PCSK1N

proprotein convertase subtilisin/kexin type 1 inhibitor, the group of Granins

Basic information

Region (hg38): X:48831095-48835610

Links

ENSG00000102109 ∙ NCBI:27344 ∙ OMIM:300399 ∙ HGNC:17301 ∙ Uniprot:Q9UHG2 ∙ 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 PCSK1N gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCSK1N 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			24			24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	24	0	0

Variants in PCSK1N

This is a list of pathogenic ClinVar variants found in the PCSK1N region.

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

Position	Type	Phenotype	Significance	ClinVar
X-48831267-G-A		not specified	Uncertain significance (Feb 28, 2024)
X-48831297-G-A		not specified	Uncertain significance (Apr 25, 2023)
X-48831300-G-A		not specified	Uncertain significance (May 30, 2024)
X-48831307-C-G		not specified	Uncertain significance (Dec 01, 2022)
X-48831391-G-A		not specified	Uncertain significance (Nov 30, 2022)
X-48831412-C-A		not specified	Uncertain significance (Apr 13, 2022)
X-48831419-G-C		not specified	Uncertain significance (Nov 19, 2022)
X-48831441-C-A		not specified	Uncertain significance (Sep 06, 2022)
X-48831879-C-T		not specified	Uncertain significance (Sep 29, 2023)
X-48831891-C-A		not specified	Uncertain significance (Dec 15, 2022)
X-48831984-G-A		not specified	Uncertain significance (Mar 25, 2024)
X-48831990-G-C		not specified	Uncertain significance (Jan 16, 2024)
X-48832002-C-T		not specified	Uncertain significance (Nov 22, 2021)
X-48832004-G-T		not specified	Uncertain significance (Jan 26, 2022)
X-48832014-C-T		not specified	Uncertain significance (Oct 25, 2023)
X-48832053-G-T		not specified	Uncertain significance (Mar 31, 2024)
X-48832068-C-G		not specified	Uncertain significance (Sep 30, 2022)
X-48832077-C-A		not specified	Uncertain significance (May 10, 2024)
X-48832080-C-G		not specified	Uncertain significance (Mar 01, 2024)
X-48832106-C-A		not specified	Uncertain significance (Jan 22, 2024)
X-48832142-A-G		not specified	Uncertain significance (Nov 03, 2022)
X-48832143-C-G		not specified	Uncertain significance (Oct 03, 2022)
X-48832169-T-G		not specified	Uncertain significance (Feb 07, 2023)
X-48832236-C-T		not specified	Uncertain significance (Apr 20, 2023)
X-48832289-G-A		not specified	Uncertain significance (Feb 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCSK1N	protein_coding	protein_coding	ENST00000218230	3	4532

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.532	0.413	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.813	42	59.7	0.704	0.00000459	1513
Missense in Polyphen		17	31.839	0.53394		799
Synonymous	1.31	20	29.0	0.689	0.00000230	646
Loss of Function	1.38	0	2.23	0.00	1.45e-7	65

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function in the control of the neuroendocrine secretory pathway. Proposed be a specific endogenous inhibitor of PCSK1. ProSAAS and Big PEN-LEN, both containing the C-terminal inhibitory domain, but not the further processed peptides reduce PCSK1 activity in the endoplasmic reticulum and Golgi. It reduces the activity of the 84 kDa form but not the autocatalytically derived 66 kDa form of PCSK1. Subsequent processing of proSAAS may eliminate the inhibition. Slows down convertase-mediated processing of proopiomelanocortin and proenkephalin. May control the intracellular timing of PCSK1 rather than its total level of activity. The function of the processed secreted peptides is not known (By similarity). {ECO:0000250}.

Recessive Scores

• pRec: 0.112

Haploinsufficiency Scores

• pHI: 0.135
• hipred: N
• hipred_score: 0.324
• ghis: 0.506

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pcsk1n
• Phenotype: digestive/alimentary phenotype; vision/eye phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: response to dietary excess;neuropeptide signaling pathway;response to cold;negative regulation of endopeptidase activity;peptide hormone processing
• Cellular component: extracellular space;trans-Golgi network;secretory granule
• Molecular function: endopeptidase inhibitor activity;serine-type endopeptidase inhibitor activity;signaling receptor binding