HES7
protein-codinghes family bHLH transcription factor 7, the group of Basic helix-loop-helix proteins
Gene summary
This gene encodes a member of the hairy and enhancer of split family of bHLH transcription factors. The mouse ortholog of this gene is regulated by Notch signaling. The protein functions as a transcriptional repressor, and is implicated in correct patterning of the axial skeleton. A mutation in this gene has been shown to result in spondylocostal dysostosis. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0010180
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013366
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0013366
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal; Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HES7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001165967.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 38 | 39 | |||
| missense | 3 | 2 | 69 | 1 | 75 | |
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 3 | 73 | 39 | 0 | 118 |
Highest pathogenic variant AF is 0.00003841478
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001159439.1 | 4 | MANE Select | |
| Ensembl | ENSP00000446205.2 | 4 | MANE Select | |
| RefSeq | NP_115969.2 | 4 | Standard | |
| Ensembl | ENSP00000314774.4 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| her5 | Danio rerio | Structure: pancreatic duct Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Human papillomavirus infection - Homo sapiens (human)
- Gene regulatory network modelling somitogenesis
- Mesodermal Commitment Pathway
- segmentation clock
Biological Process
- negative regulation of transcription by RNA polymerase II
- skeletal system development
- somitogenesis
- Notch signaling pathway
- mesoderm development
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- transcription corepressor activity
- transcription factor binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000541682
- Coding exons
- 4
- Length
- 3503
- Individuals with no LoFs
- 112771
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 112772
- p
- 0.00000443
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.760 | 79 | 100 | 0.787 | 0.00000456 | 1384 |
| Missense (PolyPhen) | 38 | 48.197 | 0.78844 | 665 | ||
| Synonymous | 1.67 | 31 | 45.3 | 0.685 | 0.00000213 | 516 |
| Loss of Function | 2.23 | 0 | 5.79 | 0.00 | 2.48e-7 | 81 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000059 | 0.000059 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional repressor. Represses transcription from both N box- and E box-containing promoters. May with HES1, cooperatively regulate somite formation in the presomitic mesoderm (PSM). May function as a segmentation clock, which is essential for coordinated somite segmentation (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Spondylocostal dysostosis 4, autosomal recessive (SCDO4) [MIM:613686]: A rare condition of variable severity characterized by vertebral and costal anomalies. The main feature include dwarfism, vertebral fusion, hemivertebrae, posterior rib fusion, reduced rib number, and other rib malformations. {ECO:0000269|PubMed:18775957, ECO:0000269|PubMed:20087400}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.114
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.822
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |