HES5

protein-coding

hes family bHLH transcription factor 5, the group of Basic helix-loop-helix proteins

Gene summary

This gene encodes a member of a family of basic helix-loop-helix transcriptional repressors. The protein product of this gene, which is activated downstream of the Notch pathway, regulates cell differentiation in multiple tissues. Disruptions in the normal expression of this gene have been associated with developmental diseases and cancer. [provided by RefSeq, Dec 2008]

MANE transcript

NM_001010926.4

Inheritance

—

ClinVar variants

U:30B:2

Top phenotype

HES5-related condition

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr1:2,528,745-2,530,263

External References & Databases

Ensembl (ENSG00000197921)

Transcript & Mutation Effects

hg38 • Region Span ~1.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HES5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 29

not providedTotal: 2

HES5-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001010926.4. 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 clinvar	1 clinvar	2
missense			30 clinvar			30
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	30	1	1	32

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001010926.4	RefSeq	NP_001010926.1	3	MANE Select
ENST00000378453.4	Ensembl	ENSP00000367714.3	3	MANE Select
ENST00001144301.1	Ensembl	ENSP00000810892.1	3	Standard
XM_005244751.5	RefSeq	XP_005244808.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
her2	Danio rerio	Structure: trunk Quality: bent abnormal

Gene / Model

Organism

Observed Phenotype

her2

Danio rerio

Structure: trunk

Quality: bent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Breast cancer - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)
Notch signaling pathway - Homo sapiens (human)
Human papillomavirus infection - Homo sapiens (human)
Signaling by NOTCH2

Biological Process

negative regulation of transcription by RNA polymerase II
somitogenesis
chondrocyte differentiation
cell adhesion
Notch signaling pathway

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
chromatin binding
transcription corepressor activity

Cellular Component

cellular_component
nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378453
Coding exons: 3
Length: 1501
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.594	49	38.6	1.27	0.00000174	1038
Missense (PolyPhen)		25	21.329	1.1721		356
Synonymous	-0.549	19	16.2	1.17	7.44e-7	327
Loss of Function	1.20	1	3.39	0.295	1.47e-7	60

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	0.0	absent
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: dbNSFP

Function: FUNCTION: Transcriptional repressor of genes that require a bHLH protein for their transcription. Plays an important role as neurogenesis negative regulator (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.423

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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