HES7

hes family bHLH transcription factor 7, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 17:8120592-8124106

Links

ENSG00000179111 ∙ NCBI:84667 ∙ OMIM:608059 ∙ HGNC:15977 ∙ Uniprot:Q9BYE0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondylocostal dysostosis 4, autosomal recessive (Strong), mode of inheritance: AR
• autosomal recessive spondylocostal dysostosis (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondylocostal dysostosis 4, autosomal recessive	AR	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	Musculoskeletal; Neurologic	18775957; 20087400; 20301771

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HES7 gene.

• 30 conditions (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HES7 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				25	3	28
missense		1	49			50
nonsense						0
start loss						0
frameshift		1				1
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			4	1		5
non coding			2	7	4	13
Total	0	2	53	32	7

Variants in HES7

This is a list of pathogenic ClinVar variants found in the HES7 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-8121440-C-A			Benign (Jun 19, 2021)
17-8121490-C-A			Benign (Jun 20, 2021)
17-8121559-A-C			Uncertain significance (Aug 17, 2017)
17-8121582-G-A			Uncertain significance (Oct 13, 2022)
17-8121582-G-C			Uncertain significance (Mar 03, 2022)
17-8121583-T-A			Uncertain significance (Dec 03, 2022)
17-8121625-C-T			Likely benign (Jun 22, 2023)
17-8121627-C-G			Uncertain significance (Jun 20, 2021)
17-8121643-C-T			Likely benign (Jun 13, 2022)
17-8121646-C-T			Likely benign (Nov 08, 2022)
17-8121649-T-C			Likely benign (Sep 21, 2022)
17-8121650-G-A			Uncertain significance (Aug 22, 2022)
17-8121656-G-GGCA			Uncertain significance (Jun 14, 2021)
17-8121659-A-G			Uncertain significance (Mar 17, 2022)
17-8121668-G-A		Inborn genetic diseases	Uncertain significance (Apr 18, 2024)
17-8121673-G-A		HES7-related disorder	Conflicting classifications of pathogenicity (Jan 26, 2024)
17-8121681-G-C			Uncertain significance (Feb 25, 2022)
17-8121685-G-T			Likely benign (May 22, 2023)
17-8121686-C-T		Inborn genetic diseases	Uncertain significance (Apr 08, 2024)
17-8121687-C-T		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
17-8121693-C-A		Spondylocostal dysostosis 4, autosomal recessive	Pathogenic (Jun 01, 2010)
17-8121698-G-A			Uncertain significance (Aug 23, 2022)
17-8121703-C-G			Likely benign (Oct 04, 2022)
17-8121707-G-T			Uncertain significance (Nov 15, 2022)
17-8121713-A-G			Uncertain significance (May 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HES7	protein_coding	protein_coding	ENST00000541682	4	3503

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.827	0.170	112771	0	1	112772	0.00000443

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.760	79	100	0.787	0.00000456	1384
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000589	0.0000589
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000589	0.0000589
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: Human papillomavirus infection - Homo sapiens (human);Gene regulatory network modelling somitogenesis;Mesodermal Commitment Pathway;segmentation clock (Consensus)

Recessive Scores

• pRec: 0.114

Haploinsufficiency Scores

• pHI: 0.274
• hipred: N
• hipred_score: 0.417
• ghis: 0.618

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.822

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hes7
• 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); embryo phenotype; skeleton phenotype; limbs/digits/tail phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: her5
• Affected structure: pancreatic duct
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;skeletal system development;somitogenesis;Notch signaling pathway;mesoderm development;regulation of somitogenesis;cell differentiation;post-anal tail morphogenesis;rhythmic process;regulation of neurogenesis
• Cellular component: nucleus
• 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;sequence-specific DNA binding;protein dimerization activity;sequence-specific double-stranded DNA binding