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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 56 73 13
Thph3 56 73
Thrombophilia, Hereditary, Due to Protein C Deficiency, Autosomal Dominant 71
Protein C Deficiency, Autosomal Dominant 56
Protein C Deficiency Autosomal Dominant 73
Proc Deficiency, Autosomal Dominant 56
Proc Deficiency Autosomal Dominant 73

Characteristics:

OMIM:

56
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:

31
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:

OMIM 56 176860
OMIM Phenotypic Series 56 PS188050
UMLS 71 C2674321
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Summaries for Thrombophilia Due to Protein C Deficiency, Autosomal Dominant

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OMIM : 56 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, eye and liver, and related phenotypes are abnormality of the eye and abnormality of the nervous system

UniProtKB/Swiss-Prot : 73 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:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 abnormality of the eye 31 HP:0000478
2 abnormality of the nervous system 31 HP:0000707
3 pulmonary embolism 31 HP:0002204
4 hypercoagulability 31 HP:0100724
5 warfarin-induced skin necrosis 31 HP:0001038
6 deep venous thrombosis 31 HP:0002625
7 cerebral venous thrombosis 31 HP:0005305
8 reduced protein c activity 31 HP:0005543
9 superficial thrombophlebitis 31 HP:0002638

Symptoms via clinical synopsis from OMIM:

56
Respiratory Lung:
pulmonary embolism

Cardiovascular Vascular:
deep venous thrombosis
superficial thrombophlebitis

Laboratory Abnormalities:
plasma protein c deficiency

Skin Nails Hair Skin:
warfarin-induced skin necrosis

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:

40
Skin, Eye, Liver
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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. 56 6
10942114 2000
2
Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect. 56 6
8093743 1993
3
Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene. 6 56
2437584 1987
4
Mice with a severe deficiency in protein C display prothrombotic and proinflammatory phenotypes and compromised maternal reproductive capabilities. 56
15902301 2005
5
Symptomatic type 1 protein C deficiency caused by a de novo Ser270Leu mutation in the catalytic domain. 6
11380450 2001
6
Protein C deficiency related to valproic acid therapy: a possible association with childhood stroke. 56
11060540 2000
7
An unknown genetic defect increases venous thrombosis risk, through interaction with protein C deficiency. 6
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. 6
9553065 1998
9
Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly. 56
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. 6
8639775 1996
11
Recurrence of the PROC gene mutation R178Q: independent origins in Spanish protein C deficiency patients. 6
8807339 1996
12
Protein C deficiency: summary of the 1995 database update. 56
8594568 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. 56
7795227 1995
14
Population differences in the frequency of the factor V Leiden variant among people with clinically symptomatic protein C deficiency. 56
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. 56
7482420 1995
16
Disruption of a binding site for hepatocyte nuclear factor 1 in the protein C gene promoter is associated with hereditary thrombophilia. 6
7881411 1994
17
Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. 56
8049422 1994
18
Protein C and S deficiency, thrombophilia, and hypofibrinolysis: pathophysiologic causes of Legg-Perthes disease. 56
8047373 1994
19
Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis. 6
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. 6
8218861 1993
21
Dysfunctional protein C deficiency (type II). A report of 11 cases in 3 American families and review of the literature. 56
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. 56
8446940 1993
23
Impaired secretion of the elongated mutant of protein C (protein C-Nagoya). Molecular and cellular basis for hereditary protein C deficiency. 6
1469096 1992
24
A novel homozygous missense mutation in the protein C (PROC) gene causing recurrent venous thrombosis. 6
1511988 1992
25
Two different missense mutations at Arg 178 of the protein C (PROC) gene causing recurrent venous thrombosis. 6
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. 6
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. 6
1868249 1991
28
A new hereditary abnormal protein C (protein C Yonago) with a dysfunctional Gla-domain. 56
1771629 1991
29
Protein C London 1: recurrent mutation at Arg 169 (CGG----TGG) in the protein C gene causing thrombosis. 6
2602169 1989
30
The clinical spectrum of heterozygous protein C deficiency in a large New England kindred. 56
2521802 1989
31
Familial type II protein C deficiency associated with warfarin-induced skin necrosis and bilateral adrenal hemorrhage. 56
3189320 1988
32
A thrombotic state due to an abnormal protein C. 6
3185623 1988
33
A fatal thrombotic disorder associated with an acquired inhibitor of protein C. 56
3683503 1987
34
Childhood stroke associated with protein C or S deficiency. 56
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. 56
3463531 1986
36
Coumarin induced acral skin necrosis associated with hereditary protein C deficiency. 56
3755068 1986
37
The regulation of hemostasis: the protein C system. 56
3010107 1986
38
Prenatal diagnosis of hereditary protein C deficiency. 56
3840865 1985
39
Protein C deficiency in Austria. 56
3840917 1985
40
Congenital protein C deficiency and thrombotic disease in nine French families. 56
6437521 1984
41
Hereditary dysfunctional protein C (protein C Bergamo) and thrombosis. 56
6148564 1984
42
Characterization of a cDNA coding for human protein C. 6
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. 56
6547008 1984
44
Protein C deficiency in two Austrian families. 56
6665761 1983
45
Congenital protein C deficiency and venous thromboembolism. A study of three Dutch families. 56
6688122 1983
46
Deficiencies of protein C, an inhibitor of blood coagulation. 56
6125639 1982
47
Protein C deficiency in a Dutch family with thrombotic disease. 56
6897135 1982
48
Deficiency of protein C in congenital thrombotic disease. 56
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 106) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PROC NM_000312.3(PROC):c.1212dup (p.Pro405fs)duplication Pathogenic 407370 rs1333329860 2:128186342-128186343 2:127428766-127428767
2 PROC NM_000312.3(PROC):c.340G>T (p.Gly114Cys)SNV Pathogenic 522437 rs374476971 2:128180687-128180687 2:127423111-127423111
3 PROC NM_000312.4(PROC):c.321_325GCACG[3] (p.Cys111fs)short repeat Pathogenic 838069 2:128180666-128180667 2:127423090-127423091
4 PROC NM_000312.4(PROC):c.595C>T (p.Arg199Ter)SNV Pathogenic 839161 2:128183720-128183720 2:127426144-127426144
5 PROC NM_000312.3(PROC):c.889G>C (p.Asp297His)SNV Pathogenic 663591 2:128186025-128186025 2:127428449-127428449
6 PROC NM_000312.3(PROC):c.400+1G>ASNV Pathogenic 661205 2:128180748-128180748 2:127423172-127423172
7 PROC NM_000312.3(PROC):c.1042C>T (p.Arg348Ter)SNV Pathogenic 656 rs121918141 2:128186178-128186178 2:127428602-127428602
8 PROC NM_000312.3(PROC):c.1332G>C (p.Trp444Cys)SNV Pathogenic 657 rs121918142 2:128186468-128186468 2:127428892-127428892
9 PROC NM_000312.3(PROC):c.925G>A (p.Ala309Thr)SNV Pathogenic 662 rs121918146 2:128186061-128186061 2:127428485-127428485
10 PROC NM_000312.3(PROC):c.1000G>A (p.Gly334Ser)SNV Pathogenic 666 rs121918150 2:128186136-128186136 2:127428560-127428560
11 PROC NM_000312.3(PROC):c.658C>T (p.Arg220Trp)SNV Pathogenic 668 rs121918152 2:128183783-128183783 2:127426207-127426207
12 PROC NM_000312.3(PROC):c.552_553insTT (p.Arg185fs)insertion Pathogenic 672 rs1558715857 2:128183677-128183678 2:127426101-127426102
13 PROC NM_000312.3(PROC):c.678+9C>TSNV Pathogenic 673 rs1053253907 2:128183812-128183812 2:127426236-127426236
14 PROC NM_000312.3(PROC):c.678G>C (p.Gln226His)SNV Pathogenic 674 rs121918155 2:128183803-128183803 2:127426227-127426227
15 PROC NM_000312.3(PROC):c.1015G>A (p.Val339Met)SNV Pathogenic 677 rs121918158 2:128186151-128186151 2:127428575-127428575
16 PROC PROC, -14T-CSNV Pathogenic 678
17 PROC NM_000312.3(PROC):c.446A>C (p.His149Pro)SNV Pathogenic 679 rs121918159 2:128180895-128180895 2:127423319-127423319
18 PROC PROC, 1-BP DEL, 8857Gdeletion Pathogenic 670
19 PROC NM_000312.3(PROC):c.659G>A (p.Arg220Gln)SNV Pathogenic/Likely pathogenic 669 rs121918153 2:128183784-128183784 2:127426208-127426208
20 PROC NM_000312.3(PROC):c.631C>T (p.Arg211Trp)SNV Pathogenic/Likely pathogenic 659 rs121918143 2:128183756-128183756 2:127426180-127426180
21 PROC NM_000312.3(PROC):c.169C>T (p.Arg57Trp)SNV Pathogenic/Likely pathogenic 188230 rs757583846 2:128178957-128178957 2:127421381-127421381
22 PROC NM_000312.3(PROC):c.1201G>A (p.Asp401Asn)SNV Likely pathogenic 161334 rs142742242 2:128186337-128186337 2:127428761-127428761
23 PROC NM_000312.3(PROC):c.199G>A (p.Glu67Lys)SNV Likely pathogenic 623191 rs1448630830 2:128178987-128178987 2:127421411-127421411
24 PROC NM_000312.3(PROC):c.1166G>C (p.Gly389Ala)SNV Likely pathogenic 623192 rs1305782685 2:128186302-128186302 2:127428726-127428726
25 PROC NM_000312.3(PROC):c.814C>T (p.Arg272Cys)SNV Likely pathogenic 671 rs121918154 2:128185950-128185950 2:127428374-127428374
26 PROC NM_000312.3(PROC):c.125G>A (p.Arg42His)SNV Likely pathogenic 161333 rs369504169 2:128178913-128178913 2:127421337-127421337
27 PROC NM_000312.3(PROC):c.935C>T (p.Ser312Leu)SNV Likely pathogenic 680 rs121918160 2:128186071-128186071 2:127428495-127428495
28 PROC NM_000312.3(PROC):c.352T>C (p.Phe118Leu)SNV Likely pathogenic 469122 rs1553424043 2:128180699-128180699 2:127423123-127423123
29 PROC NM_000312.3(PROC):c.238-1G>ASNV Likely pathogenic 536971 rs1553423955 2:128180492-128180492 2:127422916-127422916
30 PROC NM_000312.3(PROC):c.811C>T (p.Arg271Trp)SNV Likely pathogenic 536970 rs767112991 2:128185947-128185947 2:127428371-127428371
31 PROC NM_000312.3(PROC):c.1242G>A (p.Trp414Ter)SNV Likely pathogenic 579043 rs1558718572 2:128186378-128186378 2:127428802-127428802
32 PROC NM_000312.3(PROC):c.30C>T (p.Phe10=)SNV Conflicting interpretations of pathogenicity 469121 rs148490199 2:128177548-128177548 2:127419972-127419972
33 PROC NM_000312.3(PROC):c.1272G>A (p.Glu424=)SNV Conflicting interpretations of pathogenicity 536973 rs770534863 2:128186408-128186408 2:127428832-127428832
34 PROC NM_000312.3(PROC):c.793C>T (p.Leu265Phe)SNV Conflicting interpretations of pathogenicity 675 rs121918156 2:128184795-128184795 2:127427219-127427219
35 PROC NM_000312.3(PROC):c.565C>T (p.Arg189Trp)SNV Conflicting interpretations of pathogenicity 161342 rs146922325 2:128183690-128183690 2:127426114-127426114
36 PROC NM_000312.3(PROC):c.962C>T (p.Pro321Leu)SNV Conflicting interpretations of pathogenicity 568712 rs1321566264 2:128186098-128186098 2:127428522-127428522
37 PROC NM_000312.3(PROC):c.-21-5C>TSNV Conflicting interpretations of pathogenicity 331101 rs41269833 2:128177493-128177493 2:127419917-127419917
38 PROC NM_000312.3(PROC):c.1299C>T (p.Gly433=)SNV Conflicting interpretations of pathogenicity 219771 rs151319700 2:128186435-128186435 2:127428859-127428859
39 PROC NM_000312.3(PROC):c.574_576AAG[1] (p.Lys193del)short repeat Conflicting interpretations of pathogenicity 225448 rs199469469 2:128183697-128183699 2:127426121-127426123
40 PROC NM_000312.3(PROC):c.1237A>G (p.Thr413Ala)SNV Conflicting interpretations of pathogenicity 237632 rs572021052 2:128186373-128186373 2:127428797-127428797
41 PROC NM_000312.4(PROC):c.1326C>T (p.Leu442=)SNV Conflicting interpretations of pathogenicity 706791 2:128186462-128186462 2:127428886-127428886
42 PROC NM_000312.3(PROC):c.1318C>T (p.Arg440Cys)SNV Uncertain significance 331113 rs886054848 2:128186454-128186454 2:127428878-127428878
43 PROC NM_000312.3(PROC):c.*220G>CSNV Uncertain significance 331116 rs886054849 2:128186742-128186742 2:127429166-127429166
44 PROC NM_000312.3(PROC):c.*170G>TSNV Uncertain significance 331115 rs563767423 2:128186692-128186692 2:127429116-127429116
45 PROC NM_000312.3(PROC):c.-55C>TSNV Uncertain significance 331099 rs886054845 2:128176035-128176035 2:127418459-127418459
46 PROC NM_000312.3(PROC):c.*146T>CSNV Uncertain significance 331114 rs140461934 2:128186668-128186668 2:127429092-127429092
47 PROC NM_000312.3(PROC):c.666C>G (p.Asp222Glu)SNV Uncertain significance 331107 rs771116175 2:128183791-128183791 2:127426215-127426215
48 PROC NM_000312.3(PROC):c.1043G>A (p.Arg348Gln)SNV Uncertain significance 225449 rs201827066 2:128186179-128186179 2:127428603-127428603
49 PROC NM_000312.3(PROC):c.91G>A (p.Glu31Lys)SNV Uncertain significance 237635 rs779710709 2:128178879-128178879 2:127421303-127421303
50 PROC NM_000312.3(PROC):c.286C>T (p.Pro96Ser)SNV Uncertain significance 237633 rs774908523 2:128180633-128180633 2:127423057-127423057

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

73 (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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 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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