PROZ

protein Z, vitamin K dependent plasma glycoprotein, the group of Gla domain containing

Basic information

Region (hg38): 13:113158648-113172386

Links

ENSG00000126231 ∙ NCBI:8858 ∙ OMIM:176895 ∙ HGNC:9460 ∙ Uniprot:P22891 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• protein Z deficiency (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Protein Z deficiency	AD	General	There is weak or mixed evidence that protein Z deficiency has an adverse health effect	General	7495103; 10829076; 11289354; 11895801; 15638861; 14671240; 15626740; 16938126; 20076855

ClinVar

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

• not_specified (67 variants)
• not_provided (7 variants)
• Protein_Z_deficiency (5 variants)
• PROZ-related_disorder (3 variants)
• Thrombocytopenia (1 variants)
• Abnormal_bleeding (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PROZ gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003891.3. 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				1	3	4
missense			67	7	1	75
nonsense						0
start loss						0
frameshift			1	1		2
splice donor/acceptor (+/-2bp)						0
Total	0	0	68	9	4

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PROZ	protein_coding	protein_coding	ENST00000342783	9	13727

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.18e-16	0.00149	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0555	257	255	1.01	0.0000156	2727
Missense in Polyphen		84	88.044	0.95407		1032
Synonymous	0.380	101	106	0.953	0.00000742	826
Loss of Function	-0.900	22	17.9	1.23	9.65e-7	197

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000626	0.000626
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000246	0.000246
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Appears to assist hemostasis by binding thrombin and promoting its association with phospholipid vesicles. Inhibits activity of the coagulation protease factor Xa in the presence of SERPINA10, calcium and phospholipids.
• Pathway: Warfarin Pathway, Pharmacodynamics;Post-translational protein modification;Metabolism of proteins;Gamma-carboxylation of protein precursors;Removal of aminoterminal propeptides from gamma-carboxylated proteins;Gamma-carboxylation, transport, and amino-terminal cleavage of proteins;Gamma carboxylation, hypusine formation and arylsulfatase activation (Consensus)

Recessive Scores

• pRec: 0.257

Intolerance Scores

• loftool: 0.261
• rvis_EVS: -0.24
• rvis_percentile_EVS: 36.17

Haploinsufficiency Scores

• pHI: 0.109
• hipred: N
• hipred_score: 0.123
• ghis: 0.397

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.310

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Proz
• Phenotype: homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: proteolysis;endoplasmic reticulum to Golgi vesicle-mediated transport;blood coagulation
• Cellular component: extracellular space;endoplasmic reticulum lumen;Golgi lumen;extracellular exosome
• Molecular function: serine-type endopeptidase activity;calcium ion binding