HSF4

heat shock transcription factor 4

Basic information

Region (hg38): 16:67164681-67169945

Previous symbols: [ "CTM" ]

Links

ENSG00000102878

∙ NCBI:3299 ∙ OMIM:602438 ∙ HGNC:5227 ∙ Uniprot:Q9ULV5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

cataract 5 multiple types (Definitive), mode of inheritance: AD
total early-onset cataract (Supportive), mode of inheritance: AD
early-onset lamellar cataract (Supportive), mode of inheritance: AD
cataract 5 multiple types (Strong), mode of inheritance: AD
cataract 5 multiple types (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 5, multiple types	AD	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	Ophthalmologic	3233780; 12089525; 18941546; 19014451; 20670914

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSF4 gene.

Cataract_5_multiple_types (83 variants)
Inborn_genetic_diseases (64 variants)
not_provided (30 variants)
HSF4-related_disorder (19 variants)
not_specified (2 variants)
Developmental_cataract (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSF4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001374675.1. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	12 clinvar	2 clinvar	20
missense	5 clinvar	2 clinvar	83 clinvar	13 clinvar	3 clinvar	106
nonsense	3 clinvar	1 clinvar				4
start loss						0
frameshift	4 clinvar	2 clinvar	1 clinvar			7
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar	1 clinvar			5
Total	13	8	91	25	5

Highest pathogenic variant AF is 0.000071893

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSF4	protein_coding	protein_coding	ENST00000264009	13	6561

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.06e-9	0.522	124772	0	104	124876	0.000416

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.651	251	282	0.891	0.0000151	3125
Missense in Polyphen		63	72.023	0.87472		881
Synonymous	0.336	117	122	0.961	0.00000685	1043
Loss of Function	1.16	17	23.0	0.739	0.00000105	253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000784	0.000746
Ashkenazi Jewish	0.000205	0.000199
East Asian	0.00119	0.00117
Finnish	0.000333	0.000278
European (Non-Finnish)	0.000494	0.000459
Middle Eastern	0.00119	0.00117
South Asian	0.000235	0.000196
Other	0.000181	0.000165

dbNSFP

Source: dbNSFP

Function: FUNCTION: DNA-binding protein that specifically binds heat shock promoter elements (HSE). Isoform HSF4A represses transcription while the isoform HSF4B activates transcription. {ECO:0000269|PubMed:16371476}.;
Disease: DISEASE: Cataract 5, multiple types (CTRCT5) [MIM:116800]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT5 includes infantile, lamellar, zonular, nuclear, anterior polar, stellate, and Marner-type cataracts, among others. Finger malformation is observed in some kindreds. {ECO:0000269|PubMed:12089525, ECO:0000269|PubMed:16876512}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.125

Intolerance Scores

loftool: 0.209
rvis_EVS: -0.27
rvis_percentile_EVS: 34.6

Haploinsufficiency Scores

pHI: 0.270
hipred: Y
hipred_score: 0.532
ghis: 0.618

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap
gene_indispensability_pred: E
gene_indispensability_score: 0.965

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Hsf4
Phenotype: vision/eye phenotype;

Zebrafish Information Network

Gene name: hsf4
Affected structure: lens fiber cell
Phenotype tag: abnormal
Phenotype quality: disorganized

Gene ontology

Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;visual perception;positive regulation of cell population proliferation;histone H3-K9 demethylation;cellular response to heat;camera-type eye development;positive regulation of cell differentiation;cell development;positive regulation of transcription from RNA polymerase II promoter in response to heat stress;protein homotrimerization
Cellular component: nucleus;nuclear speck
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;transcription corepressor activity;sequence-specific DNA binding