HEY1

hes related family bHLH transcription factor with YRPW motif 1, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 8:79762371-79767857

Links

ENSG00000164683 ∙ NCBI:23462 ∙ OMIM:602953 ∙ HGNC:4880 ∙ Uniprot:Q9Y5J3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HEY1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HEY1 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				6	1	7
missense			16	1	1	18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					7	7
Total	0	0	16	7	9

Variants in HEY1

This is a list of pathogenic ClinVar variants found in the HEY1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-79765029-T-A			Benign (Nov 12, 2018)
8-79765215-A-G		HEY1-related disorder	Likely benign (Apr 29, 2020)
8-79765249-G-A		HEY1-related disorder	Likely benign (Mar 01, 2019)
8-79765292-A-G		HEY1-related disorder	Benign (Apr 08, 2019)
8-79765337-A-G		not specified	Uncertain significance (Apr 20, 2024)
8-79765348-G-A		not specified	Uncertain significance (Apr 17, 2024)
8-79765367-A-T		not specified	Uncertain significance (Mar 02, 2023)
8-79765387-G-A		not specified	Uncertain significance (Oct 05, 2021)
8-79765388-G-A		not specified	Uncertain significance (Feb 28, 2024)
8-79765427-C-A		not specified	Uncertain significance (Jan 10, 2023)
8-79765472-T-C		not specified	Uncertain significance (Feb 13, 2023)
8-79765525-G-A		not specified	Uncertain significance (Mar 11, 2024)
8-79765544-G-A		not specified	Uncertain significance (Jul 26, 2021)
8-79765553-A-G		not specified	Uncertain significance (Sep 08, 2024)
8-79765577-C-T		not specified	Uncertain significance (Dec 06, 2021)
8-79765681-A-G		not specified	Uncertain significance (Dec 15, 2022)
8-79765707-T-G		HEY1-related disorder	Likely benign (Oct 28, 2019)
8-79765719-C-T		HEY1-related disorder	Likely benign (Mar 21, 2019)
8-79765728-C-T		HEY1-related disorder	Likely benign (Nov 01, 2022)
8-79765754-C-A		not specified	Uncertain significance (Feb 22, 2023)
8-79765763-C-T		not specified	Uncertain significance (Sep 15, 2021)
8-79765887-G-A			Benign (Jun 19, 2021)
8-79766065-C-CA			Benign (Nov 12, 2018)
8-79766192-T-C			Benign (Nov 12, 2018)
8-79766258-AGGCATGT-A		HEY1-related disorder	Benign (Jun 19, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HEY1	protein_coding	protein_coding	ENST00000337919	5	3854

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0502	0.930	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.504	160	179	0.894	0.00000807	1936
Missense in Polyphen		43	69.719	0.61676		814
Synonymous	-0.837	91	81.4	1.12	0.00000389	676
Loss of Function	2.03	4	11.4	0.351	5.12e-7	130

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000920	0.0000912
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.0000269	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000661	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 endocardial epithelial to mesenchymal transition, which is itself criticial for cardiac valve and septum development. May be required in conjunction with HEY2 to specify arterial cell fate or identity. Promotes maintenance of neuronal precursor cells and glial versus neuronal fate specification. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6 and by the neuronal bHLH factors ASCL1/MASH1 and NEUROD4/MATH3 (PubMed:15485867). Involved in the regulation of liver cancer cells self-renewal (PubMed:25985737). {ECO:0000250|UniProtKB:Q9WV93, ECO:0000269|PubMed:11095750, ECO:0000269|PubMed:15485867, ECO:0000269|PubMed:25985737}.
• Pathway: Breast cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Heart Development;Signaling by NOTCH1;miR-148a-miR-31-FIH1-HIF1α-Notch signaling in glioblastoma;Canonical and Non-canonical Notch signaling;Notch Signaling Pathway;RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Disease;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Signaling by NOTCH1;NOTCH3 Intracellular Domain Regulates Transcription;Signaling by NOTCH3;Signaling by NOTCH;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Notch-mediated HES/HEY network;Diseases of signal transduction;NOTCH1 Intracellular Domain Regulates Transcription (Consensus)

Recessive Scores

• pRec: 0.234

Intolerance Scores

• loftool: 0.426
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.35

Haploinsufficiency Scores

• pHI: 0.486
• hipred: Y
• hipred_score: 0.827
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.441

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hey1
• Phenotype: cellular phenotype; craniofacial phenotype; muscle phenotype; growth/size/body region phenotype; embryo 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); normal phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;angiogenesis;blood vessel development;pulmonary valve morphogenesis;atrioventricular valve formation;endocardial cushion morphogenesis;cardiac ventricle morphogenesis;Notch signaling pathway;heart development;cell differentiation;dorsal aorta morphogenesis;umbilical cord morphogenesis;negative regulation of Notch signaling pathway;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of neurogenesis;cardiac epithelial to mesenchymal transition;heart trabecula formation;cardiac septum morphogenesis;ventricular septum morphogenesis;labyrinthine layer blood vessel development;arterial endothelial cell differentiation;Notch signaling involved in heart development;negative regulation of transcription regulatory region DNA binding;negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation;regulation of vasculogenesis
• Cellular component: nucleus;nucleoplasm;cytoplasm
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription corepressor activity;protein binding;transcription factor binding;microsatellite binding;sequence-specific DNA binding;protein dimerization activity;sequence-specific double-stranded DNA binding