Thrombophilia, X-Linked, Due to Factor Ix Defect (THPH8)

Categories: Blood diseases, Genetic diseases

Aliases & Classifications for Thrombophilia, X-Linked, Due to Factor Ix Defect

MalaCards integrated aliases for Thrombophilia, X-Linked, Due to Factor Ix Defect:

Name: Thrombophilia, X-Linked, Due to Factor Ix Defect 57 72 29 13 6 44 39 70
Deep Venous Thrombosis, Protection Against 57 29 6
Thph8 57 12 72
X-Linked Thrombophilia Due to Factor Ix Defect 12 15



57 (Updated 05-Apr-2021)
x-linked recessive

based on report of 1 family (last curated july 2020)


thrombophilia, x-linked, due to factor ix defect:
Inheritance x-linked recessive inheritance


External Ids:

Disease Ontology 12 DOID:0111899
OMIM® 57 300807
OMIM Phenotypic Series 57 PS188050
SNOMED-CT via HPO 68 128053003 234467004 76612001
UMLS 70 C2749016

Summaries for Thrombophilia, X-Linked, Due to Factor Ix Defect

Disease Ontology : 12 A thrombophilia characterized by normal levels of F9 antigen, but very high levels of F9 activity that has material basis in hemizygous gain of function mutation in F9 on chromosome Xq27.1.

MalaCards based summary : Thrombophilia, X-Linked, Due to Factor Ix Defect, is also known as deep venous thrombosis, protection against. An important gene associated with Thrombophilia, X-Linked, Due to Factor Ix Defect is F9 (Coagulation Factor IX). Related phenotypes are deep venous thrombosis and increased factor ix activity

UniProtKB/Swiss-Prot : 72 Thrombophilia, X-linked, due to factor IX defect: A hemostatic disorder characterized by a tendency to thrombosis.

More information from OMIM: 300807 PS188050

Related Diseases for Thrombophilia, X-Linked, Due to Factor Ix Defect

Symptoms & Phenotypes for Thrombophilia, X-Linked, Due to Factor Ix Defect

Human phenotypes related to Thrombophilia, X-Linked, Due to Factor Ix Defect:

# Description HPO Frequency HPO Source Accession
1 deep venous thrombosis 31 very rare (1%) HP:0002625
2 increased factor ix activity 31 very rare (1%) HP:0033061
3 hypercoagulability 31 HP:0100724

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Laboratory Abnormalities:
increased factor ix activity

deep vein thrombosis

Clinical features from OMIM®:

300807 (Updated 05-Apr-2021)

Drugs & Therapeutics for Thrombophilia, X-Linked, Due to Factor Ix Defect

Search Clinical Trials , NIH Clinical Center for Thrombophilia, X-Linked, Due to Factor Ix Defect

Cochrane evidence based reviews: thrombophilia, x-linked, due to factor ix defect

Genetic Tests for Thrombophilia, X-Linked, Due to Factor Ix Defect

Genetic tests related to Thrombophilia, X-Linked, Due to Factor Ix Defect:

# Genetic test Affiliating Genes
1 Thrombophilia, X-Linked, Due to Factor Ix Defect 29 F9
2 Deep Venous Thrombosis, Protection Against 29

Anatomical Context for Thrombophilia, X-Linked, Due to Factor Ix Defect

Publications for Thrombophilia, X-Linked, Due to Factor Ix Defect

Articles related to Thrombophilia, X-Linked, Due to Factor Ix Defect:

(show top 50) (show all 54)
# Title Authors PMID Year
X-linked thrombophilia with a mutant factor IX (factor IX Padua). 6 57
19846852 2009
F9 Malmö, factor IX and deep vein thrombosis. 6 57
19286883 2009
The chaperone-like sodium phenylbutyrate improves factor IX intracellular trafficking and activity impaired by the frequent p.R294Q mutation. 6
29993188 2018
Advanced cell-based modeling of the royal disease: characterization of the mutated F9 mRNA. 6
28834196 2017
First case report of hemophilia B Leyden in Japan. 6
28168417 2017
Combined coagulation factor VIII and factor IX deficiency (CDF8F9) in a patient from Lithuania. 6
27824213 2016
Mutation analysis of Swedish haemophilia B families - high frequency of unique mutations. 6
26612714 2016
[Mutational Analysis of Hemophilia B in Russia: Molecular-Genetic Study]. 6
27529981 2016
Genetic determinants of immunogenicity to factor IX during the treatment of haemophilia B. 6
25470321 2015
Mutation analysis of a cohort of US patients with hemophilia B. 6
24375831 2014
A CpG mutational hotspot in a ONECUT binding site accounts for the prevalent variant of hemophilia B Leyden. 6
23472758 2013
Assessment of the F9 genotype-specific FIX inhibitor risks and characterisation of 10 novel severe F9 defects in the first molecular series of Argentinian patients with haemophilia B. 6
23093250 2013
Analysis of F9 point mutations and their correlation to severity of haemophilia B disease. 6
22639855 2012
Spectrum of F9 mutations in Chinese haemophilia B patients: identification of 20 novel mutations. 6
22544209 2012
F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity. 6
22103590 2012
Hemophilia B is a quasi-quantitative condition with certain mutations showing phenotypic plasticity. 6
19699296 2009
Genotype analysis identifies the cause of the "royal disease". 6
19815722 2009
Sequence variants and haplotypes of the factor IX gene and the risk of venous thrombosis. 57
18624978 2008
Identification of mutations in the F9 gene including exon deletion by multiplex ligation-dependent probe amplification in 33 unrelated Korean patients with haemophilia B. 6
18624698 2008
Gene variants associated with deep vein thrombosis. 57
18349091 2008
Molecular pathology of haemophilia B: identification of five novel mutations including a LINE 1 insertion in Indian patients. 6
15086324 2004
Factor IX gene sequencing by a simple and sensitive 15-hour procedure for haemophilia B diagnosis: identification of two novel mutations. 6
11122099 2000
Hemophilia B 6
20301668 2000
High levels of factor IX increase the risk of venous thrombosis. 57
10845896 2000
Fast and efficient mutation detection method using multiplex PCR and cycle sequencing--application to haemophilia B. 6
10739381 2000
Factor IX gene analysis in 70 unrelated patients with haemophilia B: description of 13 new mutations. 6
10595634 1999
Changing residue 338 in human factor IX from arginine to alanine causes an increase in catalytic activity. 57
9575152 1998
A Gly --> Ser change causes defective folding in vitro of calcium-binding epidermal growth factor-like domains from factor IX and fibrillin-1. 6
9525872 1998
Germline mutations in Peruvian patients with hemophilia B: pattern of mutation in AmerIndians is similar to the putative endogenous germline pattern. 6
9600455 1998
Factor IX gene mutations in haemophilia B: a New Zealand population-based study. 6
27213901 1996
Haemophilia B (sixth edition): a database of point mutations and short additions and deletions. 6
8594556 1996
The high frequency of the -6G-->A factor IX promoter mutation is the result both of a founder effect and recurrent mutation at a CpG dinucleotide. 6
7734378 1995
Twenty-five novel mutations of the factor IX gene in haemophilia B. 6
8680410 1995
Haemophilia B: database of point mutations and short additions and deletions, fifth edition, 1994. 6
7937052 1994
Moderate hemophilia B Leyden: identification by polymerase chain reaction, sequencing, and oligomer restriction. 6
7677806 1994
First report on UK database of haemophilia B mutations and pedigrees. UK Haemophilia Centres. 6
8091381 1994
The rates and patterns of deletions in the human factor IX gene. 6
8304338 1994
Haemophilia B Liverpool: a new British family with mild haemophilia B associated with a -6 G to A mutation in the factor IX promoter. 6
8251390 1993
Detection of a molecular defect in 40 of 44 patients with haemophilia B by PCR and denaturing gradient gel electrophoresis. 6
8217825 1993
The pattern of spontaneous germ-line mutation: relative rates of mutation at or near CpG dinucleotides in the factor IX gene. 6
8314564 1993
Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation. 6
8434583 1993
T296----M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection. 6
1864609 1991
CG dinucleotide transitions in the factor IX gene account for about half of the point mutations in hemophilia B patients: a Seattle series. 6
2066105 1991
Point mutations in four hemophilia B patients from China. 6
2270538 1990
Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene. 6
2198809 1990
Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden. 6
2352926 1990
Recurrent nonsense mutations at arginine residues cause severe hemophilia B in unrelated hemophiliacs. 6
1969838 1990
Three point mutations in the factor IX genes of five hemophilia B patients. Identification strategy using localization by altered epitopes in their hemophilic proteins. 6
2472424 1989
Identification of a single nucleotide C-to-T transition and five different deletions in patients with severe hemophilia B. 6
2741941 1989
Detection of polymorphisms at cytosine phosphoguanadine dinucleotides and diagnosis of haemophilia B carriers. 6
2564457 1989

Variations for Thrombophilia, X-Linked, Due to Factor Ix Defect

ClinVar genetic disease variations for Thrombophilia, X-Linked, Due to Factor Ix Defect:

6 (show top 50) (show all 57)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 F9 NM_000133.3(F9):c.580A>G (p.Thr194Ala) SNV protective 10588 rs6048 GRCh37: X:138633280-138633280
GRCh38: X:139551121-139551121
2 F9 NM_000133.3(F9):c.1151G>T (p.Arg384Leu) SNV Pathogenic 10668 rs137852283 GRCh37: X:138643995-138643995
GRCh38: X:139561836-139561836
3 F9 NM_000133.3(F9):c.223C>T (p.Arg75Ter) SNV Pathogenic 10572 rs137852227 GRCh37: X:138619303-138619303
GRCh38: X:139537144-139537144
4 F9 NC_000023.11:g.(?_139541049)_(139563439_?)del Deletion Pathogenic 830844 GRCh37: X:138623208-138645598
5 F9 NC_000023.11:g.(?_139530759)_(139562076_?)del Deletion Pathogenic 537740 GRCh37: X:138612918-138644235
GRCh38: X:139530759-139562076
6 F9 NM_000133.3(F9):c.253-1G>C SNV Pathogenic 574429 rs1434866164 GRCh37: X:138619520-138619520
GRCh38: X:139537361-139537361
7 F9 NM_000133.3(F9):c.1025C>T (p.Thr342Met) SNV Pathogenic 10607 rs137852254 GRCh37: X:138643869-138643869
GRCh38: X:139561710-139561710
8 F9 NM_000133.3(F9):c.-35G>A SNV Pathogenic 641767 rs1166164399 GRCh37: X:138612889-138612889
GRCh38: X:139530730-139530730
9 F9 NM_000133.3(F9):c.316G>A (p.Gly106Ser) SNV Pathogenic 10579 rs137852233 GRCh37: X:138623273-138623273
GRCh38: X:139541114-139541114
10 F9 NM_000133.3(F9):c.88G>A (p.Val30Ile) SNV Pathogenic 651569 rs1603263395 GRCh37: X:138613011-138613011
GRCh38: X:139530852-139530852
11 F9 NM_000133.3(F9):c.881G>A (p.Arg294Gln) SNV Pathogenic 10602 rs137852249 GRCh37: X:138643725-138643725
GRCh38: X:139561566-139561566
12 F9 NC_000023.11:g.(?_139530701)_(139563439_?)del Deletion Pathogenic 658437 GRCh37: X:138612860-138645598
GRCh38: X:139530701-139563439
13 overlap with 5 genes NC_000023.10:g.(?_138612860)_(139587225_?)del Deletion Pathogenic 665638 GRCh37: X:138612860-139587225
14 F9 NM_000133.3(F9):c.1150C>T (p.Arg384Ter) SNV Pathogenic 10615 rs137852261 GRCh37: X:138643994-138643994
GRCh38: X:139561835-139561835
15 F9 NM_000133.4(F9):c.545_546del (p.Ser182fs) Deletion Pathogenic 862249 GRCh37: X:138633244-138633245
GRCh38: X:139551085-139551086
16 F9 NM_000133.3(F9):c.880C>T (p.Arg294Ter) SNV Pathogenic 10587 rs137852248 GRCh37: X:138643724-138643724
GRCh38: X:139561565-139561565
17 F9 NM_000133.3(F9):c.278-3A>G SNV Pathogenic 92225 rs398122990 GRCh37: X:138623232-138623232
GRCh38: X:139541073-139541073
18 F9 NM_000133.4(F9):c.482A>G (p.Tyr161Cys) SNV Likely pathogenic 963994 GRCh37: X:138630612-138630612
GRCh38: X:139548453-139548453
19 F9 NM_000133.3(F9):c.148G>A (p.Gly50Ser) SNV Likely pathogenic 454495 rs1556435940 GRCh37: X:138619228-138619228
GRCh38: X:139537069-139537069
20 F9 NM_000133.4(F9):c.1295G>C (p.Gly432Ala) SNV Likely pathogenic 837906 GRCh37: X:138644139-138644139
GRCh38: X:139561980-139561980
21 F9 NM_000133.4(F9):c.1255G>A (p.Val419Met) SNV Uncertain significance 835343 GRCh37: X:138644099-138644099
GRCh38: X:139561940-139561940
22 F9 NM_000133.4(F9):c.364G>A (p.Gly122Arg) SNV Uncertain significance 1026859 GRCh37: X:138623321-138623321
GRCh38: X:139541162-139541162
23 F9 NM_000133.4(F9):c.44T>A (p.Ile15Asn) SNV Uncertain significance 934532 GRCh37: X:138612967-138612967
GRCh38: X:139530808-139530808
24 F9 NM_000133.4(F9):c.1276A>C (p.Thr426Pro) SNV Uncertain significance 1039443 GRCh37: X:138644120-138644120
GRCh38: X:139561961-139561961
25 F9 NM_000133.4(F9):c.855G>C (p.Glu285Asp) SNV Uncertain significance 828138 rs1603267310 GRCh37: X:138643699-138643699
GRCh38: X:139561540-139561540
26 F9 NM_000133.3(F9):c.1148T>C (p.Leu383Pro) SNV Uncertain significance 573753 rs1387119011 GRCh37: X:138643992-138643992
GRCh38: X:139561833-139561833
27 F9 NM_000133.3(F9):c.960A>C (p.Glu320Asp) SNV Uncertain significance 650843 rs1489951549 GRCh37: X:138643804-138643804
GRCh38: X:139561645-139561645
28 F9 NM_000133.4(F9):c.122T>G (p.Leu41Arg) SNV Uncertain significance 834544 GRCh37: X:138619202-138619202
GRCh38: X:139537043-139537043
29 F9 NC_000023.11:g.139530731A>G SNV Uncertain significance 847127 GRCh37: X:138612890-138612890
GRCh38: X:139530731-139530731
30 F9 NM_000133.4(F9):c.250A>G (p.Thr84Ala) SNV Likely benign 695975 rs201120367 GRCh37: X:138619330-138619330
GRCh38: X:139537171-139537171
31 F9 NM_000133.4(F9):c.9C>T (p.Arg3=) SNV Likely benign 799804 rs1335753805 GRCh37: X:138612932-138612932
GRCh38: X:139530773-139530773
32 F9 NM_000133.4(F9):c.60A>G (p.Leu20=) SNV Likely benign 701352 rs762082146 GRCh37: X:138612983-138612983
GRCh38: X:139530824-139530824
33 F9 NM_000133.4(F9):c.1029C>T (p.Asn343=) SNV Likely benign 700040 rs145026483 GRCh37: X:138643873-138643873
GRCh38: X:139561714-139561714
34 F9 NM_000133.4(F9):c.768C>T (p.Ile256=) SNV Benign 751745 rs758909063 GRCh37: X:138642944-138642944
GRCh38: X:139560785-139560785
35 F9 NM_000133.4(F9):c.333C>T (p.Asp111=) SNV Benign 764284 rs139289585 GRCh37: X:138623290-138623290
GRCh38: X:139541131-139541131
36 F9 NM_000133.4(F9):c.7C>T (p.Arg3Cys) SNV Benign 765903 rs766259893 GRCh37: X:138612930-138612930
GRCh38: X:139530771-139530771
37 F9 NM_000133.4(F9):c.507C>G (p.Ser169=) SNV Benign 794265 rs565055999 GRCh37: X:138630637-138630637
GRCh38: X:139548478-139548478
38 F9 NM_000133.3(F9):c.1381A>C (p.Thr461Pro) SNV Benign 368004 rs4149751 GRCh37: X:138644225-138644225
GRCh38: X:139562066-139562066
39 F9 NM_000133.3(F9):c.391+7A>G SNV Benign 367999 rs6049 GRCh37: X:138623355-138623355
GRCh38: X:139541196-139541196
40 F9 NM_000133.3(F9):c.658T>A (p.Ser220Thr) SNV Benign 368001 rs777361659 GRCh37: X:138633358-138633358
GRCh38: X:139551199-139551199
41 F9 NM_000133.4(F9):c.1257G>T (p.Val419=) SNV Benign 696202 rs61731481 GRCh37: X:138644101-138644101
GRCh38: X:139561942-139561942
42 F9 NM_000133.3(F9):c.769G>A (p.Val257Ile) SNV Benign 225354 rs200608775 GRCh37: X:138642945-138642945
GRCh38: X:139560786-139560786
43 F9 NM_000133.4(F9):c.696T>C (p.Asp232=) SNV Benign 697096 rs140835723 GRCh37: X:138633396-138633396
GRCh38: X:139551237-139551237
44 F9 NM_000133.4(F9):c.51C>T (p.Ile17=) SNV Benign 697610 rs774612303 GRCh37: X:138612974-138612974
GRCh38: X:139530815-139530815
45 F9 NM_000133.3(F9):c.108C>T (p.Asn36=) SNV Benign 367998 rs184837275 GRCh37: X:138619188-138619188
GRCh38: X:139537029-139537029
46 F9 NM_000133.4(F9):c.1385A>G (p.Ter462=) SNV Benign 698247 rs561793582 GRCh37: X:138644229-138644229
GRCh38: X:139562070-139562070
47 F9 NM_000133.4(F9):c.730T>C (p.Leu244=) SNV Benign 699709 rs765470577 GRCh37: X:138642906-138642906
GRCh38: X:139560747-139560747
48 F9 NM_000133.4(F9):c.523C>T (p.Pro175Ser) SNV Benign 700019 rs762986355 GRCh37: X:138633223-138633223
GRCh38: X:139551064-139551064
49 F9 NM_000133.3(F9):c.19A>T (p.Ile7Phe) SNV Benign 367997 rs150190385 GRCh37: X:138612942-138612942
GRCh38: X:139530783-139530783
50 F9 NM_000133.3(F9):c.907C>T (p.His303Tyr) SNV Benign 10641 rs1801202 GRCh37: X:138643751-138643751
GRCh38: X:139561592-139561592

UniProtKB/Swiss-Prot genetic disease variations for Thrombophilia, X-Linked, Due to Factor Ix Defect:

# Symbol AA change Variation ID SNP ID
1 F9 p.Arg384Leu VAR_062999 rs137852283

Expression for Thrombophilia, X-Linked, Due to Factor Ix Defect

Search GEO for disease gene expression data for Thrombophilia, X-Linked, Due to Factor Ix Defect.

Pathways for Thrombophilia, X-Linked, Due to Factor Ix Defect

GO Terms for Thrombophilia, X-Linked, Due to Factor Ix Defect

Cellular components related to Thrombophilia, X-Linked, Due to Factor Ix Defect according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 collagen-containing extracellular matrix GO:0062023 8.96 VWA1 F9
2 endoplasmic reticulum lumen GO:0005788 8.62 VWA1 F9

Sources for Thrombophilia, X-Linked, Due to Factor Ix Defect

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
69 Tocris
71 UMLS via Orphanet
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