HTRA4

HtrA serine peptidase 4, the group of PDZ domain containing

Basic information

Region (hg38): 8:38974228-38988663

Links

ENSG00000169495 ∙ NCBI:203100 ∙ OMIM:610700 ∙ HGNC:26909 ∙ Uniprot:P83105 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HTRA4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HTRA4 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						0
missense			38	3		41
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	38	3	0

Variants in HTRA4

This is a list of pathogenic ClinVar variants found in the HTRA4 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-38974273-C-T		not specified	Uncertain significance (Dec 27, 2023)
8-38974291-G-A		not specified	Uncertain significance (Dec 22, 2024)
8-38974339-G-A		not specified	Uncertain significance (Nov 23, 2024)
8-38974352-G-A		not specified	Likely benign (Jun 04, 2024)
8-38974378-T-A		not specified	Uncertain significance (Jan 18, 2025)
8-38974390-G-A		not specified	Uncertain significance (Mar 11, 2024)
8-38974418-T-C		not specified	Uncertain significance (Oct 23, 2024)
8-38974445-C-T		not specified	Uncertain significance (May 15, 2024)
8-38974471-C-G		not specified	Uncertain significance (Jun 22, 2021)
8-38974489-G-A		not specified	Uncertain significance (Apr 12, 2022)
8-38974504-G-C		not specified	Uncertain significance (Sep 14, 2023)
8-38974510-G-A		not specified	Uncertain significance (Jan 23, 2024)
8-38974532-C-T		not specified	Uncertain significance (Jan 10, 2023)
8-38974562-C-T		not specified	Uncertain significance (Oct 02, 2023)
8-38974604-C-T		not specified	Uncertain significance (Nov 08, 2022)
8-38974623-G-C		not specified	Uncertain significance (Jul 06, 2021)
8-38974640-T-A		not specified	Uncertain significance (Aug 14, 2024)
8-38974654-G-A		not specified	Likely benign (Jul 28, 2021)
8-38974654-G-T		not specified	Uncertain significance (Aug 07, 2024)
8-38974657-G-A		not specified	Uncertain significance (Mar 07, 2025)
8-38974666-G-T		not specified	Uncertain significance (Oct 29, 2021)
8-38974676-G-C		not specified	Uncertain significance (Jul 26, 2021)
8-38974684-A-G		not specified	Uncertain significance (Oct 17, 2024)
8-38974710-G-T		not specified	Uncertain significance (Aug 16, 2021)
8-38974711-G-A		not specified	Uncertain significance (May 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HTRA4	protein_coding	protein_coding	ENST00000302495	9	14499

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.27e-12	0.0679	124963	4	781	125748	0.00313

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.968	206	249	0.827	0.0000136	3003
Missense in Polyphen		73	92.304	0.79086		1194
Synonymous	1.10	92	106	0.865	0.00000642	1011
Loss of Function	0.372	19	20.8	0.912	0.00000121	230

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00555	0.00556
Ashkenazi Jewish	0.00	0.00
East Asian	0.000598	0.000598
Finnish	0.0116	0.0115
European (Non-Finnish)	0.00349	0.00345
Middle Eastern	0.000598	0.000598
South Asian	0.000363	0.000359
Other	0.00279	0.00277

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine protease. {ECO:0000305}.

Recessive Scores

• pRec: 0.0719

Intolerance Scores

• loftool: 0.399
• rvis_EVS: 0.6
• rvis_percentile_EVS: 82.66

Haploinsufficiency Scores

• pHI: 0.0379
• hipred: N
• hipred_score: 0.208

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0793

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Htra4
• Phenotype: hearing/vestibular/ear phenotype

Gene ontology

• Biological process: regulation of cell growth;proteolysis;negative regulation of transforming growth factor beta receptor signaling pathway
• Cellular component: extracellular region
• Molecular function: endopeptidase activity;serine-type endopeptidase activity;insulin-like growth factor binding