HEY2
hes related family bHLH transcription factor with YRPW motif 2, the group of Basic helix-loop-helix proteins
Basic information
Region (hg38): 6:125747664-125761269
Links
Phenotypes
GenCC
Source:
- familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HEY2 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 | 2 | |||||
| missense | 33 | 34 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 0 | |||||
| Total | 0 | 0 | 34 | 2 | 1 |
Variants in HEY2
This is a list of pathogenic ClinVar variants found in the HEY2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-125749781-A-T | not specified | Uncertain significance (Feb 03, 2022) | ||
| 6-125749789-T-A | not specified | Uncertain significance (Apr 07, 2023) | ||
| 6-125749805-C-T | not specified | Uncertain significance (Dec 06, 2022) | ||
| 6-125749816-A-G | not specified | Uncertain significance (Aug 12, 2021) | ||
| 6-125749831-G-A | not specified | Uncertain significance (Mar 29, 2023) | ||
| 6-125749835-TG-T | Uncertain significance (Mar 10, 2022) | |||
| 6-125749858-G-C | not specified | Uncertain significance (Mar 15, 2024) | ||
| 6-125751808-A-G | not specified | Uncertain significance (Apr 06, 2024) | ||
| 6-125751814-T-C | not specified | Uncertain significance (Dec 22, 2023) | ||
| 6-125751994-T-C | not specified | Benign (-) | ||
| 6-125752015-G-C | Tetralogy of Fallot | Pathogenic (Apr 02, 2025) | ||
| 6-125752066-T-G | not specified | Benign (Dec 31, 2019) | ||
| 6-125752079-T-C | not specified | Uncertain significance (Sep 11, 2024) | ||
| 6-125752098-A-T | Benign (May 15, 2018) | |||
| 6-125754541-G-A | not specified | Uncertain significance (Sep 26, 2023) | ||
| 6-125754563-AT-A | not specified | Benign (-) | ||
| 6-125759237-G-C | not specified | Uncertain significance (Sep 20, 2024) | ||
| 6-125759242-C-T | not specified | Uncertain significance (Feb 22, 2025) | ||
| 6-125759254-C-T | not specified | Uncertain significance (Feb 26, 2025) | ||
| 6-125759268-C-G | not specified | Uncertain significance (Jan 29, 2024) | ||
| 6-125759288-C-T | not specified | Uncertain significance (Nov 15, 2024) | ||
| 6-125759297-C-T | not specified | Uncertain significance (Oct 08, 2024) | ||
| 6-125759302-T-C | not specified | Uncertain significance (Sep 17, 2021) | ||
| 6-125759324-C-T | not specified | Uncertain significance (Apr 22, 2022) | ||
| 6-125759335-C-T | not specified | Uncertain significance (Feb 13, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HEY2 | protein_coding | protein_coding | ENST00000368364 | 5 | 13606 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.893 | 0.106 | 125736 | 0 | 12 | 125748 | 0.0000477 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.854 | 182 | 217 | 0.837 | 0.0000135 | 2141 |
| Missense in Polyphen | 50 | 75.523 | 0.66205 | 716 | ||
| Synonymous | 0.307 | 91 | 94.8 | 0.960 | 0.00000710 | 722 |
| Loss of Function | 2.89 | 1 | 11.7 | 0.0858 | 6.64e-7 | 129 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000153 | 0.000152 |
| Ashkenazi Jewish | 0.000104 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000622 | 0.0000615 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000358 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Downstream effector of Notch signaling which may be required for cardiovascular development. Transcriptional repressor which binds preferentially to the canonical E box sequence 5'- CACGTG-3'. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6. {ECO:0000269|PubMed:10692439, ECO:0000269|PubMed:11095750, ECO:0000269|PubMed:15485867, ECO:0000269|PubMed:16293227}.;
- Pathway
- Breast cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Heart Development;Signaling by NOTCH1;Neural Crest Differentiation;Notch Signaling Pathway;RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Disease;Signal Transduction;Gene expression (Transcription);segmentation clock;Generic Transcription Pathway;RNA Polymerase II Transcription;p73 transcription factor network;Signaling by NOTCH1;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
- 0.180
Intolerance Scores
- loftool
- 0.383
- rvis_EVS
- -0.4
- rvis_percentile_EVS
- 26.53
Haploinsufficiency Scores
- pHI
- 0.372
- hipred
- Y
- hipred_score
- 0.875
- ghis
- 0.559
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.977
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hey2
- Phenotype
- homeostasis/metabolism 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); respiratory system phenotype; liver/biliary system phenotype;
Zebrafish Information Network
- Gene name
- hey2
- Affected structure
- pronephric glomerular capillary
- Phenotype tag
- abnormal
- Phenotype quality
- absent
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;blood vessel development;vasculogenesis;muscular septum morphogenesis;outflow tract morphogenesis;pulmonary valve morphogenesis;tricuspid valve morphogenesis;tricuspid valve formation;endocardial cushion to mesenchymal transition involved in heart valve formation;cardiac ventricle morphogenesis;cardiac left ventricle morphogenesis;cardiac right ventricle morphogenesis;ventricular trabecula myocardium morphogenesis;Notch signaling pathway;heart development;anterior/posterior axis specification;positive regulation of heart rate;negative regulation of transcription by transcription factor localization;negative regulation of gene expression;negative regulation of cardiac muscle cell apoptotic process;mesenchymal cell development;cardiac muscle hypertrophy in response to stress;cell differentiation;ascending aorta morphogenesis;dorsal aorta morphogenesis;umbilical cord morphogenesis;cell fate commitment;regulation of inner ear auditory receptor cell differentiation;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;smooth muscle cell differentiation;ventricular cardiac muscle cell development;positive regulation of cardiac muscle cell proliferation;cardiac epithelial to mesenchymal transition;heart trabecula formation;cardiac septum morphogenesis;ventricular septum morphogenesis;atrial septum morphogenesis;negative regulation of transcription initiation from RNA polymerase II promoter;labyrinthine layer blood vessel development;arterial endothelial cell differentiation;cardiac vascular smooth muscle cell development;coronary vasculature morphogenesis;pulmonary artery morphogenesis;Notch signaling involved in heart development;protein-DNA complex assembly;cochlea development;vascular smooth muscle cell development;negative regulation of transcription regulatory region DNA binding;negative regulation of cardiac vascular smooth muscle cell differentiation;negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation;regulation of vasculogenesis
- Cellular component
- nucleus;nucleoplasm;cytoplasm;Sin3 complex;transcriptional repressor complex
- Molecular function
- RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II activating transcription factor binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription corepressor activity;protein binding;transcription factor binding;microsatellite binding;protein homodimerization activity;histone deacetylase binding;sequence-specific DNA binding;protein heterodimerization activity;sequence-specific double-stranded DNA binding