-C-T		Inborn genetic diseases	Uncertain significance (Nov 30, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YY1	protein_coding	protein_coding	ENST00000262238	5	44495

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00620	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.31	97	242	0.401	0.0000119	2707
Missense in Polyphen		6	59.651	0.10059		696
Synonymous	-1.55	121	101	1.20	0.00000548	797
Loss of Function	3.60	0	15.1	0.00	8.24e-7	187

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes by binding to sites overlapping the transcription start site. Binds to the consensus sequence 5'-CCGCCATNTT-3'; some genes have been shown to contain a longer binding motif allowing enhanced binding; the initial CG dinucleotide can be methylated greatly reducing the binding affinity. The effect on transcription regulation is depending upon the context in which it binds and diverse mechanisms of action include direct activation or repression, indirect activation or repression via cofactor recruitment, or activation or repression by disruption of binding sites or conformational DNA changes. Its activity is regulated by transcription factors and cytoplasmic proteins that have been shown to abrogate or completely inhibit YY1-mediated activation or repression. For example, it acts as a repressor in absence of adenovirus E1A protein but as an activator in its presence. Acts synergistically with the SMAD1 and SMAD4 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression (PubMed:15329343). Binds to SMAD binding elements (SBEs) (5'- GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions. May play an important role in development and differentiation. Proposed to recruit the PRC2/EED-EZH2 complex to target genes that are transcriptional repressed. Involved in DNA repair. In vitro, binds to DNA recombination intermediate structures (Holliday junctions). Plays a role in regulating enhancer activation (PubMed:28575647). {ECO:0000269|PubMed:15329343, ECO:0000269|PubMed:24326773, ECO:0000269|PubMed:25787250, ECO:0000269|PubMed:28575647}.
• Disease: DISEASE: Gabriele-de Vries syndrome (GADEVS) [MIM:617557]: An autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development and intellectual disability. Most patients have behavioral and feeding problems, movement abnormalities, mild distal skeletal anomalies, and dysmorphic facial features. {ECO:0000269|PubMed:21076407, ECO:0000269|PubMed:28575647}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Notch;DNA Repair;Signal Transduction;Gene expression (Transcription);the prc2 complex sets long-term gene silencing through modification of histone tails;Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;UCH proteinases;Deubiquitination;Signaling by Nuclear Receptors;Notch signaling pathway;TFAP2 (AP-2) family regulates transcription of growth factors and their receptors;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Estrogen-dependent gene expression;DNA Damage Recognition in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);ESR-mediated signaling;Notch-mediated HES/HEY network;mTOR signaling pathway;Signaling events mediated by HDAC Class I;E2F transcription factor network;p53 pathway;Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.546

Intolerance Scores

• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.11

Haploinsufficiency Scores

• pHI: 0.889
• hipred: Y
• hipred_score: 0.794
• ghis: 0.496

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Yy1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; skeleton phenotype; embryo phenotype; respiratory system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: yy1a
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: increased branchiness

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;double-strand break repair via homologous recombination;regulation of transcription by RNA polymerase II;RNA localization;cellular response to DNA damage stimulus;spermatogenesis;anterior/posterior pattern specification;response to UV-C;negative regulation of gene expression;protein deubiquitination;cell differentiation;negative regulation of interferon-beta production;cellular response to UV;response to prostaglandin F;positive regulation of transcription by RNA polymerase II;camera-type eye morphogenesis;chromosome organization;cellular response to interleukin-1;negative regulation of pri-miRNA transcription by RNA polymerase II
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;transcription factor complex;cytoplasm;nuclear matrix;Ino80 complex;PcG protein complex
• Molecular function: four-way junction DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;proximal promoter sequence-specific DNA binding;enhancer sequence-specific DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;transcription corepressor activity;RNA binding;protein binding;zinc ion binding;histone deacetylase binding;sequence-specific DNA binding;transcription regulatory region DNA binding;SMAD binding