THPH5
MCID: THR089
MIFTS: 21

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 58 76 13 74
Thph5 58 76
Thrombophilia Autosomal Recessive Due to Protein S Deficiency 76
Thrombophilia Autosomal Dominant Due to Protein S Deficiency 76

Characteristics:

OMIM:

58
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:

33
thrombophilia due to protein s deficiency, autosomal dominant:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

OMIM : 58 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 skin, and related phenotypes are hypercoagulability and pulmonary embolism

UniProtKB/Swiss-Prot : 76 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 11.1

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

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

33 (show all 8)
# Description HPO Frequency HPO Source Accession
1 hypercoagulability 33 HP:0100724
2 pulmonary embolism 33 HP:0002204
3 purpura 33 HP:0000979
4 arterial thrombosis 33 HP:0004420
5 warfarin-induced skin necrosis 33 HP:0001038
6 superficial thrombophlebitis 33 HP:0002638
7 cerebral venous thrombosis 33 HP:0005305
8 reduced protein s activity 33 HP:0004855

Symptoms via clinical synopsis from OMIM:

58
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:

42
Skin

Publications for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

Variations for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

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

76 (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

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

6 (show top 50) (show all 118)
# Gene Variation Type Significance SNP ID Assembly Location
1 PROS1 NM_000313.3(PROS1): c.1501T> C (p.Ser501Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs121918472 GRCh37 Chromosome 3, 93598150: 93598150
2 PROS1 NM_000313.3(PROS1): c.1501T> C (p.Ser501Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs121918472 GRCh38 Chromosome 3, 93879306: 93879306
3 PROS1 NM_000313.3(PROS1): c.773A> G (p.Asn258Ser) single nucleotide variant Pathogenic rs121918473 GRCh37 Chromosome 3, 93617368: 93617368
4 PROS1 NM_000313.3(PROS1): c.773A> G (p.Asn258Ser) single nucleotide variant Pathogenic rs121918473 GRCh38 Chromosome 3, 93898524: 93898524
5 PROS1 NM_000313.3(PROS1): c.586A> G (p.Lys196Glu) single nucleotide variant Pathogenic rs121918474 GRCh37 Chromosome 3, 93624643: 93624643
6 PROS1 NM_000313.3(PROS1): c.586A> G (p.Lys196Glu) single nucleotide variant Pathogenic rs121918474 GRCh38 Chromosome 3, 93905799: 93905799
7 PROS1 PROS1, IVS10DS, G-A, +5 single nucleotide variant Pathogenic
8 PROS1 NM_000313.3(PROS1): c.2031A> T (p.Ter677Tyr) single nucleotide variant Pathogenic rs267606981 GRCh37 Chromosome 3, 93593089: 93593089
9 PROS1 NM_000313.3(PROS1): c.2031A> T (p.Ter677Tyr) single nucleotide variant Pathogenic rs267606981 GRCh38 Chromosome 3, 93874245: 93874245
10 PROS1 PROS1, IVS11AS, A-G, -9 single nucleotide variant Pathogenic
11 PROS1 NM_000313.3(PROS1): c.835C> T (p.Gln279Ter) single nucleotide variant Pathogenic rs121918475 GRCh37 Chromosome 3, 93617306: 93617306
12 PROS1 NM_000313.3(PROS1): c.835C> T (p.Gln279Ter) single nucleotide variant Pathogenic rs121918475 GRCh38 Chromosome 3, 93898462: 93898462
13 PROS1 NM_000313.3(PROS1): c.1681C> G (p.Arg561Gly) single nucleotide variant Pathogenic rs121918476 GRCh37 Chromosome 3, 93595999: 93595999
14 PROS1 NM_000313.3(PROS1): c.1681C> G (p.Arg561Gly) single nucleotide variant Pathogenic rs121918476 GRCh38 Chromosome 3, 93877155: 93877155
15 PROS1 NM_000313.3(PROS1): c.1063C> T (p.Arg355Cys) single nucleotide variant Pathogenic rs387906674 GRCh37 Chromosome 3, 93611869: 93611869
16 PROS1 NM_000313.3(PROS1): c.1063C> T (p.Arg355Cys) single nucleotide variant Pathogenic rs387906674 GRCh38 Chromosome 3, 93893025: 93893025
17 PROS1 NM_000313.3(PROS1): c.1747A> C (p.Asn583His) single nucleotide variant Uncertain significance rs139479630 GRCh38 Chromosome 3, 93877089: 93877089
18 PROS1 NM_000313.3(PROS1): c.1907A> G (p.Tyr636Cys) single nucleotide variant Uncertain significance rs368173480 GRCh37 Chromosome 3, 93593213: 93593213
19 PROS1 NM_000313.3(PROS1): c.1907A> G (p.Tyr636Cys) single nucleotide variant Uncertain significance rs368173480 GRCh38 Chromosome 3, 93874369: 93874369
20 PROS1 NM_000313.3(PROS1): c.1762A> G (p.Thr588Ala) single nucleotide variant Benign rs142846443 GRCh37 Chromosome 3, 93595918: 93595918
21 PROS1 NM_000313.3(PROS1): c.1762A> G (p.Thr588Ala) single nucleotide variant Benign rs142846443 GRCh38 Chromosome 3, 93877074: 93877074
22 PROS1 NM_000313.3(PROS1): c.1747A> C (p.Asn583His) single nucleotide variant Uncertain significance rs139479630 GRCh37 Chromosome 3, 93595933: 93595933
23 PROS1 NM_000313.3(PROS1): c.1594A> G (p.Thr532Ala) single nucleotide variant Uncertain significance rs371028997 GRCh37 Chromosome 3, 93598057: 93598057
24 PROS1 NM_000313.3(PROS1): c.1594A> G (p.Thr532Ala) single nucleotide variant Uncertain significance rs371028997 GRCh38 Chromosome 3, 93879213: 93879213
25 PROS1 NM_000313.3(PROS1): c.1528G> A (p.Val510Met) single nucleotide variant Benign rs138925964 GRCh37 Chromosome 3, 93598123: 93598123
26 PROS1 NM_000313.3(PROS1): c.1528G> A (p.Val510Met) single nucleotide variant Benign rs138925964 GRCh38 Chromosome 3, 93879279: 93879279
27 PROS1 NM_000313.3(PROS1): c.1331C> T (p.Pro444Leu) single nucleotide variant Uncertain significance rs369244777 GRCh37 Chromosome 3, 93603733: 93603733
28 PROS1 NM_000313.3(PROS1): c.1331C> T (p.Pro444Leu) single nucleotide variant Uncertain significance rs369244777 GRCh38 Chromosome 3, 93884889: 93884889
29 PROS1 NM_000313.3(PROS1): c.1095T> G (p.Asn365Lys) single nucleotide variant Uncertain significance rs199469491 GRCh37 Chromosome 3, 93611837: 93611837
30 PROS1 NM_000313.3(PROS1): c.1095T> G (p.Asn365Lys) single nucleotide variant Uncertain significance rs199469491 GRCh38 Chromosome 3, 93892993: 93892993
31 PROS1 NM_000313.3(PROS1): c.946C> T (p.Arg316Cys) single nucleotide variant Uncertain significance rs373983977 GRCh37 Chromosome 3, 93615439: 93615439
32 PROS1 NM_000313.3(PROS1): c.946C> T (p.Arg316Cys) single nucleotide variant Uncertain significance rs373983977 GRCh38 Chromosome 3, 93896595: 93896595
33 PROS1 NM_000313.3(PROS1): c.698G> A (p.Arg233Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs41267007 GRCh37 Chromosome 3, 93619677: 93619677
34 PROS1 NM_000313.3(PROS1): c.698G> A (p.Arg233Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs41267007 GRCh38 Chromosome 3, 93900833: 93900833
35 PROS1 NM_000313.3(PROS1): c.676T> A (p.Cys226Ser) single nucleotide variant Uncertain significance rs370855515 GRCh37 Chromosome 3, 93619699: 93619699
36 PROS1 NM_000313.3(PROS1): c.676T> A (p.Cys226Ser) single nucleotide variant Uncertain significance rs370855515 GRCh38 Chromosome 3, 93900855: 93900855
37 PROS1 NM_000313.3(PROS1): c.431C> A (p.Thr144Asn) single nucleotide variant Uncertain significance rs146366248 GRCh37 Chromosome 3, 93624903: 93624903
38 PROS1 NM_000313.3(PROS1): c.431C> A (p.Thr144Asn) single nucleotide variant Uncertain significance rs146366248 GRCh38 Chromosome 3, 93906059: 93906059
39 PROS1 NM_000313.3(PROS1): c.284G> A (p.Gly95Glu) single nucleotide variant Uncertain significance rs144526169 GRCh37 Chromosome 3, 93629525: 93629525
40 PROS1 NM_000313.3(PROS1): c.284G> A (p.Gly95Glu) single nucleotide variant Uncertain significance rs144526169 GRCh38 Chromosome 3, 93910681: 93910681
41 PROS1 NM_000313.3(PROS1): c.728-1G> A single nucleotide variant Likely pathogenic rs368074804 GRCh37 Chromosome 3, 93617414: 93617414
42 PROS1 NM_000313.3(PROS1): c.728-1G> A single nucleotide variant Likely pathogenic rs368074804 GRCh38 Chromosome 3, 93898570: 93898570
43 PROS1 NM_000313.3(PROS1): c.76+7A> G single nucleotide variant Conflicting interpretations of pathogenicity rs201928951 GRCh38 Chromosome 3, 93973667: 93973667
44 PROS1 NM_000313.3(PROS1): c.76+7A> G single nucleotide variant Conflicting interpretations of pathogenicity rs201928951 GRCh37 Chromosome 3, 93692511: 93692511
45 PROS1 NM_000313.3(PROS1): c.2001A> G (p.Pro667=) single nucleotide variant Benign/Likely benign rs6123 GRCh37 Chromosome 3, 93593119: 93593119
46 PROS1 NM_000313.3(PROS1): c.2001A> G (p.Pro667=) single nucleotide variant Benign/Likely benign rs6123 GRCh38 Chromosome 3, 93874275: 93874275
47 PROS1 NM_000313.3(PROS1): c.*197C> T single nucleotide variant Likely benign rs182088150 GRCh38 Chromosome 3, 93874048: 93874048
48 PROS1 NM_000313.3(PROS1): c.*197C> T single nucleotide variant Likely benign rs182088150 GRCh37 Chromosome 3, 93592892: 93592892
49 PROS1 NM_000313.3(PROS1): c.*155T> A single nucleotide variant Uncertain significance rs534064879 GRCh38 Chromosome 3, 93874090: 93874090
50 PROS1 NM_000313.3(PROS1): c.*155T> A single nucleotide variant Uncertain significance rs534064879 GRCh37 Chromosome 3, 93592934: 93592934

Expression for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

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Pathways for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

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

Sources for Thrombophilia Due to Protein S Deficiency, Autosomal Dominant

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