HSF5

protein-coding

heat shock transcription factor 5

Gene summary

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including male meiotic nuclear division; regulation of DNA-templated transcription; and spermatogenesis. Predicted to be located in XY body. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001080439.3

Inheritance

—

ClinVar variants

U:50B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr17:58,420,167-58,488,408

External References & Databases

Ensembl (ENSG00000176160)

Transcript & Mutation Effects

hg38 • Region Span ~68.2 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 HSF5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 51

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080439.3. 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
missense			50 clinvar	3 clinvar		53
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	4	0	54

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080439.3	RefSeq	NP_001073908.2	6	MANE Select
ENST00000323777.8	Ensembl	ENSP00000313243.3	6	MANE Select
XM_011524283.2	RefSeq	XP_011522585.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

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

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription factor activity
sequence-specific DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000323777
Coding exons: 6
Length: 68218
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125718
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.60	202	336	0.601	0.0000195	3841
Missense (PolyPhen)		41	95.753	0.42819		1098
Synonymous	1.74	113	139	0.812	0.00000880	1228
Loss of Function	3.86	2	21.1	0.0946	9.71e-7	252

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)	0.0000089	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as a transcriptional factor. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.169
RVIS EVS: 0.02
RVIS percentile EVS: 55.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.140

Gene Damage Prediction

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