PROZ

Summary

PROZ (protein Z, vitamin K dependent plasma glycoprotein, HGNC:9460) is a protein-coding gene on chromosome 13q34, encoding Vitamin K-dependent protein Z (P22891). Appears to assist hemostasis by binding thrombin and promoting its association with phospholipid vesicles.

This gene encodes a liver vitamin K-dependent glycoprotein that is synthesized in the liver and secreted into the plasma. The encoded protein plays a role in regulating blood coagulation by complexing with protein Z-dependent protease inhibitor to directly inhibit activated factor X at the phospholipid surface. Deficiencies in this protein are associated with an increased risk of ischemic arterial diseases and fetal loss. Mutations in this gene are the cause of protein Z deficiency. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 8858 — RefSeq curated summary.

At a glance

• Gene–disease (curated): protein Z deficiency (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_003891

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9460
Approved symbol	PROZ
Name	protein Z, vitamin K dependent plasma glycoprotein
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	PZ
Ensembl gene	ENSG00000126231
Ensembl biotype	protein_coding
OMIM	176895
Entrez	8858

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 16 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000342783, ENST00000375547, ENST00000493630, ENST00000906454, ENST00000906455, ENST00000906456, ENST00000906457, ENST00000906458, ENST00000906459, ENST00000906460, ENST00000906461, ENST00000906462, ENST00000906463, ENST00000906464, ENST00000906465, ENST00000906466, ENST00000906467

RefSeq mRNA: 2 — MANE Select: NM_003891 NM_001256134, NM_003891

CCDS: CCDS58300, CCDS9531

Canonical transcript exons

ENST00000375547 — 8 exons

Exon	Start	End
ENSE00000862541	113160014	113160177
ENSE00000862544	113160948	113160972
ENSE00000862547	113163009	113163122
ENSE00000862551	113164513	113164644
ENSE00000862556	113170413	113170530
ENSE00000862560	113171594	113172386
ENSE00003641744	113165053	113165120
ENSE00003842625	113158648	113158730

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 96.35.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2133 / max 87.1634, expressed in 25 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136202	0.1382	20
136201	0.0545	13
136203	0.0206	1

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.35	gold quality
liver	UBERON:0002107	89.73	gold quality
adult mammalian kidney	UBERON:0000082	77.21	gold quality
nephron tubule	UBERON:0001231	75.55	silver quality
kidney epithelium	UBERON:0004819	70.97	silver quality
kidney	UBERON:0002113	70.69	gold quality
renal glomerulus	UBERON:0000074	69.29	silver quality
pancreatic ductal cell	CL:0002079	68.61	silver quality
metanephric glomerulus	UBERON:0004736	68.32	silver quality
cortex of kidney	UBERON:0001225	67.98	gold quality
mucosa of transverse colon	UBERON:0004991	67.78	gold quality
right testis	UBERON:0004534	65.82	gold quality
cerebellar hemisphere	UBERON:0002245	65.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	65.38	gold quality
pituitary gland	UBERON:0000007	65.35	gold quality
cerebellar cortex	UBERON:0002129	65.27	gold quality
parotid gland	UBERON:0001831	64.41	gold quality
adenohypophysis	UBERON:0002196	64.25	gold quality
left testis	UBERON:0004533	64.25	gold quality
lower esophagus mucosa	UBERON:0035834	63.59	gold quality
metanephros	UBERON:0000081	63.40	gold quality
cerebellum	UBERON:0002037	63.20	gold quality
tibialis anterior	UBERON:0001385	61.89	silver quality
testis	UBERON:0000473	61.61	gold quality
metanephros cortex	UBERON:0010533	61.53	gold quality
body of pancreas	UBERON:0001150	60.16	gold quality
body of stomach	UBERON:0001161	59.34	gold quality
adult organism	UBERON:0007023	55.76	gold quality
ileal mucosa	UBERON:0000331	55.68	silver quality
granulocyte	CL:0000094	55.59	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A, SP1

miRNA regulators (miRDB)

18 targeting PROZ, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-3974	96.56	66.22	928
HSA-MIR-423-3P	95.99	67.75	62
HSA-MIR-4513	95.04	67.06	727
HSA-MIR-6855-3P	95.04	66.57	725

Literature-anchored findings (GeneRIF, showing 40)

• Weak regulation of protein Z biosynthesis by inflammatory cytokines indicates that it is not a negative acute-phase protein. Plasma PZ concentration is genetically controlled. (PMID:11858503)
• case control studies in humans indicating that diminution of protein Z in factor V Leiden patients aggravates thromboembolic risk (PMID:12297123)
• Low plasma protein Z values were significantly associated with ischemic stroke except in diabetic subjects and females (PMID:12490280)
• enhanced immune-complex formation with protein Z may play a role in unexplained embryo losses (PMID:12623836)
• Blood levels of protein Z measured within 7 days of acute stroke were significantly higher in cases than in controls (geometric mean, 1.46 versus 1.16 microg/mL; P<0.0001, consistent with its importance in ischemic stroke or as an acute phase reactant (PMID:12970515)
• There is a positive correlation between the disease duration and protein Z levels in patients with Behcet’s disease (PMID:14507116)
• PZ levels below 565 ng/mL were associated with ACS (PMID:14652653)
• The A allele of an intron F polymorphism of the PZ gene appears to be a novel protective genetic marker for the risk of cerebral ischemia in young adults. In the context of juvenile stroke, high PZ plasma levels may represent a prothrombotic condition (PMID:14671240)
• protein Z deficiency could be also a risk factor for acute coronary syndromes, early fetal losses, and increased the arterial risk in antiphospholipid syndrome–REVIEW (PMID:15314579)
• Coexpression of E30Q with wild-type protein Z interfered with the secretion of the wild type (PMID:15626740)
• decreased PZ and PS levels are additional risk factors for adverse pregnancy outcome (PMID:15748239)
• data show a progressive increase in protein Z levels with gestational age in normal pregnancies and a return to normal levels around 6 to 12 weeks postpartum (PMID:15841316)
• protein Z may have a role in development of ischemic stroke as shown in polymorphism analysis (PMID:15879328)
• data does not support the hypothesis that protein Z is prothrombotic and the 79A allele is protective for ischemic stroke [letter] (PMID:16120837)
• case control studies indicate that low protein Z level may be another risk factor for retinal vessel occlusion in patients without traditional risk factors for these disorders (PMID:16191090)
• rare alleles of polymorphisms encoding the protein z gene are not significantly associated with ACS (PMID:16807661)
• Linkage analysis for three coagulation factors clustering on chromosome 13q34: factor VII, factor X and protein Z. (PMID:17403098)
• proposed structural model (PMID:17456189)
• A high rate of protein Z deficiency is observed in patients with preeclampsia and fetal demise. (PMID:17701666)
• HNF-4alpha plays a crucial role in human PZ gene expression in hepatocytic cells, and Sp1 is also important (PMID:17958743)
• association between low protein Z levels and the occurrence of PAD. (PMID:18000618)
• The isolated presence of the PZ intron F 79A allele as well as the combination with known thrombophilic risk factors was protective against RPL between the 8th and 12th weeks of gestation. (PMID:18177644)
• Protein Z levels were reduced in patients with chronic kidney disease, and not elevated in patients on haemodialysis (PMID:18180611)
• Intron F G79A polymorphism of PZ gene does not contribute to meaningful diagnostic investigation of thrombophilia in cancer patients (PMID:18246466)
• G79A polymorphism of the PZ gene was shown to be a new independent risk factor for cerebral venous thrombosis (PMID:18677630)
• The median maternal plasma protein Z concentration was significantly lower in patients with pyelonephritis during pregnancy than in patients with normal pregnancies. (PMID:18828054)
• Low PZ levels, but not intron F G79A polymorphism, are associated with unexplained pregnancy loss. (PMID:19026439)
• the ATG haplotype of the protein Zgene is a genetic marker for symptomatic stroke/thromboembolism in white German children (PMID:19050305)
• The frequency of intron F G79A polymorphism of protein Z gene was higher in patients than controls, and carrying 79 AA genotype could be a risk factor for severe sepsis and septic shock. (PMID:19124455)
• Haplotypic or genotypic combinations of three protein Z polymorphisms influence protein Z plasma level. (PMID:19132212)
• Protein Z g-42a variant and the risk of pregnancy-related venous thromboembolism in a cohort of Italian patients. (PMID:19185907)
• the difference observed in secretion patterns of protein Z and factor X was mainly based on the structure of their gamma-carboxyglutamic acid domains. (PMID:19188667)
• plasma level is not a key player in the pathophysiology of premature coronary artery disease; rare genotypes of PZ gene were found to be associated with premature coronary artery disease (PMID:19572077)
• The distribution of allele and genotype frequencies of Protein Z A-13G and G79A polymorphisms did not differ significantly between Behcets disease patients and controls; no associations between thrombotic events protein Z gene polymorphisms (PMID:19796528)
• PROTEIN A AND PZI WERE FOUND IN KIDNEY TUBULES BY IMMUNOHISTOCHEMISTRY (PMID:20024489)
• Results of this meta-analysis are consistent with a role for protein Z deficiency in thrombotic diseases, including arterial thrombosis, pregnancy complications and venous thromboembolism. (PMID:20076855)
• Premature newborns suffering from respiratory distress syndrome showed decreased serum protein Z levels than normal preterm control newborns with further increase in its pattern after recovery. (PMID:20180321)
• the roles of PZ plasma level and PZ gene polymorphisms remain debated with conflicting results in arterial, venous, or placental thrombosis (PMID:20416992)
• Data show that mutation of four ZPI contact residues eliminated PZ binding and membrane-dependent PZ acceleration of fXa inhibition. (PMID:20427285)
• Low PZ levels are associated with the pathobiology of HELLP syndrome. (PMID:20460354)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	proza	ENSDARG00000037783
danio_rerio	prozb	ENSDARG00000076900
mus_musculus	Proz	ENSMUSG00000031445
rattus_norvegicus	Proz	ENSRNOG00000019700
drosophila_melanogaster	CG32834	FBGN0052834
drosophila_melanogaster	CG34043	FBGN0054043

Paralogs (1): PROC (ENSG00000115718)

Protein

Protein identifiers

Vitamin K-dependent protein Z — P22891 (reviewed: P22891)

All UniProt accessions (1): P22891

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with SERPINA10.

Subcellular location. Secreted.

Tissue specificity. Plasma.

Post-translational modifications. The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.

Similarity. Belongs to the peptidase S1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P22891-1	1	yes
P22891-2	2

RefSeq proteins (2): NP_001243063, NP_003882* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000294	GLA_domain	Domain
IPR000742	EGF	Domain
IPR001254	Trypsin_dom	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR012224	Pept_S1A_FX	Family
IPR017857	Coagulation_fac-like_Gla_dom	Homologous_superfamily
IPR035972	GLA-like_dom_SF	Homologous_superfamily
IPR043504
IPR050442	Peptidase_S1_coag_factors	Family

Pfam: PF00008, PF00089, PF00594, PF14670

UniProt features (74 total): strand 24, modified residue 14, disulfide bond 9, helix 7, glycosylation site 6, domain 4, turn 4, sequence variant 2, signal peptide 1, propeptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3F1S	X-RAY DIFFRACTION	2.3
3H5C	X-RAY DIFFRACTION	3.26

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22891-F1	85.39	0.59

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (14): 55, 57, 60, 61, 66, 67, 70, 73, 75, 80, 104, 47, 48, 51

Disulfide bonds (9): 58–63, 91–102, 96–111, 113–122, 129–141, 137–150, 152–165, 203–219, 327–341

Glycosylation sites (6): 93, 99, 225, 233, 306, 332

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-159740	Gamma-carboxylation of protein precursors
R-HSA-159763	Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
R-HSA-159782	Removal of aminoterminal propeptides from gamma-carboxylated proteins
R-HSA-9769739	Regulation of clotting cascade

MSigDB gene sets: 74 (showing top): MODULE_172, GOBP_WOUND_HEALING, REACTOME_GAMMA_CARBOXYLATION_TRANSPORT_AND_AMINO_TERMINAL_CLEAVAGE_OF_PROTEINS, MODULE_109, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, chr13q34, MODULE_113, GOBP_HEMOSTASIS, MODULE_209, GOBP_REGULATION_OF_BODY_FLUID_LEVELS, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, MODULE_107, GOBP_PROTEOLYSIS, GOCC_GOLGI_LUMEN, GOMF_PEPTIDASE_ACTIVITY

GO Biological Process (3): proteolysis (GO:0006508), blood coagulation (GO:0007596), hemostasis (GO:0007599)

GO Molecular Function (3): serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	3
Coagulation pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular organelle lumen	2
protein metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
regulation of body fluid levels	1
endopeptidase activity	1
serine-type peptidase activity	1
metal ion binding	1
binding	1
endoplasmic reticulum	1
Golgi apparatus	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

936 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PROZ	SERPINA10	Q9UK55	928
PROZ	CTSG	P08311	557
PROZ	F13B	P05160	537
PROZ	PLAT	P00750	529
PROZ	CRP	P02741	521
PROZ	ELANE	P08246	491
PROZ	LCAT	P04180	490
PROZ	DEFB124	Q8NES8	468
PROZ	SIRT1	Q96EB6	444
PROZ	FGG	P02679	442
PROZ	PPARGC1A	Q9UBK2	440
PROZ	GALNT13	Q8IUC8	415
PROZ	CHST13	Q8NET6	407
PROZ	SERPIND1	P05546	396
PROZ	OR5M11	Q96RB7	394

IntAct

12 interactions, top by confidence:

A	B	Type	Score
SERPINA10	PROZ	psi-mi:“MI:0407”(direct interaction)	0.650
OR52W1	PROZ	psi-mi:“MI:0915”(physical association)	0.400
PROZ	MAP2K7	psi-mi:“MI:0914”(association)	0.350
IP6K3	PROZ	psi-mi:“MI:0914”(association)	0.350
PROZ	IDE	psi-mi:“MI:0914”(association)	0.350

BioGRID (57): FOXG1 (Affinity Capture-MS), INTS6 (Affinity Capture-MS), PROZ (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), FOXF2 (Affinity Capture-MS), PROZ (Affinity Capture-MS), SIPA1L2 (Affinity Capture-MS), SDF2L1 (Affinity Capture-MS), SIK2 (Affinity Capture-MS), MAP2K7 (Affinity Capture-MS), CDC6 (Affinity Capture-MS), SENP1 (Affinity Capture-MS), RICTOR (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TYW3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVH4, A1L453, A4D1T9, A6H6T1, A8MTI9, A8QL53, A8QL57, B5U6Y3, E5RG02, O35453, O70169, P00745, P04070, P08709, P0CG03, P0DJE9, P22891, Q14BX2, Q28278, Q28661, Q2F9P2, Q2F9P4, Q2TV78, Q3V0Q7, Q402U7, Q4R7Y7, Q5FBW1, Q5M8S2, Q6AXZ6, Q6AY28, Q6IE62, Q6IE63, Q6PEW0, Q6UWB4, Q76HL1, Q7M756, Q7M761, Q7RTY5, Q7RTY7, Q7Z5A4

Diamond homologs: A6MFK7, A6MFK8, B5G6G5, O00187, O15393, O18783, O19045, O88947, O97399, P00734, P00735, P00740, P00741, P00742, P00743, P00745, P00747, P00760, P03952, P04070, P06867, P08709, P12545, P14272, P16291, P16292, P16293, P16294, P16295, P16296, P17538, P19221, P19540, P22457, P22891, P25155, P26262, P28175, P29786, P29787

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GGCX	“up-regulates activity”	PROZ	carboxylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

43 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1290 predictions. Top by Δscore:

Variant	Effect	Δscore
13:113160012:A:AG	acceptor_gain	1.0000
13:113160013:G:GA	acceptor_gain	1.0000
13:113160013:GT:G	acceptor_gain	1.0000
13:113160151:G:GT	donor_gain	1.0000
13:113160166:G:GT	donor_gain	1.0000
13:113160170:T:TA	donor_gain	1.0000
13:113160171:A:AA	donor_gain	1.0000
13:113160178:G:GG	donor_gain	1.0000
13:113170408:TAAA:T	acceptor_loss	1.0000
13:113170409:A:AG	acceptor_gain	1.0000
13:113170411:A:AC	acceptor_loss	1.0000
13:113170526:AACAT:A	donor_gain	1.0000
13:113170527:ACAT:A	donor_gain	1.0000
13:113170528:CAT:C	donor_gain	1.0000
13:113170529:AT:A	donor_gain	1.0000
13:113170531:G:GG	donor_gain	1.0000
13:113171591:CAGA:C	acceptor_loss	1.0000
13:113171592:A:AG	acceptor_gain	1.0000
13:113171593:G:GC	acceptor_gain	1.0000
13:113171593:GA:G	acceptor_gain	1.0000
13:113171593:GAT:G	acceptor_gain	1.0000
13:113171593:GATT:G	acceptor_gain	1.0000
13:113171593:GATTT:G	acceptor_gain	1.0000
13:113158727:TCAGG:T	donor_loss	0.9900
13:113158728:CAGG:C	donor_loss	0.9900
13:113158729:AGGTA:A	donor_loss	0.9900
13:113158731:G:C	donor_loss	0.9900
13:113158732:T:A	donor_loss	0.9900
13:113160011:TA:T	acceptor_loss	0.9900
13:113160012:AGTAT:A	acceptor_loss	0.9900

AlphaMissense

2611 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:113160115:T:A	C58S	0.991
13:113160116:G:C	C58S	0.991
13:113171998:T:C	F366L	0.991
13:113172000:T:A	F366L	0.991
13:113172000:T:G	F366L	0.991
13:113160130:T:A	C63S	0.986
13:113160131:G:C	C63S	0.986
13:113163113:T:A	C122S	0.986
13:113163114:G:C	C122S	0.986
13:113170420:T:C	L194S	0.986
13:113171999:T:G	F366C	0.986
13:113163053:T:A	C102S	0.983
13:113163054:G:C	C102S	0.983
13:113164548:T:A	C137S	0.983
13:113164549:G:C	C137S	0.983
13:113160954:T:C	F81L	0.982
13:113160956:C:A	F81L	0.982
13:113160956:C:G	F81L	0.982
13:113163035:T:A	C96S	0.982
13:113163036:G:C	C96S	0.982
13:113164524:T:A	C129S	0.982
13:113164525:G:C	C129S	0.982
13:113160131:G:A	C63Y	0.981
13:113164593:T:A	C152S	0.981
13:113164594:G:C	C152S	0.981
13:113160955:T:G	F81C	0.980
13:113164632:T:A	C165S	0.980
13:113164633:G:C	C165S	0.980
13:113163080:T:A	C111S	0.979
13:113163081:G:C	C111S	0.979

dbSNP variants (sampled 300 via entrez): RS1000010267 (13:113168752 C>A,T), RS1000108535 (13:113172870 C>A), RS1000235355 (13:113163361 T>C,G), RS1000373319 (13:113161578 G>A), RS1000912999 (13:113172474 G>A), RS1000920722 (13:113165994 A>G), RS1001102485 (13:113157126 T>C), RS1001282212 (13:113167672 T>A), RS1001309095 (13:113166271 G>A), RS1001325874 (13:113160650 G>T), RS1002323617 (13:113164798 G>C), RS1002331555 (13:113159423 G>T), RS1002443926 (13:113162771 C>G), RS1002770719 (13:113160885 A>G,T), RS1002935163 (13:113164055 T>C)

Disease associations

OMIM: gene MIM:176895 | disease phenotypes: MIM:614024

GenCC curated gene-disease

Disease	Classification	Inheritance
protein Z deficiency	Limited	Unknown

Mondo (2): protein Z deficiency (MONDO:0013532), thrombocytopenia (MONDO:0002049)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000082_1	Factor VII	5.000000e-16
GCST005721_3	Food allergy (parent-of-origin effect)	4.000000e-06
GCST008103_78	Bipolar disorder	1.000000e-06
GCST90002406_414	Reticulocyte fraction of red cells	1.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004619	factor VII measurement
EFO:0005939	parental genotype effect measurement
EFO:0007016	food allergy measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Rosiglitazone	decreases expression	1
Arsenic	affects methylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	decreases expression	1
Malathion	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

240 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT