HSF2

protein-coding

heat shock transcription factor 2

Gene summary

The protein encoded by this gene belongs to the HSF family of transcription factors that bind specifically to the heat-shock promoter element and activate transcription. Heat shock transcription factors activate heat-shock response genes under conditions of heat or other stresses. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

MANE transcript

NM_004506.4

Inheritance

—

ClinVar variants

U:48

Top phenotype

Variant of unknown significance

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr6:122,399,551-122,433,119

External References & Databases

Ensembl (ENSG00000025156)

Transcript & Mutation Effects

hg38 • Region Span ~33.6 kb

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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 HSF2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 2

Variant of unknown significanceTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004506.4. 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						0
missense			47 clinvar			47
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	48	0	0	48

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004506.4	RefSeq	NP_004497.1	13	MANE Select
ENST00000368455.9	Ensembl	ENSP00000357440.4	13	MANE Select
NM_001135564.1	RefSeq	NP_001129036.1	12	Standard
NM_001243094.2	RefSeq	NP_001230023.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Validated nuclear estrogen receptor alpha network

Biological Process

transcription by RNA polymerase II
spermatogenesis
cellular response to heat
positive regulation of transcription by RNA polymerase II
positive regulation of transcription from RNA polymerase II promoter in response to heat stress

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific

Cellular Component

nucleus
nucleoplasm
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368455
Coding exons: 13
Length: 33574
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125739
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.07	179	276	0.649	0.0000131	3578
Missense (PolyPhen)		41	94.323	0.43468		1346
Synonymous	-0.763	109	99.3	1.10	0.00000476	968
Loss of Function	4.30	4	29.0	0.138	0.00000149	351

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	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000068	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: DNA-binding protein that specifically binds heat shock promoter elements (HSE) and activates transcription. In higher eukaryotes, HSF is unable to bind to the HSE unless the cells are heat shocked.;

Recessive Scores

pRec: 0.174

Intolerance Scores

LoFtool: 0.115
RVIS EVS: -0.76
RVIS percentile EVS: 13.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.881

Gene Damage Prediction

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