HEY1 (hes related family bHLH transcription factor with YRPW motif 1)

Gene

• Entrez ID: 23462
• Gene name: Hes related family bHLH transcription factor with YRPW motif 1
• Gene symbol: HEY1
• Synonyms (NCBI Gene): BHLHb31, CHF2, HERP2, HESR1, HRT-1, NERP2, OAF1, hHRT1
• Chromosome: 8
• Chromosome location: 8q21.13
• Summary: This gene encodes a nuclear protein belonging to the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcriptional repressors. Expression of this gene is induced by the Notch and c-Jun signal transduction pathways

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017049	hsa-miR-335-5p	Microarray	18185580
MIRT019763	hsa-miR-375	Microarray	20215506
MIRT046126	hsa-miR-30b-5p	CLASH	23622248
MIRT1044795	hsa-miR-1207-3p	CLIP-seq
MIRT1044796	hsa-miR-132	CLIP-seq
MIRT1044797	hsa-miR-182	CLIP-seq
MIRT1044798	hsa-miR-212	CLIP-seq
MIRT1044799	hsa-miR-455-3p	CLIP-seq
MIRT1044800	hsa-miR-4690-3p	CLIP-seq
MIRT1044801	hsa-miR-4709-5p	CLIP-seq
MIRT1044802	hsa-miR-4781-3p	CLIP-seq
MIRT1044803	hsa-miR-548c-3p	CLIP-seq
MIRT1044804	hsa-miR-599	CLIP-seq
MIRT2009768	hsa-miR-1178	CLIP-seq
MIRT1044795	hsa-miR-1207-3p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
DUX4	Activation	24278031
JUN	Activation	15314183
MAML1	Repression	18503747
MSX1	Activation	18201699
NR2F2	Unknown	23345397

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	16043483, 18239137, 21290414
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IMP	11486045
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	ISS
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IDA	21290414
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0000987	Function	Cis-regulatory region sequence-specific DNA binding	IDA	18239137
GO:0001227	Function	DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA	18239137
GO:0001227	Function	DNA-binding transcription repressor activity, RNA polymerase II-specific	ISS
GO:0001525	Process	Angiogenesis	IEP	11866539
GO:0003161	Process	Cardiac conduction system development	NAS	26786210
GO:0003180	Process	Aortic valve morphogenesis	ISS
GO:0003184	Process	Pulmonary valve morphogenesis	ISS
GO:0003190	Process	Atrioventricular valve formation	ISS
GO:0003203	Process	Endocardial cushion morphogenesis	ISS
GO:0003208	Process	Cardiac ventricle morphogenesis	ISS
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IDA	15485867
GO:0005515	Function	Protein binding	IPI	15485867, 21454491, 32296183, 33961781, 34819669
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	ISS
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	ISS
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0007219	Process	Notch signaling pathway	IBA
GO:0007219	Process	Notch signaling pathway	IDA	10964718, 25985737
GO:0007219	Process	Notch signaling pathway	IEA
GO:0007219	Process	Notch signaling pathway	ISS
GO:0009653	Process	Anatomical structure morphogenesis	IEA
GO:0009952	Process	Anterior/posterior pattern specification	IBA
GO:0035912	Process	Dorsal aorta morphogenesis	ISS
GO:0036304	Process	Umbilical cord morphogenesis	ISS
GO:0045665	Process	Negative regulation of neuron differentiation	IBA
GO:0045746	Process	Negative regulation of Notch signaling pathway	IDA	18239137
GO:0045892	Process	Negative regulation of DNA-templated transcription	IDA	15485867
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0046983	Function	Protein dimerization activity	IEA
GO:0050767	Process	Regulation of neurogenesis	IBA
GO:0051151	Process	Negative regulation of smooth muscle cell differentiation	IDA	18239137
GO:0060317	Process	Cardiac epithelial to mesenchymal transition	ISS
GO:0060347	Process	Heart trabecula formation	ISS
GO:0060411	Process	Cardiac septum morphogenesis	ISS
GO:0060412	Process	Ventricular septum morphogenesis	ISS
GO:0060716	Process	Labyrinthine layer blood vessel development	ISS
GO:0060842	Process	Arterial endothelial cell differentiation	ISS
GO:0061629	Function	RNA polymerase II-specific DNA-binding transcription factor binding	IPI	10692439
GO:0070168	Process	Negative regulation of biomineral tissue development	ISS
GO:0072359	Process	Circulatory system development	IBA
GO:0072359	Process	Circulatory system development	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536
GO:2001212	Process	Regulation of vasculogenesis	ISS

Other IDs

• MIM: 602953
• HGNC: 4880
• e!Ensembl: ENSG00000164683

Protein

• UniProt ID: Q9Y5J3
• Protein name: Hairy/enhancer-of-split related with YRPW motif protein 1 (Cardiovascular helix-loop-helix factor 2) (CHF-2) (Class B basic helix-loop-helix protein 31) (bHLHb31) (HES-related repressor protein 1) (Hairy and enhancer of split-related protein 1) (HESR-1) (
• Protein function: Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3' (PubMed:11095750). Downstream effector of Notch signaling required for cardiovascular development. Specifically required for the Notch-induced endo
• PDB: 2DB7
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00010	HLH	50 → 105	Helix-loop-helix DNA-binding domain	Domain
  PF07527	Hairy_orange	121 → 163	Hairy Orange	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in the somitic mesoderm, the central nervous system, the kidney, the heart, nasal epithelium, and limbs.
• Sequence:

  MKRAHPEYSSSDSELDETIEVEKESADENGNLSSALGSMSPTTSSQILARKRRRGIIEKR
  RRDRINNSLSELRRLVPSAFEKQGSAKLEKAEILQMTVDHLKMLHTAGGKGYFDAHALAM
  DYRSLGFRECLAEVARYLSIIEGLDASDPLRVRLVSHLNNYASQREAASGAHAGLGHIPW
  GTVFGHHPHIAHPLLLPQNGHGNAGTTASPTEPHHQGRLGSAHPEAPALRAPPSGSLGPV
  LPVVTSASKLSPPLLSSVASLSAFPFSFGSFHLLSPNALSPSAPTQAANLGKPYRPWGTE
  IGAF

• Sequence length: 304

Pathways

KEGG:

Notch signaling pathway
Human papillomavirus infection
Pathways in cancer
Breast cancer

Reactome:

Constitutive Signaling by NOTCH1 PEST Domain Mutants
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
NOTCH4 Intracellular Domain Regulates Transcription

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ASTROCYTOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, PANCREATIC DUCTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART DISEASE	—	ClinGen, Disgenet ClinGen, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOBLASTOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEY1-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
URETERAL OBSTRUCTION	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Aortic Arch Syndromes	Associate	34549899	★☆☆☆☆ Found in Text Mining only
Brain Neoplasms	Associate	24487962	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Associate	20010940	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinogenesis	Associate	34837064	★☆☆☆☆ Found in Text Mining only
Carcinoma Adenoid Cystic	Associate	32025208	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Stimulate	27420998	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Associate	40507937	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Associate	27766950, 32432737	★☆☆☆☆ Found in Text Mining only
Chondrosarcoma Mesenchymal	Associate	22034177, 23185413, 24839999, 30819134, 34837064, 35342947, 35672279, 37225644, 40301759	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Associate	23900217, 30565566	★☆☆☆☆ Found in Text Mining only
Death	Stimulate	23900217	★☆☆☆☆ Found in Text Mining only
Epidermolysis bullosa with pyloric atresia	Associate	25575134	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Associate	25361534	★☆☆☆☆ Found in Text Mining only
Fractures Bone	Associate	35401881	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Associate	23787764, 28574840, 30195713	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Glioma	Associate	24487962, 30195713	★☆☆☆☆ Found in Text Mining only
Head and Neck Neoplasms	Associate	35672279	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Associate	34549899	★☆☆☆☆ Found in Text Mining only
Hemangioma capillary infantile	Associate	37565874	★☆☆☆☆ Found in Text Mining only
Hypoxia	Stimulate	20010940, 22275240	★☆☆☆☆ Found in Text Mining only
Hypoxia	Inhibit	22172337	★☆☆☆☆ Found in Text Mining only
Hypoxia	Associate	25166211, 25734817	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Associate	34768865	★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Stimulate	23900217	★☆☆☆☆ Found in Text Mining only
Mouth Diseases	Associate	24839999	★☆☆☆☆ Found in Text Mining only
Neoplasm Metastasis	Stimulate	32025208	★☆☆☆☆ Found in Text Mining only
Neoplasm Metastasis	Associate	34837064	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	23226563, 24839999, 24931473, 32025208, 37967237	★☆☆☆☆ Found in Text Mining only
Neoplasms	Stimulate	23900217, 24487962	★☆☆☆☆ Found in Text Mining only
Neuroendocrine Tumors	Associate	22918166	★☆☆☆☆ Found in Text Mining only
Obesity	Associate	35401881	★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Associate	37796700	★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Associate	23226563	★☆☆☆☆ Found in Text Mining only
Precursor T Cell Lymphoblastic Leukemia Lymphoma	Associate	19835636	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Associate	21454491	★☆☆☆☆ Found in Text Mining only
Rhabdomyosarcoma Alveolar	Inhibit	23733015	★☆☆☆☆ Found in Text Mining only
Rhabdomyosarcoma Embryonal	Associate	23733015	★☆☆☆☆ Found in Text Mining only
Sarcoma	Associate	22337624, 29104083	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Associate	24351288, 29146722	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Associate	33236952, 34925644	★☆☆☆☆ Found in Text Mining only