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THPH3
MCID: THR067
MIFTS: 27

Thrombophilia Due to Protein C Deficiency, Autosomal Dominant (THPH3)

Categories: Blood diseases, Genetic diseases
Genes Variations Tissues Publications Symptoms & Phenotypes
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Aliases & Classifications for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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MalaCards integrated aliases for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant:

Name: Thrombophilia Due to Protein C Deficiency, Autosomal Dominant 57 74 13
Thph3 57 74
Thrombophilia, Hereditary, Due to Protein C Deficiency, Autosomal Dominant 72
Protein C Deficiency, Autosomal Dominant 57
Protein C Deficiency Autosomal Dominant 74
Proc Deficiency, Autosomal Dominant 57
Proc Deficiency Autosomal Dominant 74

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
vast majority of heterozygotes are asymptomatic
protein c deficiency is found in 3-4% of patients with venous thromboembolism
acquired protein c deficiency seen in liver disease, dic, and following surgery
see also autosomal recessive form ()


HPO:

32
thrombophilia due to protein c deficiency, autosomal dominant:
Inheritance autosomal dominant inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases
Anatomical: Blood diseases
See all MalaCards categories (disease lists)


External Ids:

UMLS 72 C2674321
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Summaries for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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OMIM : 57 Heterozygous protein C deficiency is characterized by recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic (Millar et al., 2000). Individuals with decreased amounts of protein C are classically referred to as having type I deficiency and those with normal amounts of a functionally defective protein as having type II deficiency (Bertina et al., 1984). Acquired protein C deficiency is a clinically similar disorder caused by development of an antibody against protein C. Clouse and Comp (1986) reviewed the structural and functional properties of protein C and discussed both hereditary and acquired deficiency of protein C. (176860)

MalaCards based summary : Thrombophilia Due to Protein C Deficiency, Autosomal Dominant, is also known as thph3. An important gene associated with Thrombophilia Due to Protein C Deficiency, Autosomal Dominant is PROC (Protein C, Inactivator Of Coagulation Factors Va And VIIIa). Affiliated tissues include skin, liver and eye, and related phenotypes are abnormality of the eye and hypercoagulability

UniProtKB/Swiss-Prot : 74 Thrombophilia due to protein C deficiency, autosomal dominant: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency.

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Related Diseases for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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Symptoms & Phenotypes for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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Human phenotypes related to Thrombophilia Due to Protein C Deficiency, Autosomal Dominant:

32 (show all 9)
# Description HPO Frequency HPO Source Accession
1 abnormality of the eye 32 HP:0000478
2 hypercoagulability 32 HP:0100724
3 pulmonary embolism 32 HP:0002204
4 abnormality of the nervous system 32 HP:0000707
5 deep venous thrombosis 32 HP:0002625
6 warfarin-induced skin necrosis 32 HP:0001038
7 superficial thrombophlebitis 32 HP:0002638
8 cerebral venous thrombosis 32 HP:0005305
9 reduced protein c activity 32 HP:0005543

Symptoms via clinical synopsis from OMIM:

57
Respiratory Lung:
pulmonary embolism

Skin Nails Hair Skin:
warfarin-induced skin necrosis

Laboratory Abnormalities:
plasma protein c deficiency

Cardiovascular Vascular:
deep venous thrombosis
superficial thrombophlebitis

Neurologic Central Nervous System:
cerebral thrombosis (e.g. protein c deficiency)

Clinical features from OMIM:

176860
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Drugs & Therapeutics for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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Search Clinical Trials , NIH Clinical Center for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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Genetic Tests for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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Anatomical Context for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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MalaCards organs/tissues related to Thrombophilia Due to Protein C Deficiency, Autosomal Dominant:

41
Skin, Liver, Eye
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Publications for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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Articles related to Thrombophilia Due to Protein C Deficiency, Autosomal Dominant:

(show all 48)
# Title Authors PMID Year
1
Molecular genetic analysis of severe protein C deficiency. 8 71
10942114 2000
2
Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect. 8 71
8093743 1993
3
Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene. 8 71
2437584 1987
4
Mice with a severe deficiency in protein C display prothrombotic and proinflammatory phenotypes and compromised maternal reproductive capabilities. 8
15902301 2005
5
Symptomatic type 1 protein C deficiency caused by a de novo Ser270Leu mutation in the catalytic domain. 71
11380450 2001
6
Protein C deficiency related to valproic acid therapy: a possible association with childhood stroke. 8
11060540 2000
7
An unknown genetic defect increases venous thrombosis risk, through interaction with protein C deficiency. 71
9683579 1998
8
Type I protein C deficiency caused by disruption of a hepatocyte nuclear factor (HNF)-6/HNF-1 binding site in the human protein C gene promoter. 71
9553065 1998
9
Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly. 8
9577282 1998
10
Protein C Nagoya, an elongated mutant of protein C, is retained within the endoplasmic reticulum and is associated with GRP78 and GRP94. 71
8639775 1996
11
Protein C deficiency: summary of the 1995 database update. 8
8594568 1996
12
Recurrence of the PROC gene mutation R178Q: independent origins in Spanish protein C deficiency patients. 71
8807339 1996
13
Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. The French Network on the behalf of INSERM. 8
7795227 1995
14
Population differences in the frequency of the factor V Leiden variant among people with clinically symptomatic protein C deficiency. 8
7562967 1995
15
Protein C deficiency: a database of mutations, 1995 update. On behalf of the Subcommittee on Plasma Coagulation Inhibitors of the Scientific and Standardization Committee of the ISTH. 8
7482420 1995
16
Disruption of a binding site for hepatocyte nuclear factor 1 in the protein C gene promoter is associated with hereditary thrombophilia. 71
7881411 1994
17
Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. 8
8049422 1994
18
Protein C and S deficiency, thrombophilia, and hypofibrinolysis: pathophysiologic causes of Legg-Perthes disease. 8
8047373 1994
19
Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis. 71
8400292 1993
20
A novel point mutation (Val 297-->Met) in the serine proteinase domain of protein C in a patient with both venous and arterial thromboembolic disease. 71
8218861 1993
21
Dysfunctional protein C deficiency (type II). A report of 11 cases in 3 American families and review of the literature. 8
8322701 1993
22
Protein C deficiency: a database of mutations. For the Protein C & S Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. 8
8446940 1993
23
Impaired secretion of the elongated mutant of protein C (protein C-Nagoya). Molecular and cellular basis for hereditary protein C deficiency. 71
1469096 1992
24
A novel homozygous missense mutation in the protein C (PROC) gene causing recurrent venous thrombosis. 71
1511988 1992
25
Two different missense mutations at Arg 178 of the protein C (PROC) gene causing recurrent venous thrombosis. 71
1511989 1992
26
Protein C deficiency: identification of a novel two-base pair insertion and two point mutations in exon 7 of the protein C gene in Spanish families. 71
1301954 1992
27
The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I: heterogeneity and founder effects. 71
1868249 1991
28
A new hereditary abnormal protein C (protein C Yonago) with a dysfunctional Gla-domain. 8
1771629 1991
29
Protein C London 1: recurrent mutation at Arg 169 (CGG----TGG) in the protein C gene causing thrombosis. 71
2602169 1989
30
The clinical spectrum of heterozygous protein C deficiency in a large New England kindred. 8
2521802 1989
31
Familial type II protein C deficiency associated with warfarin-induced skin necrosis and bilateral adrenal hemorrhage. 8
3189320 1988
32
A thrombotic state due to an abnormal protein C. 71
3185623 1988
33
A fatal thrombotic disorder associated with an acquired inhibitor of protein C. 8
3683503 1987
34
Childhood stroke associated with protein C or S deficiency. 8
2958610 1987
35
Mapping through somatic cell hybrids and cDNA probes of protein C to chromosome 2, factor X to chromosome 13, and alpha 1-acid glycoprotein to chromosome 9. 8
3463531 1986
36
Coumarin induced acral skin necrosis associated with hereditary protein C deficiency. 8
3755068 1986
37
The regulation of hemostasis: the protein C system. 8
3010107 1986
38
Prenatal diagnosis of hereditary protein C deficiency. 8
3840865 1985
39
Protein C deficiency in Austria. 8
3840917 1985
40
Congenital protein C deficiency and thrombotic disease in nine French families. 8
6437521 1984
41
Hereditary dysfunctional protein C (protein C Bergamo) and thrombosis. 8
6148564 1984
42
Characterization of a cDNA coding for human protein C. 71
6589623 1984
43
The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency. 8
6547008 1984
44
Protein C deficiency in two Austrian families. 8
6665761 1983
45
Congenital protein C deficiency and venous thromboembolism. A study of three Dutch families. 8
6688122 1983
46
Protein C deficiency in a Dutch family with thrombotic disease. 8
6897135 1982
47
Deficiencies of protein C, an inhibitor of blood coagulation. 8
6125639 1982
48
Deficiency of protein C in congenital thrombotic disease. 8
6895379 1981
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Variations for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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ClinVar genetic disease variations for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant:

6 (show top 50) (show all 82)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PROC NM_000312.3(PROC): c.340G> T (p.Gly114Cys) single nucleotide variant Pathogenic rs374476971 2:128180687-128180687 2:127423111-127423111
2 PROC NM_000312.3(PROC): c.1201G> A (p.Asp401Asn) single nucleotide variant Pathogenic rs142742242 2:128186337-128186337 2:127428761-127428761
3 PROC NM_000312.3(PROC): c.446A> C (p.His149Pro) single nucleotide variant Pathogenic rs121918159 2:128180895-128180895 2:127423319-127423319
4 PROC PROC, -14T-C single nucleotide variant Pathogenic
5 PROC NM_000312.3(PROC): c.1015G> A (p.Val339Met) single nucleotide variant Pathogenic rs121918158 2:128186151-128186151 2:127428575-127428575
6 PROC NM_000312.3(PROC): c.678G> C (p.Gln226His) single nucleotide variant Pathogenic rs121918155 2:128183803-128183803 2:127426227-127426227
7 PROC NM_000312.3(PROC): c.678+9C> T single nucleotide variant Pathogenic 2:128183812-128183812 2:127426236-127426236
8 PROC NM_000312.3(PROC): c.552_553insTT (p.Arg185fs) insertion Pathogenic 2:128183677-128183678 2:127426101-127426102
9 PROC NM_000312.3(PROC): c.814C> T (p.Arg272Cys) single nucleotide variant Pathogenic rs121918154 2:128185950-128185950 2:127428374-127428374
10 PROC PROC, 1-BP DEL, 8857G deletion Pathogenic
11 PROC NM_000312.3(PROC): c.659G> A (p.Arg220Gln) single nucleotide variant Pathogenic rs121918153 2:128183784-128183784 2:127426208-127426208
12 PROC NM_000312.3(PROC): c.658C> T (p.Arg220Trp) single nucleotide variant Pathogenic rs121918152 2:128183783-128183783 2:127426207-127426207
13 PROC NM_000312.3(PROC): c.1000G> A (p.Gly334Ser) single nucleotide variant Pathogenic rs121918150 2:128186136-128186136 2:127428560-127428560
14 PROC NM_000312.3(PROC): c.925G> A (p.Ala309Thr) single nucleotide variant Pathogenic rs121918146 2:128186061-128186061 2:127428485-127428485
15 PROC NM_000312.3(PROC): c.1332G> C (p.Trp444Cys) single nucleotide variant Pathogenic rs121918142 2:128186468-128186468 2:127428892-127428892
16 PROC NM_000312.3(PROC): c.1042C> T (p.Arg348Ter) single nucleotide variant Pathogenic rs121918141 2:128186178-128186178 2:127428602-127428602
17 PROC NM_000312.3(PROC): c.889G> C (p.Asp297His) single nucleotide variant Pathogenic 2:128186025-128186025 2:127428449-127428449
18 PROC NM_000312.3(PROC): c.400+1G> A single nucleotide variant Pathogenic 2:128180748-128180748 2:127423172-127423172
19 PROC NM_000312.3(PROC): c.169C> T (p.Arg57Trp) single nucleotide variant Pathogenic/Likely pathogenic rs757583846 2:128178957-128178957 2:127421381-127421381
20 PROC NM_000312.3(PROC): c.631C> T (p.Arg211Trp) single nucleotide variant Pathogenic/Likely pathogenic rs121918143 2:128183756-128183756 2:127426180-127426180
21 PROC NM_000312.3(PROC): c.811C> T (p.Arg271Trp) single nucleotide variant Likely pathogenic rs767112991 2:128185947-128185947 2:127428371-127428371
22 PROC NM_000312.3(PROC): c.1212dup (p.Pro405fs) duplication Likely pathogenic rs1333329860 2:128186348-128186348 2:127428772-127428772
23 PROC NM_000312.3(PROC): c.352T> C (p.Phe118Leu) single nucleotide variant Likely pathogenic rs1553424043 2:128180699-128180699 2:127423123-127423123
24 PROC NM_000312.3(PROC): c.238-1G> A single nucleotide variant Likely pathogenic rs1553423955 2:128180492-128180492 2:127422916-127422916
25 PROC NM_000312.3(PROC): c.125G> A (p.Arg42His) single nucleotide variant Likely pathogenic rs369504169 2:128178913-128178913 2:127421337-127421337
26 PROC NM_000312.3(PROC): c.199G> A (p.Glu67Lys) single nucleotide variant Likely pathogenic 2:128178987-128178987 2:127421411-127421411
27 PROC NM_000312.3(PROC): c.1166G> C (p.Gly389Ala) single nucleotide variant Likely pathogenic 2:128186302-128186302 2:127428726-127428726
28 PROC NM_000312.3(PROC): c.1242G> A (p.Trp414Ter) single nucleotide variant Likely pathogenic 2:128186378-128186378 2:127428802-127428802
29 PROC NM_000312.3(PROC): c.935C> T (p.Ser312Leu) single nucleotide variant Likely pathogenic rs121918160 2:128186071-128186071 2:127428495-127428495
30 PROC NM_000312.3(PROC): c.565C> T (p.Arg189Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs146922325 2:128183690-128183690 2:127426114-127426114
31 PROC NM_000312.3(PROC): c.1299C> T (p.Gly433=) single nucleotide variant Conflicting interpretations of pathogenicity rs151319700 2:128186435-128186435 2:127428859-127428859
32 PROC NM_000312.3(PROC): c.574_576AAG[1] (p.Lys193del) short repeat Conflicting interpretations of pathogenicity rs199469469 2:128183702-128183704 2:127426126-127426128
33 PROC NM_000312.3(PROC): c.1043G> A (p.Arg348Gln) single nucleotide variant Uncertain significance rs201827066 2:128186179-128186179 2:127428603-127428603
34 PROC NM_000312.3(PROC): c.91G> A (p.Glu31Lys) single nucleotide variant Uncertain significance rs779710709 2:128178879-128178879 2:127421303-127421303
35 PROC NM_000312.3(PROC): c.286C> T (p.Pro96Ser) single nucleotide variant Uncertain significance rs774908523 2:128180633-128180633 2:127423057-127423057
36 PROC NM_000312.3(PROC): c.580C> T (p.Arg194Cys) single nucleotide variant Uncertain significance rs371071104 2:128183705-128183705 2:127426129-127426129
37 PROC NM_000312.3(PROC): c.1010C> T (p.Thr337Ile) single nucleotide variant Uncertain significance rs369881972 2:128186146-128186146 2:127428570-127428570
38 PROC NM_000312.3(PROC): c.52G> A (p.Gly18Ser) single nucleotide variant Uncertain significance rs146793243 2:128177570-128177570 2:127419994-127419994
39 PROC NM_000312.3(PROC): c.1234G> A (p.Gly412Ser) single nucleotide variant Uncertain significance rs139741458 2:128186370-128186370 2:127428794-127428794
40 PROC NM_000312.3(PROC): c.602C> T (p.Thr201Ile) single nucleotide variant Uncertain significance rs886054847 2:128183727-128183727 2:127426151-127426151
41 PROC NM_000312.3(PROC): c.927C> T (p.Ala309=) single nucleotide variant Uncertain significance rs200731614 2:128186063-128186063 2:127428487-127428487
42 PROC NM_000312.3(PROC): c.1237A> G (p.Thr413Ala) single nucleotide variant Uncertain significance rs572021052 2:128186373-128186373 2:127428797-127428797
43 PROC NM_000312.3(PROC): c.160A> T (p.Ser54Cys) single nucleotide variant Uncertain significance rs376049280 2:128178948-128178948 2:127421372-127421372
44 PROC NM_000312.3(PROC): c.322C> A (p.His108Asn) single nucleotide variant Uncertain significance rs200234655 2:128180669-128180669 2:127423093-127423093
45 PROC NM_000312.3(PROC): c.340G> C (p.Gly114Arg) single nucleotide variant Uncertain significance rs374476971 2:128180687-128180687 2:127423111-127423111
46 PROC NM_000312.3(PROC): c.534A> G (p.Ala178=) single nucleotide variant Uncertain significance rs368367611 2:128180983-128180983 2:127423407-127423407
47 PROC NM_000312.3(PROC): c.596G> A (p.Arg199Gln) single nucleotide variant Uncertain significance rs773327173 2:128183721-128183721 2:127426145-127426145
48 PROC NM_000312.3(PROC): c.799G> A (p.Glu267Lys) single nucleotide variant Uncertain significance rs1553425185 2:128185935-128185935 2:127428359-127428359
49 PROC NM_000312.3(PROC): c.548G> T (p.Cys183Phe) single nucleotide variant Uncertain significance rs1284942525 2:128183673-128183673 2:127426097-127426097
50 PROC NM_000312.3(PROC): c.*146T> C single nucleotide variant Uncertain significance rs140461934 2:128186668-128186668 2:127429092-127429092

UniProtKB/Swiss-Prot genetic disease variations for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant:

74 (show all 28)
# Symbol AA change Variation ID SNP ID
1 PROC p.Arg32Cys VAR_006635
2 PROC p.Arg57Trp VAR_006642 rs757583846
3 PROC p.Glu62Ala VAR_006645 rs121918148
4 PROC p.Val76Met VAR_006646 rs121918149
5 PROC p.Gly114Arg VAR_006651 rs374476971
6 PROC p.Gly145Arg VAR_006656 rs370813536
7 PROC p.Pro210Leu VAR_006664 rs121918145
8 PROC p.Arg211Trp VAR_006665 rs121918143
9 PROC p.Arg220Trp VAR_006668 rs121918152
10 PROC p.Arg220Gln VAR_006669 rs121918153
11 PROC p.Ile243Thr VAR_006671 rs774584131
12 PROC p.Arg272Cys VAR_006677 rs121918154
13 PROC p.Pro321Leu VAR_006687 rs132156626
14 PROC p.Gly324Arg VAR_006688
15 PROC p.Arg328Cys VAR_006689 rs201907715
16 PROC p.Thr340Met VAR_006692 rs766261022
17 PROC p.Pro369Leu VAR_006696 rs121109869
18 PROC p.Gly392Arg VAR_006700 rs756467027
19 PROC p.Asp401Asn VAR_006702 rs142742242
20 PROC p.Gly423Ser VAR_006704
21 PROC p.Cys426Tyr VAR_006705
22 PROC p.Thr436Asn VAR_006707
23 PROC p.Tyr441His VAR_006708 rs753436021
24 PROC p.Trp444Cys VAR_006709 rs121918142
25 PROC p.Arg42Ser VAR_055074 rs774572099
26 PROC p.Ala163Val VAR_073147
27 PROC p.Asp297His VAR_074303 rs199469471
28 PROC p.Val420Leu VAR_074307 rs199469472

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Expression for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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Search GEO for disease gene expression data for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant.
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Pathways for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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GO Terms for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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Sources for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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