THPH5
MCID: THR089
MIFTS: 27

Thrombophilia Due to Protein S Deficiency, Autosomal Dominant (THPH5)

Categories: Blood diseases, Genetic diseases

Aliases & Classifications for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

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

Name: Thrombophilia Due to Protein S Deficiency, Autosomal Dominant 56 73 13 71
Thph5 56 73
Thrombophilia Autosomal Recessive Due to Protein S Deficiency 73
Thrombophilia Autosomal Dominant Due to Protein S Deficiency 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
protein s deficiency is found in 2-3% of patients with thromboembolism
acquired protein s deficiency seen in pregnancy, oral contraceptive use, warfarin use, liver disease, dic, and diabetes


HPO:

31
thrombophilia due to protein s deficiency, autosomal dominant:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 56 612336
OMIM Phenotypic Series 56 PS188050
MeSH 43 D018455
UMLS 71 C3278211

Summaries for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

OMIM : 56 Heterozygous protein S deficiency, like protein C deficiency (176860), is characterized by recurrent venous thrombosis. Bertina (1990) classified protein S deficiency into 3 clinical subtypes based on laboratory findings. Type I refers to deficiency of both free and total protein S as well as decreased protein S activity; type II shows normal plasma values, but decreased protein S activity; and type III shows decreased free protein S levels and activity, but normal total protein S levels. Approximately 40% of protein S circulates as a free active form, whereas the remaining 60% circulates as an inactive form bound to C4BPA (120830). Zoller et al. (1995) observed coexistence of type I and type III PROS1-deficient phenotypes within a single family and determined that the subtypes are allelic. Under normal conditions, the concentration of protein S exceeds that of C4BPA by approximately 30 to 40%. Thus, free protein S is the molar surplus of protein S over C4BPA. Mild protein S deficiency will thus present with selective deficiency of free protein S, whereas more pronounced protein S deficiency will also decrease the complexed protein S and consequently the total protein S level. These findings explained why assays for free protein S have a higher predictive value for protein S deficiency. See also autosomal recessive thrombophilia due to protein S deficiency (THPH6; 614514), which is a more severe disorder. (612336)

MalaCards based summary : Thrombophilia Due to Protein S Deficiency, Autosomal Dominant, also known as thph5, is related to thrombophilia due to protein s deficiency, autosomal recessive. An important gene associated with Thrombophilia Due to Protein S Deficiency, Autosomal Dominant is PROS1 (Protein S). Affiliated tissues include liver, skin and bone, and related phenotypes are hypercoagulability and pulmonary embolism

UniProtKB/Swiss-Prot : 73 Thrombophilia due to protein S deficiency, autosomal dominant: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Based on the plasma levels of total and free PROS1 as well as the serine protease-activated protein C cofactor activity, three types of THPH5 have been described: type I, characterized by reduced total and free PROS1 levels together with reduced anticoagulant activity; type III, in which only free PROS1 antigen and PROS1 activity levels are reduced; and the rare type II which is characterized by normal concentrations of both total and free PROS1 antigen, but low cofactor activity.

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

Diseases related to Thrombophilia Due to Protein S Deficiency, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 thrombophilia due to protein s deficiency, autosomal recessive 11.3

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

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

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 hypercoagulability 31 HP:0100724
2 pulmonary embolism 31 HP:0002204
3 purpura 31 HP:0000979
4 arterial thrombosis 31 HP:0004420
5 warfarin-induced skin necrosis 31 HP:0001038
6 superficial thrombophlebitis 31 HP:0002638
7 cerebral venous thrombosis 31 HP:0005305
8 reduced protein s activity 31 HP:0004855

Symptoms via clinical synopsis from OMIM:

56
Respiratory Lung:
pulmonary embolism

Skin Nails Hair Skin:
warfarin-induced skin necrosis

Cardiovascular Vascular:
arterial thrombosis
superficial thrombophlebitis
cerebral venous thrombosis
venous thrombosis, recurrent
mesenteric thrombosis

Laboratory Abnormalities:
absent/reduced protein s and normal total proteins in heterozygote

Clinical features from OMIM:

612336

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

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

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

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

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

40
Liver, Skin, Bone

Publications for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

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

(show all 27)
# Title Authors PMID Year
1
Genetic predisposition of white matter infarction with protein S deficiency and R355C mutation. 56 6
21172841 2010
2
Protein S gene analysis reveals the presence of a cosegregating mutation in most pedigrees with type I but not type III PS deficiency. 56 6
10447256 1999
3
Detection and characterization of seven novel protein S (PROS) gene lesions: evaluation of reverse transcript-polymerase chain reaction as a mutation screening strategy. 56 6
7545463 1995
4
The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. 6
20027064 2010
5
Gross deletions/duplications in PROS1 are relatively common in point mutation-negative hereditary protein S deficiency. 56
19466456 2009
6
Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in families with inherited deficiencies of protein S. 56
10706858 2000
7
A novel mutation in intron K of the PROS1 gene causes aberrant RNA splicing and is a common cause of protein S deficiency in a UK thrombophilia cohort. 6
9657428 1998
8
Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease. 56
7780139 1995
9
Deficiency of both protein C and protein S in a family with ischemic strokes in young adults. 56
8035922 1994
10
Three novel mutations in five unrelated subjects with hereditary protein S deficiency type I. 6
8113388 1994
11
Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S. 6
8298131 1994
12
Autoimmune protein S deficiency. 56
8247052 1993
13
Brief report: autoimmune protein S deficiency in a boy with severe thromboembolic disease. 56
8497285 1993
14
Purpura fulminans due to protein S deficiency following chickenpox. 56
1386247 1992
15
Protein-S, a vitamin K-dependent protein, is a bone matrix component synthesized and secreted by osteoblasts. 56
1531628 1992
16
Mesenteric vein thrombosis associated with a familial deficiency of free protein S. 56
1828142 1991
17
Hereditary protein S deficiency in young adults with arterial occlusive disease. 56
2148653 1990
18
Protein S deficiency associated with central retinal artery occlusion. 56
2142417 1990
19
Bone mineral density and its association with inherited protein S deficiency. 56
2141197 1990
20
Heterozygous protein-S deficiency: a study of a large kindred. 56
2147089 1990
21
Free protein S deficiency: a possible association with cerebrovascular occlusion. 56
2531944 1989
22
A new case of 'type II' inherited protein S deficiency. 56
2532929 1989
23
Familial dysfunction of protein S. 56
2530648 1989
24
Hereditary protein S deficiency: clinical manifestations. 56
2952034 1987
25
A protein S deficient family with portal vein thrombosis. 56
2935967 1985
26
Recurrent venous thromboembolism in patients with a partial deficiency of protein S. 56
6239102 1984
27
Plasma protein S deficiency in familial thrombotic disease. 56
6238642 1984

Variations for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

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

6 (show top 50) (show all 61) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PROS1 NM_001314077.1(PROS1):c.869A>G (p.Asn290Ser)SNV Pathogenic 13317 rs121918473 3:93617368-93617368 3:93898524-93898524
2 PROS1 NM_001314077.1(PROS1):c.682A>G (p.Lys228Glu)SNV Pathogenic 13318 rs121918474 3:93624643-93624643 3:93905799-93905799
3 PROS1 PROS1, IVS10DS, G-A, +5SNV Pathogenic 13319
4 PROS1 NM_001314077.1(PROS1):c.2127A>T (p.Ter709Tyr)SNV Pathogenic 13320 rs267606981 3:93593089-93593089 3:93874245-93874245
5 PROS1 PROS1, IVS11AS, A-G, -9SNV Pathogenic 13321
6 PROS1 NM_001314077.1(PROS1):c.931C>T (p.Gln311Ter)SNV Pathogenic 13322 rs121918475 3:93617306-93617306 3:93898462-93898462
7 PROS1 NM_001314077.1(PROS1):c.1159C>T (p.Arg387Cys)SNV Pathogenic 29846 rs387906674 3:93611869-93611869 3:93893025-93893025
8 PROS1 NM_001314077.1(PROS1):c.824-1G>ASNV Likely pathogenic 162509 rs368074804 3:93617414-93617414 3:93898570-93898570
9 PROS1 NM_001314077.1(PROS1):c.76+7A>GSNV Conflicting interpretations of pathogenicity 215729 rs201928951 3:93692511-93692511 3:93973667-93973667
10 PROS1 NM_001314077.1(PROS1):c.1597T>C (p.Ser533Pro)SNV Conflicting interpretations of pathogenicity 13316 rs121918472 3:93598150-93598150 3:93879306-93879306
11 PROS1 NM_001314077.1(PROS1):c.380G>A (p.Gly127Glu)SNV Conflicting interpretations of pathogenicity 161354 rs144526169 3:93629525-93629525 3:93910681-93910681
12 PROS1 NM_001314077.1(PROS1):c.1191T>G (p.Asn397Lys)SNV Conflicting interpretations of pathogenicity 161352 rs199469491 3:93611837-93611837 3:93892993-93892993
13 PROS1 NM_001314077.1(PROS1):c.794G>A (p.Arg265Lys)SNV Conflicting interpretations of pathogenicity 161346 rs41267007 3:93619677-93619677 3:93900833-93900833
14 PROS1 NM_001314077.1(PROS1):c.215G>T (p.Arg72Leu)SNV Conflicting interpretations of pathogenicity 346893 rs7614835 3:93646209-93646209 3:93927365-93927365
15 PROS1 NM_001314077.1(PROS1):c.1473A>G (p.Gly491=)SNV Conflicting interpretations of pathogenicity 346882 rs371312357 3:93603687-93603687 3:93884843-93884843
16 PROS1 NM_001314077.1(PROS1):c.1590T>C (p.Asn530=)SNV Conflicting interpretations of pathogenicity 346881 rs76877671 3:93598157-93598157 3:93879313-93879313
17 PROS1 NM_001314077.1(PROS1):c.1117G>A (p.Ala373Thr)SNV Conflicting interpretations of pathogenicity 346885 rs189883848 3:93611911-93611911 3:93893067-93893067
18 PROS1 NM_001314077.1(PROS1):c.806A>C (p.Lys269Thr)SNV Uncertain significance 346887 rs558211174 3:93619665-93619665 3:93900821-93900821
19 PROS1 NM_001314077.1(PROS1):c.681T>C (p.Asn227=)SNV Uncertain significance 346890 rs372109285 3:93624644-93624644 3:93905800-93905800
20 PROS1 NM_001314077.1(PROS1):c.599A>G (p.Asn200Ser)SNV Uncertain significance 346891 rs144430063 3:93624726-93624726 3:93905882-93905882
21 PROS1 NM_000313.4(PROS1):c.1871-14T>GSNV Uncertain significance 801989 3:93593263-93593263 3:93874419-93874419
22 PROS1 NM_001314077.1(PROS1):c.*86T>CSNV Uncertain significance 346879 rs886058925 3:93593003-93593003 3:93874159-93874159
23 PROS1 NM_001314077.1(PROS1):c.*370G>ASNV Uncertain significance 346873 rs144135580 3:93592719-93592719 3:93873875-93873875
24 PROS1 NM_001314077.1(PROS1):c.901G>A (p.Gly301Arg)SNV Uncertain significance 346886 rs886058927 3:93617336-93617336 3:93898492-93898492
25 PROS1 NM_001314077.1(PROS1):c.330G>A (p.Thr110=)SNV Uncertain significance 346892 rs145399944 3:93646094-93646094 3:93927250-93927250
26 PROS1 NM_001314077.1(PROS1):c.-60G>CSNV Uncertain significance 346896 rs368555701 3:93692653-93692653 3:93973809-93973809
27 PROS1 NM_001314077.1(PROS1):c.-62T>GSNV Uncertain significance 346897 rs556711298 3:93692655-93692655 3:93973811-93973811
28 PROS1 NM_001314077.1(PROS1):c.207T>C (p.Val69=)SNV Uncertain significance 346894 rs886058928 3:93646217-93646217 3:93927373-93927373
29 PROS1 NM_001314077.1(PROS1):c.-261C>TSNV Uncertain significance 346900 rs886058930 3:93692854-93692854 3:93974010-93974010
30 PROS1 NM_001314077.1(PROS1):c.*119T>CSNV Uncertain significance 346878 rs886058924 3:93592970-93592970 3:93874126-93874126
31 PROS1 NM_001314077.1(PROS1):c.2099C>T (p.Ser700Leu)SNV Uncertain significance 346880 rs886058926 3:93593117-93593117 3:93874273-93874273
32 PROS1 NM_001314077.1(PROS1):c.1419+8T>GSNV Uncertain significance 346883 rs778473220 3:93605172-93605172 3:93886328-93886328
33 PROS1 NM_001314077.1(PROS1):c.780C>T (p.Cys260=)SNV Uncertain significance 346888 rs377173471 3:93619691-93619691 3:93900847-93900847
34 PROS1 NM_001314077.1(PROS1):c.697+12A>GSNV Uncertain significance 346889 rs753550053 3:93624616-93624616 3:93905772-93905772
35 PROS1 NM_001314077.1(PROS1):c.-116C>TSNV Uncertain significance 346898 rs886058929 3:93692709-93692709 3:93973865-93973865
36 PROS1 NM_001314077.1(PROS1):c.-135C>TSNV Uncertain significance 346899 rs750502941 3:93692728-93692728 3:93973884-93973884
37 PROS1 NM_001314077.1(PROS1):c.*1167_*1170deldeletion Uncertain significance 346865 rs886058921 3:93591919-93591922 3:93873075-93873078
38 PROS1 NM_001314077.1(PROS1):c.*1139C>ASNV Uncertain significance 346866 rs886058922 3:93591950-93591950 3:93873106-93873106
39 PROS1 NM_001314077.1(PROS1):c.*783C>TSNV Uncertain significance 346867 rs137965257 3:93592306-93592306 3:93873462-93873462
40 PROS1 NM_001314077.1(PROS1):c.*693G>ASNV Uncertain significance 346869 rs189450409 3:93592396-93592396 3:93873552-93873552
41 PROS1 NM_001314077.1(PROS1):c.*686G>ASNV Uncertain significance 346870 rs550909963 3:93592403-93592403 3:93873559-93873559
42 PROS1 NM_001314077.1(PROS1):c.*422G>TSNV Uncertain significance 346872 rs770100925 3:93592667-93592667 3:93873823-93873823
43 PROS1 NM_001314077.1(PROS1):c.*301A>GSNV Uncertain significance 346874 rs569117154 3:93592788-93592788 3:93873944-93873944
44 PROS1 NM_001314077.1(PROS1):c.-43G>ASNV Uncertain significance 346895 rs370938580 3:93692636-93692636 3:93973792-93973792
45 PROS1 NM_001314077.1(PROS1):c.*221deldeletion Uncertain significance 346875 rs776969264 3:93592868-93592868 3:93874024-93874024
46 PROS1 NM_001314077.1(PROS1):c.*714T>CSNV Uncertain significance 346868 rs886058923 3:93592375-93592375 3:93873531-93873531
47 PROS1 NM_001314077.1(PROS1):c.*155T>ASNV Uncertain significance 346877 rs534064879 3:93592934-93592934 3:93874090-93874090
48 PROS1 NM_001314077.1(PROS1):c.772T>A (p.Cys258Ser)SNV Uncertain significance 161353 rs370855515 3:93619699-93619699 3:93900855-93900855
49 PROS1 NM_001314077.1(PROS1):c.527C>A (p.Thr176Asn)SNV Uncertain significance 161347 rs146366248 3:93624903-93624903 3:93906059-93906059
50 PROS1 NM_001314077.1(PROS1):c.1042C>T (p.Arg348Cys)SNV Uncertain significance 161345 rs373983977 3:93615439-93615439 3:93896595-93896595

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

73 (show top 50) (show all 88)
# Symbol AA change Variation ID SNP ID
1 PROS1 p.Lys196Glu VAR_005566 rs121918474
2 PROS1 p.Asn258Ser VAR_005567 rs121918473
3 PROS1 p.Gly482Cys VAR_014116
4 PROS1 p.Tyr485Cys VAR_014117 rs132366395
5 PROS1 p.Arg561Gly VAR_014119 rs121918476
6 PROS1 p.Thr78Met VAR_014666 rs6122
7 PROS1 p.Leu15His VAR_046802
8 PROS1 p.Val18Glu VAR_046803
9 PROS1 p.Arg40Leu VAR_046804 rs7614835
10 PROS1 p.Arg41His VAR_046805 rs963668412
11 PROS1 p.Lys50Glu VAR_046806 rs748630360
12 PROS1 p.Gly52Asp VAR_046807
13 PROS1 p.Glu67Ala VAR_046808 rs766423432
14 PROS1 p.Ala68Asp VAR_046809
15 PROS1 p.Phe72Cys VAR_046810
16 PROS1 p.Val87Leu VAR_046812 rs557733421
17 PROS1 p.Cys88Tyr VAR_046813
18 PROS1 p.Arg90Cys VAR_046814 rs765935815
19 PROS1 p.Arg90His VAR_046815 rs200886866
20 PROS1 p.Gly95Glu VAR_046816 rs144526169
21 PROS1 p.Gly95Arg VAR_046817
22 PROS1 p.Arg101Cys VAR_046819 rs778731080
23 PROS1 p.Arg111Ser VAR_046820
24 PROS1 p.Cys121Tyr VAR_046821
25 PROS1 p.Asp129Gly VAR_046822 rs749024073
26 PROS1 p.Thr144Asn VAR_046823 rs146366248
27 PROS1 p.Trp149Cys VAR_046824
28 PROS1 p.Asp157Gly VAR_046825 rs751090951
29 PROS1 p.Cys161Gly VAR_046826
30 PROS1 p.Asn166Tyr VAR_046827
31 PROS1 p.Cys175Phe VAR_046829
32 PROS1 p.Cys186Tyr VAR_046830 rs779391826
33 PROS1 p.Glu204Gly VAR_046831
34 PROS1 p.Cys241Ser VAR_046833
35 PROS1 p.Asp243Asn VAR_046834
36 PROS1 p.Asp245Gly VAR_046835 rs121111720
37 PROS1 p.Cys247Gly VAR_046836
38 PROS1 p.Glu249Lys VAR_046837 rs145567581
39 PROS1 p.Cys265Arg VAR_046838
40 PROS1 p.Cys265Trp VAR_046839
41 PROS1 p.Tyr266Cys VAR_046840 rs777616039
42 PROS1 p.Cys267Ser VAR_046841
43 PROS1 p.Leu300Pro VAR_046842
44 PROS1 p.Ser324Pro VAR_046843
45 PROS1 p.Gly336Asp VAR_046844
46 PROS1 p.Gly336Ser VAR_046845
47 PROS1 p.Gly336Val VAR_046846
48 PROS1 p.Leu339Pro VAR_046847
49 PROS1 p.Leu351Pro VAR_046848
50 PROS1 p.Arg355His VAR_046849 rs780863931

Expression for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

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

Pathways for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

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

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