Affinage

PROC

Vitamin K-dependent protein C · UniProt P04070

Length
461 aa
Mass
52.1 kDa
Annotated
2026-04-28
99 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PROC encodes protein C, a vitamin K-dependent serine protease zymogen that functions as a critical anticoagulant by inactivating coagulation factors Va and VIIIa, thereby suppressing thrombin generation. Hepatic transcription of PROC is governed by promoter polymorphisms that modulate expression levels and by an intron 1 enhancer element where the transcription factor HNF-1 exerts a repressive effect (PMID:7548679, PMID:11140943). Missense mutations in the protease domain cause protein C deficiency through two principal mechanisms: impaired secretion due to intracellular retention of misfolded protein (type I deficiency) and reduced catalytic efficiency with increased Km and decreased Vmax (type II deficiency) (PMID:12362235, PMID:39743273, PMID:22817391). Splice-site and deep intronic mutations produce aberrant mRNA isoforms—including exon skipping, intron retention, and pseudo-exon inclusion—that are subject to nonsense-mediated mRNA decay or encode nonfunctional protein, and these defects can be partially rescued by engineered U1/U7 snRNAs (PMID:8822578, PMID:40789311, PMID:41791661).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1993 Low

    The question of which protein C domains are essential for anticoagulant function was addressed by identifying a Gla domain missense mutation (Arg15Trp) that dissociates antigen levels from anticoagulant activity, implicating the Gla domain pentapeptide in calcium-dependent membrane binding required for function.

    Evidence DNA sequencing and family co-segregation analysis in a protein C-deficient kindred

    PMID:8499568

    Open questions at the time
    • No in vitro functional assay to confirm membrane-binding defect
    • Single family study without independent replication
    • No direct calcium-binding or phospholipid-binding measurement
  2. 1995 Medium

    How promoter sequence variation controls PROC expression was unknown; linked diallelic promoter polymorphisms were shown to cause a ≥2-fold difference in transcriptional output in hepatoma cells, establishing that common promoter haplotypes are a determinant of protein C plasma levels.

    Evidence Transient transfection of PROC promoter-luciferase reporters in HepG2 cells

    PMID:7548679

    Open questions at the time
    • Relevant transcription factors binding differentially to haplotypes not identified
    • In vivo relevance in human liver not confirmed
    • Effect size in plasma protein C levels not quantified in population studies
  3. 1996 Medium

    It was unclear how premature termination codon mutations in PROC affect mRNA abundance; RT-PCR of patient lymphocytes demonstrated allelic exclusion (nonsense-mediated decay) of mutant PROC transcripts for most null alleles, while a 2-bp insertion instead activated a cryptic splice site generating aberrant mRNA, revealing two distinct mRNA-level pathogenic mechanisms.

    Evidence RT-PCR and direct sequencing of ectopic PROC transcripts from patient lymphocytes with polymorphism-based allele discrimination

    PMID:8822578

    Open questions at the time
    • NMD pathway components responsible not identified
    • Analysis performed on ectopic (lymphocyte) transcripts rather than hepatic mRNA
    • Quantitative contribution of NMD vs. residual mutant transcript not measured
  4. 2000 Medium

    Regulatory elements beyond the core promoter were uncharacterized; an intronic enhancer in intron 1 (142 bp essential region) was identified that boosts hepatic promoter activity, and HNF-1 was shown to repress rather than activate transcription when this element is present, revising the expected role of HNF-1 at the PROC locus.

    Evidence Deletion mapping of PROC promoter-luciferase reporters in human hepatoma cells with HNF-1 perturbation

    PMID:11140943

    Open questions at the time
    • HNF-1 repressive mechanism (direct binding vs. indirect) not resolved
    • In vivo chromatin context not assessed
    • Other transcription factors acting on the intronic enhancer not identified
  5. 2002 Medium

    The molecular basis of type I protein C deficiency from missense mutations was unclear; expression of the D180G protease-domain variant revealed a 79% secretion deficit with normal intracellular protein, establishing misfolding-driven intracellular retention as a primary pathogenic mechanism.

    Evidence Transient expression of PROC mutant in HK-293 cells with ELISA quantification of secreted vs. intracellular protein; structural modelling on the APC crystal structure

    PMID:12362235

    Open questions at the time
    • Degradation pathway (proteasomal vs. lysosomal) not determined
    • ER chaperone interactions not characterized
    • Rescue by chemical chaperones not tested
  6. 2012 Medium

    Whether in-frame deletions could selectively impair anticoagulant activity while sparing catalytic function was tested; the c.574_576del variant retained near-normal amidolytic activity but only 43.6% anticoagulant activity, demonstrating a dissociation between substrate hydrolysis and macromolecular substrate (FVa/FVIIIa) recognition.

    Evidence In vitro expression with both amidolytic (chromogenic) and anticoagulant (clotting-based) functional assays

    PMID:22817391

    Open questions at the time
    • Binding affinity for factor Va or VIIIa not directly measured
    • Structural basis for selective loss of anticoagulant activity not resolved
    • Thrombomodulin-dependent activation kinetics not assessed
  7. 2022 Medium

    Building on earlier secretion-defect findings, the Gly86Asp variant confirmed that type I deficiency can arise from impaired secretion without altered transcription, with multiple orthogonal methods (qRT-PCR, ELISA, Western blot) distinguishing transcriptional from post-translational mechanisms.

    Evidence qRT-PCR, ELISA of supernatant and lysate, Western blot in HEK 293FT cells

    PMID:35810421

    Open questions at the time
    • Glycosylation status and folding intermediates not examined
    • Single cell line used
    • Endogenous hepatocyte expression not studied
  8. 2024 Medium

    The question of how missense mutations affect enzyme kinetics was quantitatively addressed; N355S, G392E, and T314A variants showed increased Km and decreased Vmax, directly demonstrating impaired substrate binding and catalysis as mechanisms of type II deficiency, with T314A additionally reducing secretion.

    Evidence Enzyme kinetics assays (Km/Vmax determination), ELISA, Western blot, and PyMOL structural modelling in HEK293 cells

    PMID:39743273

    Open questions at the time
    • Natural substrates (FVa, FVIIIa) not used as kinetic substrates
    • No thrombin generation or coagulation-based functional validation
    • Structural predictions not validated by experimental structure determination
  9. 2025 High

    Deep intronic variants had been largely uncharacterized; four deep intronic substitutions were shown by minigene assays to cause pathogenic splicing defects (intron retention, pseudo-exon activation), expanding the mutational spectrum of PROC deficiency beyond coding and canonical splice sites.

    Evidence Whole PROC gene NGS; minigene splicing assays in HeLa and Huh7 cells; SpliceAI and MaxEntScan in silico prediction

    PMID:40789311

    Open questions at the time
    • Endogenous hepatocyte splicing patterns not confirmed
    • Quantitative contribution of aberrant isoforms to plasma protein C levels unknown
    • NMD susceptibility of aberrant transcripts not directly tested
  10. 2026 High

    Whether splice-site mutations in PROC could be therapeutically corrected at the RNA level was unknown; engineered U1 and U7 snRNAs partially rescued normal splicing for multiple splice-site variants in minigene assays, establishing proof-of-concept for splice-directed RNA therapy of protein C deficiency.

    Evidence Minigene splicing assays with U1/U7 snRNA co-transfection in HeLa and Huh7 cells; protein expression and activity validation

    PMID:41791661

    Open questions at the time
    • In vivo delivery and efficacy not demonstrated
    • Rescue was partial; degree of clinical benefit unpredictable
    • Off-target splicing effects of engineered snRNAs not assessed
  11. 2026 Medium

    The functional consequence of protein C deficiency on thrombin generation in hemophilia A was quantitatively established; reduced protein C concentration increased thrombin generation in FVIII-deficient plasma upon thrombomodulin addition, demonstrating that PC deficiency can attenuate bleeding phenotype by improving thrombin generation.

    Evidence Recombinant PROC expression in Expi293F cells; chromogenic activity assay; thrombin generation assay in FVIII-deficient plasma with varying PC concentrations

    PMID:41791668

    Open questions at the time
    • In vivo confirmation of bleeding attenuation in hemophilia A patients with PC deficiency not established
    • Dose-response relationship between PC levels and clinical phenotype not defined
    • Interaction with other natural anticoagulants (protein S, antithrombin) not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for selective anticoagulant vs. amidolytic defects, the ER quality-control pathway responsible for retention/degradation of misfolded protein C variants, and whether splice-directed RNA therapeutics can restore clinically meaningful protein C levels in vivo.
  • No high-resolution structures of disease-causing mutant protein C forms
  • ER chaperone and degradation pathway specificity unknown
  • In vivo efficacy of U1/U7 snRNA splice correction not tested
  • Contribution of deep intronic variants to unexplained protein C deficiency in clinical cohorts not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005576 extracellular region 5
Pathway
R-HSA-109582 Hemostasis 3

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 The PROC c.574_576del in-frame deletion variant produces a protein C with markedly reduced anticoagulant activity (43.6% of wild-type) while retaining near-normal amidolytic activity, demonstrating a type II (functional) defect. In vitro expression studies established that the anticoagulant defect is intrinsic to the mutant protein. In vitro expression in cell lines, functional amidolytic and anticoagulant activity assays Journal of thrombosis and haemostasis : JTH Medium 22817391
2000 An intronic regulatory element located >500 bp downstream of the core promoter within intron 1 of the human PROC gene enhances promoter-driven expression in human hepatoma cells. A 142 bp sequence within this element is required for high-level expression; a duplicate copy of this element is also present upstream. Transcription factor HNF-1 represses (rather than activates) the promoter when coupled to the intronic sequence. Transient transfection of PROC promoter-luciferase reporter constructs in human hepatoma cells; conventional alignment and complexity analysis to identify conserved regions Human genetics Medium 11140943
1995 Polymorphic haplotypes in the human PROC gene promoter (T/A vs C/G at two linked diallelic sites) differentially drive transcription: the T/A haplotype exhibits at least 2-fold higher transcription efficiency than the C/G haplotype in HepG2 hepatoma cells. Transient transfection of PROC promoter-luciferase reporter constructs in HepG2 cells Blood coagulation & fibrinolysis Medium 7548679
1996 Nonsense mutations, frameshift deletions, and splice-site mutations in the PROC gene are frequently subject to allelic exclusion at the mRNA level (NMD-like mechanism), with only normal-allele-derived mRNA detected by RT-PCR/sequencing; one 2-bp insertion instead generated a cryptic splice site producing an aberrant mRNA with a premature stop codon rather than allelic exclusion. RT-PCR and direct sequencing of ectopic PROC transcripts from patient lymphocytes; polymorphism analysis to confirm allele-specific exclusion Thrombosis and haemostasis Medium 8822578
2002 The D180G missense mutation in the protease domain of protein C causes a severe reduction in secretion (79% decrease vs wild-type) without altering intracellular protein content, consistent with protein misfolding and intracellular retention/degradation. Structural modelling of the X-ray structure of activated protein C predicted local destabilisation by the mutation. Transient expression of PROC mutant in HK-293 cells with ELISA of culture media and cell lysates; computational structural analysis using X-ray structure of activated protein C Thrombosis and haemostasis Medium 12362235
2019 The PROC p.Ala178Pro missense variant causes type I protein C deficiency by reducing secretion of the protein C antigen from cells, as demonstrated by in vitro cell studies showing consistently reduced PROC antigen concentration in media from mutant-transfected cells relative to controls. In vitro cell line expression with PROC antigen measurement in conditioned media; clinical plasma protein C activity measurement in variant carriers Journal of cellular and molecular medicine Medium 31338992
2024 The PROC p.Gly334Ser missense variant significantly decreases protein C secretion into culture media from HEK293T cells (but not from Huh-7 cells), without reducing intracellular protein C levels, indicating impaired secretion as the pathogenic mechanism. Western blot confirmed expression levels in cell lysates were not significantly altered. Transfection of PROC expression vectors into Huh-7 and HEK293T cells; Western blot of cell lysates and conditioned media American heart journal plus : cardiology research and practice Medium 40008275
2022 The PROC p.Gly86Asp variant impairs secretion of protein C without altering mRNA transcription levels: mutant PC antigen was 81.3% of wild-type in culture supernatant but 110% in cell lysate, indicating intracellular retention as the molecular mechanism of type I PC deficiency. qRT-PCR for mRNA level; ELISA for PC antigen in supernatant and lysate; Western blot for protein level in HEK 293FT cells transfected with wild-type or mutant PROC Zhonghua yi xue yi chuan xue za zhi Medium 35810421
2024 PROC missense mutations N355S, G392E, and T314A cause functional defects in protein C by reducing substrate binding affinity (increased Km) and catalytic rate (decreased Vmax) in enzyme kinetics assays; T314A additionally reduces secretion. Structural modelling showed spatial collisions introduced by substitutions distort the active site region. Transient transfection of HEK293 cells; real-time PCR for mRNA; ELISA and Western blot for protein levels; enzyme kinetics (Km, Vmax) assay; PyMOL structural modelling Zhongguo shi yan xue ye xue za zhi Medium 39743273
2026 The PROC p.Trp414Arg variant causes near-complete loss of protein C activity (0% vs 90% for wild-type) and nearly absent secretion (4% vs 100%) when expressed in Expi293F cells, confirming a quantitative (type I) protein C deficiency. Thrombin generation assays in FVIII-deficient plasma showed that reduced protein C concentrations increase thrombin generation upon thrombomodulin addition, demonstrating that PC deficiency attenuates bleeding in hemophilia A by improving thrombin generation. Recombinant protein production in Expi293F cells; chromogenic activity assay; competitive ELISA for protein quantity; thrombin generation assays in factor VIII-deficient plasma with varying PC concentrations; AlphaFold 3 structural prediction Journal of thrombosis and haemostasis : JTH Medium 41791668
2026 Multiple PROC variants at exon-intron boundaries induce complex splicing defects (exon skipping, cryptic donor site activation, multiple aberrant isoforms). Engineered U1 and U7 snRNAs partially restore normal splicing in affected variants, demonstrating feasibility of splice-directed RNA therapeutic correction of PROC splice-site mutations. Minigene splicing assays in HeLa and Huh7 cells; engineered U1/U7 snRNA rescue experiments; in silico splice prediction (SpliceAI and four other tools); protein expression, secretion, and activity analyses Journal of thrombosis and haemostasis : JTH High 41791661
2025 Deep intronic PROC substitutions (c.237+75G>A, c.535+936C>T, c.536-95G>A, c.796+49G>T) cause pathogenic splicing defects including intron retention in mature mRNA or pseudo-exon activation, identified by in vitro splicing assays in HeLa and Huh7 cells; a 541 bp deletion and a 1.298 kb balanced inversion also disrupt the PROC gene and are classified as pathogenic. Whole PROC gene NGS; in vitro minigene splicing assay in HeLa and Huh7 cells; in silico analysis (MaxEntScan and SpliceAI) Thrombosis and haemostasis High 40789311
1993 A Gla domain missense mutation Arg15→Trp (CGG→TGG) in the PROC gene causes type II protein C deficiency (reduced anticoagulant function with preserved antigen), implicating the conserved pentapeptide in the Gla domain in functional calcium-dependent membrane binding of protein C. DNA sequencing; family co-segregation analysis; phenotypic classification (antigen vs. functional activity) Blood coagulation & fibrinolysis Low 8499568
1991 Aerobic exercise activates the PROC/PAR1/Nrf2/HO-1 signaling pathway in a rat model of diabetic cardiomyopathy, where protein C (encoded by PROC) was reduced in DCM hearts and restored by exercise; Western blotting confirmed pathway activation, suggesting protein C signals through PAR1 to activate Nrf2/HO-1 antioxidant defense. Rat diabetic cardiomyopathy model; Western blotting for pathway components; bioinformatics gene expression analysis Frontiers in physiology Low 41695095

Source papers

Stage 0 corpus · 99 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 PROC c.574_576del polymorphism: a common genetic risk factor for venous thrombosis in the Chinese population. Journal of thrombosis and haemostasis : JTH 53 22817391
1981 Use of bacteriophage transposon Mu d1 to determine the orientation for three proC-linked phosphate-starvation-inducible (psi) genes in Escherichia coli K-12. Journal of bacteriology 52 6260750
2008 PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study. Journal of thrombosis and haemostasis : JTH 49 18680534
1997 ProC Global: the first functional screening assay for the complete protein C pathway. Clinical chemistry 47 9299966
1992 Molecular cloning and evidence for osmoregulation of the delta 1-pyrroline-5-carboxylate reductase (proC) gene in pea (Pisum sativum L.). Plant physiology 29 11537868
2000 Screening for abnormalities of the protein C anticoagulant pathway using the ProC Global assay. Results of a European multicenter evaluation. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 28 10937806
1990 Comparison of proC and other housekeeping genes of Pseudomonas aeruginosa with their counterparts in Escherichia coli. Gene 28 2107123
2004 R147W mutation of PROC gene is common in venous thrombotic patients in Taiwanese Chinese. American journal of hematology 27 15114590
1988 Assignment of the human protein C gene (PROC) to chromosome region 2q14----q21 by in situ hybridization. Cytogenetics and cell genetics 26 3356168
1992 A novel homozygous missense mutation in the protein C (PROC) gene causing recurrent venous thrombosis. Human genetics 25 1511988
1990 Complementation of an Escherichia coli proC mutation by a gene cloned from Treponema pallidum. Journal of bacteriology 25 2188947
2005 Auxotrophic markers pyrF and proC can replace antibiotic markers on protein production plasmids in high-cell-density Pseudomonas fluorescens fermentation. Biotechnology progress 23 15801769
1994 A homozygous deletion/insertion mutation in the protein C (PROC) gene causing neonatal Purpura fulminans: prenatal diagnosis in an at-risk pregnancy. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 23 7841323
1997 Evaluation of a new screening assay ProC Global for identification of defects in the protein C/protein S anticoagulant pathway. Thrombosis research 22 9330432
1994 Molecular cloning and sequence analysis of the proC gene encoding delta 1-pyrroline-5-carboxylate reductase from an extremely thermophilic eubacterium Thermus thermophilus. Biochemical and biophysical research communications 21 8123043
2000 Identification of an intronic regulatory element in the human protein C (PROC) gene. Human genetics 20 11140943
1999 Proline biosynthesis from L-ornithine in Clostridium sticklandii: purification of delta1-pyrroline-5-carboxylate reductase, and sequence and expression of the encoding gene, proC. Microbiology (Reading, England) 19 10220161
2005 "ProC Global": a functional screening test that predicts recurrent venous thromboembolism. Thrombosis and haemostasis 17 15735816
2020 Recurrent PROC and novel PROS1 mutations in Vietnamese patients diagnosed with idiopathic deep venous thrombosis. International journal of laboratory hematology 15 32964666
2001 Sensitivity of the ProC global assay for protein C pathway abnormalities. clinical experience in 899 unselected patients with venous thromboembolism. Thrombosis research 15 11672753
2019 Burden of rare exome sequence variants in PROC gene is associated with venous thromboembolism: a population-based study. Journal of thrombosis and haemostasis : JTH 13 31680443
2017 R147W in PROC Gene Is a Risk Factor of Thromboembolism in Thai Children. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 13 28511552
1995 Polymorphic variation in the human protein C (PROC) gene promoter can influence transcriptional efficiency in vitro. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 13 7548679
1988 Transcriptional regulation of the proC gene of Salmonella typhimurium. Journal of bacteriology 13 3129409
2003 Familial thrombophilia is an oligogenetic disease: involvement of the prothrombin G20210A, PROC and PROS gene mutations. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 12 12632031
1996 Homozygosity for R87H missense mutation and for a rare intron 7 DNA variant (7054G --> A) in the PROC genes of three siblings initially classified as heterozygotes for protein C deficiency. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 12 8845458
2019 Pathogenic variants of PROC gene caused type I activity deficiency in a familial Chinese venous thrombosis. Journal of cellular and molecular medicine 11 31338992
2011 Proteolysis of the class II-associated invariant chain generates a peptide binding site in intracellular HLA-DR molecules. Proc. Natl. Acad. Sci. USA. 1991. 88: 3150-3154. Journal of immunology (Baltimore, Md. : 1950) 11 21772034
2007 Prediction of recurrent venous thromboembolism by measuring ProC Global. Thrombosis and haemostasis 11 18064319
2006 Evaluation of ProC Global assay in women with a history of venous thromboembolism on hormonal therapy. Thrombosis and haemostasis 11 17080213
2001 The reduced sensitivity of the ProC Global test in protein S deficient subjects reflects a reduction in the associated thrombotic risk. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 11 11734670
2000 The Bradyrhizobium japonicum proline biosynthesis gene proC is essential for symbiosis. Applied and environmental microbiology 11 11097929
1998 Comparative gene mapping: cytogenetic localization of PROC, EN1, ALPI, TNP1, and IL1B in cattle and sheep reveals a conserved rearrangement relative to the human genome. Cytogenetics and cell genetics 11 9925918
1992 Two different missense mutations at Arg 178 of the protein C (PROC) gene causing recurrent venous thrombosis. Human genetics 10 1511989
2018 Polymorphisms of F2, PROC, PROZ, and F13A1 Genes are Associated With Recurrent Spontaneous Abortion in Chinese Han Women. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 9 29363996
2008 Estimating relative risks for common outcome using PROC NLP. Computer methods and programs in biomedicine 9 18291556
1996 Ectopic transcript analysis indicates that allelic exclusion is an important cause of type I protein C deficiency in patients with nonsense and frameshift mutations in the PROC gene. Thrombosis and haemostasis 9 8822578
2001 Modification of the ProC Global assay using dilution of patient plasma in factor V-depleted plasma as a screening assay for factor V Leiden mutation. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 8 11685046
1993 A Gla domain mutation (Arg 15-->Trp) in the protein C (PROC) gene causing type 2 protein C deficiency and recurrent venous thrombosis. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 8 8499568
2017 Protein C Deficiency Caused by a Novel Mutation in the PROC Gene in an Infant with Delayed Onset Purpura Fulminans. Case reports in dermatological medicine 7 29082047
2012 Novel association of a PROC variant with ischemic stroke in a Chinese Han population. Human genetics 7 22976599
2007 An abnormal ProC Global test result is associated with an increased risk of venous thromboembolism independent of test sensitivity for protein C pathway abnormalities. Thrombosis and haemostasis 7 17598017
2002 ProC Global assay in the evaluation of women with history of severe preeclampsia or HELLP syndrome. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 7 12518722
1995 Severe type I protein C deficiency in a compound heterozygote for Y124C and Q132X mutations in exon 6 of the PROC gene. Thrombosis and haemostasis 7 8607097
1993 A novel nonsense mutation in the protein C (PROC) gene (Trp-29-->term) causing recurrent venous thrombosis. Human genetics 7 8462980
2018 Slow Elevation in Protein C Activity without a PROC Mutation in a Neonate with Intracranial Hemorrhage. AJP reports 6 29657898
2015 Thrombin generation, ProC(®)Global, prothrombin time and activated partial thromboplastin time in thawed plasma stored for seven days and after methylene blue/light pathogen inactivation. Blood transfusion = Trasfusione del sangue 6 26192785
2009 Effectiveness of argon plasma coagulation in the treatment of chronic actinic proc. Revista espanola de enfermedades digestivas 6 19335044
2002 Protein C deficiency caused by homozygosity for a novel PROC D180G mutation--in vitro expression and structural analysis of the mutation. Thrombosis and haemostasis 6 12362235
2023 Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study. Thrombosis journal 5 37789321
2019 Protein C deficiency; PROC gene variants in a Danish population. Thrombosis research 5 31821907
2017 ProC-TEL: Profiling of Protein C-Termini by Enzymatic Labeling. Methods in molecular biology (Clifton, N.J.) 5 28315248
2015 Childhood asthma is associated with polymorphic markers of PROC on 2q14 in addition to 17q21 locus. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 5 25643747
2013 A novel mutation in protein C gene (PROC) causing severe phenotype in neonatal period. Pediatric blood & cancer 5 24115609
2022 A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms. Genes 4 35627118
2020 Severe Protein C Deficiency due to Novel Biallelic Variants in PROC and Their Phenotype Correlation. Acta haematologica 4 32980846
2019 Analysis of PROC and PROS1 single nucleotide polymorphisms in a thrombophilia family. The clinical respiratory journal 4 31295762
2017 Protein C deficiency resulting from two mutations in PROC presenting with recurrent venous thromboembolism. Journal of vascular surgery cases and innovative techniques 4 29349439
2010 Multicopy proC in Streptomyces coelicolor A3(2) elicits a transient production of prodiginines, while proC deletion does not yield a proline auxotroph. Journal of molecular microbiology and biotechnology 4 20924202
2004 Inroads into base excision repair II. The discovery of DNA glycosylases. "An N-glycosidase from Escherichia coli that releases free uracil from DNA containing deaminated cytosine residues," Proc. Nat. Acad. Sci. USA, 1974. DNA repair 4 15380109
2024 The adc1 knockout with proC overexpression in Synechocystis sp. PCC 6803 induces a diversion of acetyl-CoA to produce more polyhydroxybutyrate. Biotechnology for biofuels and bioproducts 3 38218963
2022 Compound heterozygous protein C deficiency with pulmonary embolism caused by a novel PROC gene mutation: Case report and literature review. Medicine 3 36281079
2021 Pathogenic variants of PROC gene caused type II activity deficiency in a Chinese family: A case report. Medicine 3 33761690
2021 Severe protein C deficiency in a newborn caused by a homozygous pathogenic variant in the PROC gene: a case report. BMC pediatrics 3 34654403
2016 Genetic association of PROC variants with pulmonary embolism in Northern Chinese Han population. SpringerPlus 3 27026844
2013 A novel mutation c.1048A>T at codon 350(Lys>Stop) in PROC gene causing neonatal purpura fulminans. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 3 24158118
1995 Three novel mutations in the protein C (PROC) gene causing venous thrombosis. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 3 7605880
2025 A phase 1b, multicentre, dose escalation, safety and pharmacokinetics study of tilvestamab (BGB149) in relapsed, platinum-resistant, high-grade serous ovarian cancer (PROC) patients. British journal of cancer 2 40696160
2024 Protein C deficiency with recurrent systemic thrombosis associated with compound heterozygous PROC missense variants. American heart journal plus : cardiology research and practice 2 40008275
2020 [Phenotypic and genotypic analysis of a pedigree affected with hereditary protein C deficiency due to heterozygous deletional mutation of PROC gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2 32924112
2001 A novel silent substitution (C8516T) in exon 9 of the human PROC gene. Yonsei medical journal 2 11456407
2001 ProC global: a new automated screening assay for the evaluation of total function of the protein C system. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 2 11697723
2025 Novel insights into inherited protein C deficiency from an interactive PROC variant database. Journal of thrombosis and haemostasis : JTH 1 40803570
2023 Analysis of PROC mutations and clinical features in 22 unrelated families with inherited protein C deficiency. Annals of hematology 1 37950050
2023 The c.1243T>C mutation in the PROC gene is linked with inherited protein C deficiency and severe purpura fulminans. Clinical case reports 1 38046799
2022 [Analysis of PROC gene variant in a Chinese pedigree affected with hereditary protein C deficiency]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 36317209
2021 The neonatal PROC gene rs1799809 polymorphism modifies the association between prenatal air pollutants exposure and PROC promoter methylation. Environmental science and pollution research international 1 34617212
2020 An Embolic Stroke in a Patient With PROC p.Lys193del. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 1 32057655
2020 PROC Promoter Single Nucleotide Polymorphisms Associated With Low Protein C Activity But Not Increased Risk of Thromboembolism in Pediatric Population. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 1 32609543
2012 Acroangiodermatitis of Mali in protein C deficiency due to a novel PROC gene mutation. The American Journal of dermatopathology 1 22441373
2011 Evaluation of Pro-C global for identification of defects in protein C/S anticoagulant pathway. Journal of Ayub Medical College, Abbottabad : JAMC 1 22830156
1998 Three novel PROC gene lesions causing protein C deficiency. Clinical genetics 1 9788727
2026 The Substrate Versatility of Δ1-Pyrroline-5-carboxylate Reductase (ProC) from Escherichia coli. Molecules (Basel, Switzerland) 0 41683478
2026 Aerobic exercise inhibits oxidative stress and improves diabetic cardiomyopathy in rats by activating the PROC/PAR1/Nrf2/HO-1 signaling pathway. Frontiers in physiology 0 41695095
2026 Functional impact of PROC variants on splicing and protein C activity: evidence for clinical reclassification and RNA therapeutic approaches. Journal of thrombosis and haemostasis : JTH 0 41791661
2026 Prothrombotic PROC variant rebalancing hemostasis in severe hemophilia A with attenuated bleeding risk. Journal of thrombosis and haemostasis : JTH 0 41791668
2025 Novel Association of Thrombophilic PROS1, PROC and CPB2 Genes Polymorphisms with Recurrent Spontaneous Miscarriage Women in Jordan. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 0 40232193
2025 Whole PROC Gene Sequencing to Explain Genetically Unresolved Protein C Deficiencies. Thrombosis and haemostasis 0 40789311
2025 Multi-omics evidence supports PROC as a potential predictor of VTE risk: A Mendelian randomization study. Medicine 0 41239582
2025 A pedigree analysis of deep venous thrombosis caused by rare compound heterozygous PROC mutations combined with a heterozygous THBD mutation. Thrombosis journal 0 41454398
2024 Digenic Inheritance of PROC and SERPINC1 Mutations Contributes to Multiple Sites Venous Thrombosis. Hamostaseologie 0 38224959
2024 Two cases of venous thromboembolism in siblings after splenectomy due to a novel PROC gene mutation. Thrombosis journal 0 38504286
2024 Successful ECMO treatment in patients with cerebral hemorrhage and PROC gene mutation associated with VTE: a case report. Thrombosis journal 0 38609929
2024 [Molecular Mechanism of Protein C Deficiency Caused by Mutations of PROC Gene N355S, G392E, T314A]. Zhongguo shi yan xue ye xue za zhi 0 39743273
2023 [Clinical and genetic analysis of a rare fetus with Protein C deficiency due to compound heterozygous variants of PROC gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 37906136
2022 [Analysis of the molecular pathogenesis of hereditary protein C deficiency due to a p.Gly86Asp variant of the PROC gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 35810421
2021 [Genetic and Clinical Characteristics of A Family with Combined PROC and PROS1 Genetic Variants]. Zhongguo shi yan xue ye xue za zhi 0 33812436
2019 A Novel Frameshift Homozygous Mutation in DHCR7 with a Known Missense Homozygous Mutation in the PROC in a 6-Year-Old Boy: A Child with Two Rare Genetic Diseases. Journal of pediatric genetics 0 31406626
2010 [Polymorphic markers G(-455)A of gene FGB and C(-1654)T of gene PROC and genetic predisposition to unfavorable outcomes patients undergoing acute coronary syndrome]. Molekuliarnaia biologiia 0 20873219