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 (6 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.

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			2	10	2	14
missense	1	1	52	8	3	65
nonsense	2	1				3
start loss						0
frameshift	2	1	1			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	2	2			5
splice region			3	3		6
non coding			3	10	4	17
Total	6	5	61	28	9

Highest pathogenic variant AF is 0.0000723

Variants in HSF4

This is a list of pathogenic ClinVar variants found in the HSF4 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-67164687-C-T		Cataract 5 multiple types	Benign (Jan 12, 2018)
16-67164789-C-T		Cataract 5 multiple types	Benign (Jan 13, 2018)
16-67164818-G-T		HSF4-related disorder	Likely pathogenic (Sep 01, 2022)
16-67164819-A-G		Cataract 5 multiple types • HSF4-related disorder	Uncertain significance (May 04, 2022)
16-67164843-A-G		Cataract 5 multiple types	Uncertain significance (Jan 13, 2018)
16-67164844-G-T		Cataract 5 multiple types	Uncertain significance (Jul 28, 2023)
16-67164851-C-A		Cataract 5 multiple types	Uncertain significance (Jan 12, 2024)
16-67164867-C-A		Cataract 5 multiple types	Pathogenic (Jul 01, 2002)
16-67164874-C-A		Cataract 5 multiple types	Benign/Likely benign (Mar 01, 2022)
16-67164880-G-T		Cataract 5 multiple types	Pathogenic (Mar 09, 2022)
16-67164892-G-A		Cataract 5 multiple types	Likely benign (Aug 06, 2020)
16-67164899-GA-G		Cataract 5 multiple types	Pathogenic (Nov 09, 2017)
16-67164901-C-T			Likely benign (May 15, 2018)
16-67164903-C-T		Inborn genetic diseases	Uncertain significance (Jun 26, 2023)
16-67164915-A-G		Cataract 5 multiple types	Uncertain significance (Jan 13, 2018)
16-67164943-C-T		not specified • Cataract 5 multiple types	Benign (Jan 26, 2024)
16-67165456-C-G			Benign (Oct 02, 2018)
16-67165554-C-A		not specified	Uncertain significance (Aug 18, 2022)
16-67165555-C-T		Inborn genetic diseases	Uncertain significance (Jun 22, 2023)
16-67165585-T-C			Uncertain significance (Oct 19, 2023)
16-67165588-A-G		Developmental cataract	Likely pathogenic (May 01, 2021)
16-67165593-T-A		Cataract 5 multiple types	Uncertain significance (May 22, 2022)
16-67165597-A-G		Cataract 5 multiple types	Uncertain significance (Sep 15, 2019)
16-67165601-T-C		Cataract 5 multiple types • Inborn genetic diseases	Uncertain significance (Mar 29, 2022)
16-67165612-G-A		Inborn genetic diseases	Uncertain significance (Jul 11, 2023)

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
• 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