PCSK4

proprotein convertase subtilisin/kexin type 4, the group of Proprotein convertase subtilisin/kexin family

Basic information

Region (hg38): 19:1481428-1490752

Links

ENSG00000115257 ∙ NCBI:54760 ∙ OMIM:600487 ∙ HGNC:8746 ∙ Uniprot:Q6UW60 ∙ 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 PCSK4 gene.

• not_specified (159 variants)
• not_provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCSK4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017573.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense			153	6	1	160
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	153	8	1

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCSK4	protein_coding	protein_coding	ENST00000300954	15	9325

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.34e-12	0.759	125638	1	89	125728	0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0360	497	495	1.00	0.0000348	4728
Missense in Polyphen		195	201.61	0.96722		1936
Synonymous	-1.76	267	233	1.15	0.0000186	1568
Loss of Function	1.73	24	35.0	0.685	0.00000188	335

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000937	0.000884
Ashkenazi Jewish	0.00289	0.00278
East Asian	0.000112	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000307	0.000281
Middle Eastern	0.000112	0.000109
South Asian	0.000297	0.000294
Other	0.000347	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues (By similarity). In males, important for ADAM2 processing as well as other acrosomal proteins with roles in fertilization and critical for normal fertilization events such as sperm capacitation, acrosome reaction and binding of sperm to zona pellucida (By similarity). Plays also a role in female fertility, involved in the regulation of trophoblast migration and placental development, may be through the proteolytical processing and activation of proteins such as IGF2 (PubMed:16040806). May also participate in folliculogenesis in the ovaries (By similarity). {ECO:0000250|UniProtKB:P29121, ECO:0000269|PubMed:16040806}.

Recessive Scores

• pRec: 0.129

Intolerance Scores

• loftool: 0.235
• rvis_EVS: 0.61
• rvis_percentile_EVS: 82.93

Haploinsufficiency Scores

• pHI: 0.0995
• hipred: N
• hipred_score: 0.170
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.368

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pcsk4
• Phenotype: homeostasis/metabolism phenotype; reproductive system phenotype

Gene ontology

• Biological process: binding of sperm to zona pellucida;acrosome reaction;fertilization;protein processing;peptide hormone processing;reproductive process;sperm capacitation
• Cellular component: acrosomal vesicle;acrosomal membrane;trans-Golgi network;membrane;integral component of membrane;integral component of Golgi membrane
• Molecular function: serine-type endopeptidase activity;protein binding