PZP

PZP alpha-2-macroglobulin like, the group of Alpha-2-macroglobulin family

Basic information

Region (hg38): 12:9148839-9208395

Links

ENSG00000126838 ∙ NCBI:5858 ∙ OMIM:176420 ∙ HGNC:9750 ∙ Uniprot:P20742 ∙ 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 PZP gene.

• Inborn genetic diseases (39 variants)
• not provided (12 variants)
• - (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PZP 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				5	4	9
missense			35	4	1	40
nonsense					1	1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	35	9	7

Variants in PZP

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

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

Position	Type	Phenotype	Significance	ClinVar
12-9150686-A-G			Likely benign (Jun 28, 2018)
12-9150727-C-T		not specified	Uncertain significance (Jun 22, 2023)
12-9151636-T-A		not specified	Uncertain significance (Jul 12, 2023)
12-9152262-C-A		not specified	Uncertain significance (Dec 13, 2023)
12-9152848-C-T		not specified	Uncertain significance (Mar 07, 2024)
12-9153203-T-G		not specified	Uncertain significance (Sep 06, 2022)
12-9153237-G-A		not specified	Uncertain significance (Jan 12, 2024)
12-9154656-A-G		not specified	Likely benign (Feb 09, 2023)
12-9154744-A-T		not specified	Uncertain significance (Jul 11, 2023)
12-9154791-C-G		not specified	Uncertain significance (Mar 01, 2023)
12-9154831-C-T		not specified	Likely benign (Feb 14, 2024)
12-9157208-G-T		not specified	Uncertain significance (May 15, 2023)
12-9157290-G-A			Likely benign (May 01, 2022)
12-9157342-C-T		not specified	Uncertain significance (Sep 16, 2021)
12-9157807-T-C		not specified	Uncertain significance (Apr 04, 2023)
12-9157811-C-T		-	no classification for the single variant (-)
12-9158429-A-G			Benign (Jul 31, 2018)
12-9158460-C-T		not specified	Uncertain significance (Jul 20, 2021)
12-9158518-C-T		not specified	Uncertain significance (Jan 03, 2024)
12-9160380-A-T		not specified	Uncertain significance (Apr 25, 2023)
12-9160460-A-G		not specified	Uncertain significance (Dec 15, 2023)
12-9160461-T-C		not specified	Uncertain significance (Sep 20, 2023)
12-9162647-G-A		not specified	Uncertain significance (Dec 27, 2023)
12-9163767-A-T		not specified	Uncertain significance (Jan 23, 2023)
12-9164145-G-T		not specified	Uncertain significance (Aug 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PZP	protein_coding	protein_coding	ENST00000261336	36	59531

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.82e-36	0.00627	123514	69	2165	125748	0.00892

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.366	756	785	0.963	0.0000396	9634
Missense in Polyphen		262	262.37	0.9986		3401
Synonymous	-0.990	323	301	1.07	0.0000159	2934
Loss of Function	1.73	64	80.8	0.792	0.00000414	961

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0166	0.0166
Ashkenazi Jewish	0.00478	0.00477
East Asian	0.0887	0.0877
Finnish	0.000231	0.000231
European (Non-Finnish)	0.00134	0.00130
Middle Eastern	0.0887	0.0877
South Asian	0.00298	0.00291
Other	0.00425	0.00424

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.

Intolerance Scores

• loftool: 0.988
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.26

Haploinsufficiency Scores

• pHI: 0.136
• hipred: N
• hipred_score: 0.215

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.233

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Gene ontology

• Biological process: female pregnancy;negative regulation of endopeptidase activity
• Cellular component: extracellular region;collagen-containing extracellular matrix;extracellular exosome;blood microparticle
• Molecular function: endopeptidase inhibitor activity;serine-type endopeptidase inhibitor activity