THPH4
MCID: THR068
MIFTS: 27

Thrombophilia Due to Protein C Deficiency, Autosomal Recessive (THPH4)

Categories: Blood diseases, Bone diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Thrombophilia Due to Protein C Deficiency, Autosomal Recessive

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

Name: Thrombophilia Due to Protein C Deficiency, Autosomal Recessive 58 54 76 13 74
Thrombophilia, Hereditary, Due to Protein C Deficiency, Autosomal Recessive 30 6 41
Autosomal Recessive Thrombophilia Due to Congenital Protein C Deficiency 54 60
Severe Hereditary Thrombophilia Due to Congenital Protein C Deficiency 54 60
Autosomal Recessive Thrombophilia Due to Pc Deficiency 54 60
Thph4 58 76
Autosomal Recessive Hereditary Thrombophilia Due to Protein C Deficiency 54
Hereditary Thrombophilia Due to Congenital Protein C Deficiency 54
Hereditary Thrombophilia Due to Pc Deficiency 54
Protein C Deficiency, Autosomal Recessive 58
Autosomal Recessive Protein C Deficiency 54
Protein C Deficiency Autosomal Recessive 76
Proc Deficiency, Autosomal Recessive 58
Proc Deficiency Autosomal Recessive 76

Characteristics:

Orphanet epidemiological data:

60
severe hereditary thrombophilia due to congenital protein c deficiency
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
see also autosomal dominant form
may be lethal in infancy if untreated
occasional late-onset of symptoms with homozygosity (e.g. protein c deficiency, homozygous)


HPO:

33
thrombophilia due to protein c deficiency, autosomal recessive:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Thrombophilia Due to Protein C Deficiency, Autosomal Recessive

NIH Rare Diseases : 54 Autosomal recessiveprotein C deficiency is an inherited blood clotting disorder characterized by serious protein C deficiency. The disease may be very severe and associated with neonatal purpura fulminans (NPF) or intracranial thromboembolism. It may also be a milder disorder where patients present with clotting (venous thromboembolism) in childhood, adolescence, or adulthood.  It is caused by having changes in the PROC gene. The inheritance pattern is autosomal recessive. Treatment depends on the severity of the disease and may involve blood thinners, clot-dissolving medicines, or blood transfusions of fresh frozen plasma or highly purified protein C concentrate. In some cases, live donor liver transplantation which cures the disease.

MalaCards based summary : Thrombophilia Due to Protein C Deficiency, Autosomal Recessive, also known as thrombophilia, hereditary, due to protein c deficiency, autosomal recessive, is related to protein c deficiency, and has symptoms including seizures An important gene associated with Thrombophilia Due to Protein C Deficiency, Autosomal Recessive is PROC (Protein C, Inactivator Of Coagulation Factors Va And VIIIa). Affiliated tissues include skin, and related phenotypes are thin skin and venous thrombosis

OMIM : 58 Autosomal recessive protein C deficiency resulting from homozygous or compound heterozygous PROC mutations is a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia (Millar et al., 2000). (612304)

UniProtKB/Swiss-Prot : 76 Thrombophilia due to protein C deficiency, autosomal recessive: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare.

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

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

# Related Disease Score Top Affiliating Genes
1 protein c deficiency 11.5

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

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

60 33 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 thin skin 60 33 frequent (33%) Frequent (79-30%) HP:0000963
2 venous thrombosis 60 33 frequent (33%) Frequent (79-30%) HP:0004936
3 purpura 60 33 frequent (33%) Frequent (79-30%) HP:0000979
4 pulmonary embolism 60 33 occasional (7.5%) Occasional (29-5%) HP:0002204
5 abnormality of the cerebral vasculature 60 33 occasional (7.5%) Occasional (29-5%) HP:0100659
6 venous insufficiency 60 33 occasional (7.5%) Occasional (29-5%) HP:0005293
7 abnormality of skin pigmentation 60 33 occasional (7.5%) Occasional (29-5%) HP:0001000
8 gangrene 60 33 occasional (7.5%) Occasional (29-5%) HP:0100758
9 warfarin-induced skin necrosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0001038
10 seizures 33 HP:0001250
11 global developmental delay 33 HP:0001263
12 hypercoagulability 33 HP:0100724
13 aplasia/hypoplasia of the skin 60 Frequent (79-30%)
14 cerebral palsy 33 HP:0100021
15 deep venous thrombosis 33 HP:0002625
16 superficial thrombophlebitis 33 HP:0002638
17 vitreous hemorrhage 33 HP:0007902
18 reduced protein c activity 33 HP:0005543

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
seizures
developmental delay
spastic cerebral palsy
periventricular hemorrhagic infarction

Cardiovascular Vascular:
deep venous thrombosis
superficial thrombophlebitis
intraabdominal venous thrombosis

Head And Neck Eyes:
neonatal vitreous hemorrhages

Respiratory Lung:
pulmonary embolism

Laboratory Abnormalities:
plasma protein c deficiency

Skin Nails Hair Skin:
neonatal purpura fulminans

Clinical features from OMIM:

612304

UMLS symptoms related to Thrombophilia Due to Protein C Deficiency, Autosomal Recessive:


seizures

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

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

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

Genetic tests related to Thrombophilia Due to Protein C Deficiency, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Thrombophilia, Hereditary, Due to Protein C Deficiency, Autosomal Recessive 30 PROC

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

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

42
Skin

Publications for Thrombophilia Due to Protein C Deficiency, Autosomal Recessive

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

# Title Authors Year
1
Molecular genetic analysis of severe protein C deficiency. ( 10942114 )
2000
2
Compound heterozygosity in a family with protein C deficiency illustrating the complexity of the underlying molecular mechanism. ( 8128429 )
1993
3
Homozygous protein C deficiency with late onset and recurrent coumarin-induced skin necrosis. ( 1347608 )
1992
4
Protein CVermont: symptomatic type II protein C deficiency associated with two GLA domain mutations. ( 1347706 )
1992
5
Protein C deficiency and thromboembolism: recurrent mutation at Arg 306 in the protein C gene. ( 1348046 )
1992
6
Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C. ( 1593215 )
1992
7
A novel homozygous missense mutation in the protein C (PROC) gene causing recurrent venous thrombosis. ( 1511988 )
1992
8
Late-onset homozygous protein C deficiency. ( 1678832 )
1991
9
A thrombotic state due to an abnormal protein C. ( 3185623 )
1988

Variations for Thrombophilia Due to Protein C Deficiency, Autosomal Recessive

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

76
# Symbol AA change Variation ID SNP ID
1 PROC p.Ala178Pro VAR_006660 rs125425794
2 PROC p.Pro289Leu VAR_006679 rs121918151
3 PROC p.Arg328His VAR_006690
4 PROC p.Gly334Ser VAR_006691 rs121918150
5 PROC p.Val367Ala VAR_006695 rs767730328
6 PROC p.Gly418Asp VAR_006703
7 PROC p.Asp77Gly VAR_073145
8 PROC p.Ala163Glu VAR_073146

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

6 (show all 23)
# Gene Variation Type Significance SNP ID Assembly Location
1 PROC PROC, ARG12TRP undetermined variant Pathogenic
2 PROC NM_000312.3(PROC): c.631C> T (p.Arg211Trp) single nucleotide variant Pathogenic/Likely pathogenic rs121918143 GRCh37 Chromosome 2, 128183756: 128183756
3 PROC NM_000312.3(PROC): c.631C> T (p.Arg211Trp) single nucleotide variant Pathogenic/Likely pathogenic rs121918143 GRCh38 Chromosome 2, 127426180: 127426180
4 PROC NM_000312.3(PROC): c.902C> T (p.Ala301Val) single nucleotide variant Pathogenic rs121918144 GRCh37 Chromosome 2, 128186038: 128186038
5 PROC NM_000312.3(PROC): c.902C> T (p.Ala301Val) single nucleotide variant Pathogenic rs121918144 GRCh38 Chromosome 2, 127428462: 127428462
6 PROC NM_000312.3(PROC): c.629C> T (p.Pro210Leu) single nucleotide variant Pathogenic rs121918145 GRCh37 Chromosome 2, 128183754: 128183754
7 PROC NM_000312.3(PROC): c.629C> T (p.Pro210Leu) single nucleotide variant Pathogenic rs121918145 GRCh38 Chromosome 2, 127426178: 127426178
8 PROC NM_000312.3(PROC): c.925G> A (p.Ala309Thr) single nucleotide variant Pathogenic rs121918146 GRCh37 Chromosome 2, 128186061: 128186061
9 PROC NM_000312.3(PROC): c.925G> A (p.Ala309Thr) single nucleotide variant Pathogenic rs121918146 GRCh38 Chromosome 2, 127428485: 127428485
10 PROC NM_000312.3(PROC): c.1027G> A (p.Gly343Ser) single nucleotide variant Pathogenic rs121918147 GRCh37 Chromosome 2, 128186163: 128186163
11 PROC NM_000312.3(PROC): c.1027G> A (p.Gly343Ser) single nucleotide variant Pathogenic rs121918147 GRCh38 Chromosome 2, 127428587: 127428587
12 PROC NM_000312.3(PROC): c.185A> C (p.Glu62Ala) single nucleotide variant Pathogenic rs121918148 GRCh37 Chromosome 2, 128178973: 128178973
13 PROC NM_000312.3(PROC): c.185A> C (p.Glu62Ala) single nucleotide variant Pathogenic rs121918148 GRCh38 Chromosome 2, 127421397: 127421397
14 PROC NM_000312.3(PROC): c.226G> A (p.Val76Met) single nucleotide variant Pathogenic rs121918149 GRCh37 Chromosome 2, 128179014: 128179014
15 PROC NM_000312.3(PROC): c.226G> A (p.Val76Met) single nucleotide variant Pathogenic rs121918149 GRCh38 Chromosome 2, 127421438: 127421438
16 PROC NM_000312.3(PROC): c.1000G> A (p.Gly334Ser) single nucleotide variant Pathogenic rs121918150 GRCh37 Chromosome 2, 128186136: 128186136
17 PROC NM_000312.3(PROC): c.1000G> A (p.Gly334Ser) single nucleotide variant Pathogenic rs121918150 GRCh38 Chromosome 2, 127428560: 127428560
18 PROC NM_000312.3(PROC): c.866C> T (p.Pro289Leu) single nucleotide variant Pathogenic rs121918151 GRCh37 Chromosome 2, 128186002: 128186002
19 PROC NM_000312.3(PROC): c.866C> T (p.Pro289Leu) single nucleotide variant Pathogenic rs121918151 GRCh38 Chromosome 2, 127428426: 127428426
20 PROC NM_000312.3(PROC): c.793C> T (p.Leu265Phe) single nucleotide variant Pathogenic rs121918156 GRCh37 Chromosome 2, 128184795: 128184795
21 PROC NM_000312.3(PROC): c.793C> T (p.Leu265Phe) single nucleotide variant Pathogenic rs121918156 GRCh38 Chromosome 2, 127427219: 127427219
22 PROC NM_000312.3(PROC): c.1335C> G (p.Ile445Met) single nucleotide variant Pathogenic rs121918157 GRCh37 Chromosome 2, 128186471: 128186471
23 PROC NM_000312.3(PROC): c.1335C> G (p.Ile445Met) single nucleotide variant Pathogenic rs121918157 GRCh38 Chromosome 2, 127428895: 127428895

Expression for Thrombophilia Due to Protein C Deficiency, Autosomal Recessive

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

Pathways for Thrombophilia Due to Protein C Deficiency, Autosomal Recessive

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

Sources for Thrombophilia Due to Protein C Deficiency, Autosomal Recessive

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