Gene:
PROC
protein C (inactivator of coagulation factors Va and VIIIa)

PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.


Annotated Labels

  1. FDA Label for warfarin and CYP2C9,PROC,PROS1,VKORC1
  2. HCSC Label for drospirenone,ethinyl estradiol and F5,PROC,PROS1,SERPINC1
  3. HCSC Label for ethinyl estradiol,norelgestromin and F2,F5,MTHFR,PROC,PROS1,SERPINC1

last updated 07/14/2014

1. FDA Label for warfarin and CYP2C9,PROC,PROS1,VKORC1

Actionable PGx

Summary

Warfarin (Coumadin) is an anticoagulant used as a prophylaxis and to treat venous thrombosis, pulmonary embolism, thromboembolic complications from atrial fibrillationa and cardiac valve replacement, and to reduce the recurrence of myocardial infarction. Pharmacogenomics-related dosing information for CYP2C9 and VKORC1 variants is provided within the label. The drug label notes that deficiency in protein C (PROC) or protein S (PROS1) have been associated with tissue necrosis following warfarin administration.

There's more of this label. Read more.


2. HCSC Label for drospirenone,ethinyl estradiol and F5,PROC,PROS1,SERPINC1

Actionable PGx

Summary

The product monograph for drospirenone and ethinyl estradiol (YAZ) states that the drug is contraindicated in women with Factor V Leiden mutation, antithrombin-III-deficiency, protein C deficiency and protein S deficiency (among other contraindications), due to the risk for arterial or venous thrombosis.

There's more of this label. Read more.


3. HCSC Label for ethinyl estradiol,norelgestromin and F2,F5,MTHFR,PROC,PROS1,SERPINC1

Actionable PGx

Summary

The product monograph for norelgestromin and ethinyl estradiol (EVRA) states that the drug is contraindicated in women with Factor V Leiden mutation, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinaemia due to mutations in the MTHFR gene and prothrombin mutation G20210A (among other contraindications), due to the risk for arterial or venous thrombosis.

There's more of this label. Read more.


PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

List of all variant annotations for PROC

Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
rs1799808 NC_000002.11:g.128175862C>T, NC_000002.12:g.127418286C>T, NG_016323.1:g.4867C>T, NM_000312.3:c.-228C>T, XM_005263715.1:c.-161C>T, XM_005263715.3:c.-161C>T, XM_005263716.1:c.-161C>T, XM_005263716.3:c.-161C>T, XM_005263717.1:c.-161C>T, XM_005263717.3:c.-161C>T, rs59400154
C > T
SNP
rs1799809 NC_000002.11:g.128175875G>A, NC_000002.12:g.127418299G>A, NG_016323.1:g.4880G>A, NM_000312.3:c.-215G>A, XM_005263715.1:c.-148G>A, XM_005263715.3:c.-148G>A, XM_005263716.1:c.-148G>A, XM_005263716.3:c.-148G>A, XM_005263717.1:c.-148G>A, XM_005263717.3:c.-148G>A, rs59122016
G > A
SNP
rs2069919 NC_000002.11:g.128179553G>A, NC_000002.12:g.127421977G>A, NG_016323.1:g.8558G>A, NM_000312.3:c.237+528G>A, XM_005263715.1:c.420+528G>A, XM_005263715.3:c.420+528G>A, XM_005263716.1:c.300+528G>A, XM_005263716.3:c.300+528G>A, XM_005263717.1:c.300+528G>A, XM_005263717.3:c.300+528G>A, rs57786626
G > A
SNP
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Alternate Names:  prepro-protein C
Alternate Symbols:  None
PharmGKB Accession Id: PA33799

Details

Cytogenetic Location: chr2 : q13 - q14.3
GP mRNA Boundary: chr2 : 128175996 - 128186822
GP Gene Boundary: chr2 : 128165996 - 128189822
Strand: plus

Visualization

UCSC has a Genome Browser that you can use to view PharmGKB annotations for this gene in context with many other sources of information.

View on UCSC Browser
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Warfarin Pathway, Pharmacodynamics
    Simplified diagram of the target of warfarin action and downstream genes and effects.

Curated Information ?

Evidence Gene
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
GGCX

Curated Information ?

Curated Information ?

Publications related to PROC: 6

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters. European journal of clinical pharmacology. 2011. Geisen Christof, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients. Clinical pharmacology and therapeutics. 2010. Pautas E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic determinants of warfarin dosing in the Han-Chinese population. Pharmacogenomics. 2009. Lee M T Michael, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association of warfarin dose with genes involved in its action and metabolism. Human genetics. 2007. Wadelius Mia, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin. Thrombosis and haemostasis. 2005. Rost Simone, et al. PubMed

LinkOuts

NCBI Gene:
5624
OMIM:
176860
612283
612304
UCSC Genome Browser:
NM_000312
RefSeq RNA:
NM_000312
RefSeq Protein:
NP_000303
RefSeq DNA:
NG_016323
NT_022135
UniProtKB:
PROC_HUMAN (P04070)
Ensembl:
ENSG00000115718
GenAtlas:
PROC
GeneCard:
PROC
MutDB:
PROC
ALFRED:
LO133899H
HuGE:
PROC
Comparative Toxicogenomics Database:
5624
ModBase:
P04070
HumanCyc Gene:
HS03931
HGNC:
9451

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