F9 coagulation factor IX [Homo sapiens (human)] - Gene

Summary

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Official Symbol: F9provided by HGNC
Official Full Name: coagulation factor IXprovided by HGNC
Primary source: HGNC:3551
Locus tag: RP6-88D7.1
See related: Ensembl:ENSG00000101981; HPRD:02385; MIM:300746; Vega:OTTHUMG00000022536
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FIX; P19; PTC; HEMB; THPH8
Summary: This gene encodes vitamin K-dependent coagulation factor IX that circulates in the blood as an inactive zymogen. This factor is converted to an active form by factor XIa, which excises the activation peptide and thus generates a heavy chain and a light chain held together by one or more disulfide bonds. The role of this activated factor IX in the blood coagulation cascade is to activate factor X to its active form through interactions with Ca+2 ions, membrane phospholipids, and factor VIII. Alterations of this gene, including point mutations, insertions and deletions, cause factor IX deficiency, which is a recessive X-linked disorder, also called hemophilia B or Christmas disease. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: Xq27.1-q27.2

Sequence :: Chromosome: X; NC_000023.10 (138612895..138645617)

See F9 in Epigenomics, MapViewer

Chromosome X - NC_000023.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Results indicate that fXIa activates fIX by an exosite- and Ca(2+)-mediated release-rebind mechanism.
Title: A sequential mechanism for exosite-mediated factor IX activation by factor XIa.
Heme binds to factor VIII and inhibits its interaction with activated factor IX.
Title: Heme binds to factor VIII and inhibits its interaction with activated factor IX.
Western blotting of plasma from FIX deficient (Hemophilia B) patients revealed traces of full-length FIX for the p.R294* and p.R298* mutations, but not for the p.L103* mutation that triggered major FIX mRNA decay.
Title: Ribosome readthrough accounts for secreted full-length factor IX in hemophilia B patients with nonsense mutations.
factor IX mutations were identified in either the exon or intronic regions in haemophilia B patients in Malaysia; one novel mutation, 6660_6664delTTCTT was identified in siblings with moderate form of haemophilia B
Title: Factor IX mutations in haemophilia B patients in Malaysia: a preliminary study.
The F9 mutations were heterogenous and the missense mutations were the most prevalent gene defects in Chinese haemophilia B patients.
Title: Spectrum of F9 mutations in Chinese haemophilia B patients: identification of 20 novel mutations.
The disposition of FIX was well described by a three-compartment PK model.
Title: Population pharmacokinetics of plasma-derived factor IX in adult patients with haemophilia B: implications for dosing in prophylaxis.
Partial reduction of FXIa/S557A to produce heavy and light chains resulted in decreased FIX binding, and this function was regained upon reformation of the disulfide linkage between the heavy and the light chains.
Title: Productive recognition of factor IX by factor XIa exosites requires disulfide linkage between heavy and light chains of factor XIa.
A number of 513 consecutive patients (494-haemophilia A and 19-haemophilia B) from eight haemophilia treatment centers have been investigated with Bethesda assay for the presence of factor VIII or IX inhibitors.
Title: Development of inhibitors in haemophilia. Ongoing epidemiological study.
The authors demonstrate that coagulation factor IX (FIX) efficiently enhances binding and infection by human species A adenoviruses 18 and 31, but not by 12, in epithelial cells originating from the airways or intestine.
Title: Coagulation factor IX mediates serotype-specific binding of species A adenoviruses to host cells.
three novel mutations in factor IX in patients with haemophilia B
Title: FIX mutation spectrum in haemophilia B patients from Jordan: identification of three novel mutations.

Submit: New GeneRIF Correction See all (95)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Hereditary factor IX deficiency disease

MIM: 306900

Genetic Testing Registry

Summary from GeneReviews: Hemophilia B

Hemophilia B is characterized by deficiency in factor IX clotting activity that results in prolonged oozing after injuries, tooth extractions, or surgery, and delayed or recurrent bleeding prior to complete wound healing. The age of diagnosis and frequency of bleeding episodes are related to the level of factor IX clotting activity. In severe hemophilia B, spontaneous joint or deep-muscle bleeding is the most frequent symptom. Individuals with severe hemophilia B are usually diagnosed during the first two years of life; without prophylactic treatment, they may average up to two to five spontaneous bleeding episodes each month. Individuals with moderate hemophilia B seldom have spontaneous bleeding; however, they do have prolonged or delayed oozing after relatively minor trauma and are usually diagnosed before age five to six years; the frequency of bleeding episodes varies from once a month to once a year. Individuals with mild hemophilia B do not have spontaneous bleeding episodes; however, without pre- and post-operative treatment, abnormal bleeding occurs with surgery or tooth extractions; the frequency of bleeding may vary from once a year to once every ten years. Individuals with mild hemophilia B are often not diagnosed until later in life. Other. In any individual with hemophilia B, bleeding episodes may be more frequent in childhood and adolescence than in adulthood. Approximately 10% of carrier females are at risk for bleeding (even if the affected family member has mild hemophilia B) and are thus symptomatic carriers, although symptoms are usually mild. After major trauma or invasive procedures, prolonged or excessive bleeding usually occurs, regardless of severity.

Diagnosis Testing

The diagnosis of hemophilia B is established in individuals with low factor IX clotting activity. Molecular genetic testing of F9, the gene encoding factor IX, identifies disease-causing mutations in more than 99% of individuals with hemophilia B. Such testing is available clinically.

Genetic Counseling

Hemophilia B is inherited in an X-linked manner. The risk to sibs of a proband depends on the carrier status of the mother. Carrier females have a 50% chance of transmitting the F9 mutation in each pregnancy. Sons who inherit the mutation will be affected; daughters who inherit the mutation are carriers. Affected males transmit the mutation to all of their daughters and none of their sons. Carrier testing for family members at risk and prenatal testing for pregnancies at increased risk are possible if the F9 disease-causing mutation has been identified in a family member or if informative intragenic, linked markers have been identified.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P00740	P00734	F2	HPRD	PubMed
P00740	P08709	F7	HPRD	PubMed
P00740	P00451	F8	HPRD	PubMed
P00740	P38435	GGCX	HPRD	PubMed
P00740	Q07954	LRP1	HPRD	PubMed
BioGRID:108456	BioGRID:110215	LRP1	BioGRID	PubMed	Reconstituted Complex

Pathways from BioSystems

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Blood Clotting Cascade, organism-specific biosystem (from WikiPathways)
Blood Clotting Cascade, organism-specific biosystemCoagulation is a complex process by which blood forms clots. It is an important part of hemostasis (the cessation of blood loss from a damaged vessel), wherein a damaged blood vessel wall is covered ...
Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
Complement and coagulation cascades, organism-specific biosystem (from KEGG)
Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
Complement and coagulation cascades, conserved biosystem (from KEGG)
Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
Extrinsic Pathway, organism-specific biosystem (from REACTOME)
Extrinsic Pathway, organism-specific biosystemFactor VII, the protease that initiates the normal blood clotting cascade, circulates in the blood in both its proenzyme (factor VII) and its activated (factor VIIa) forms. No clotting occurs, howev...
Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystem (from REACTOME)
Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystemThe formation of a fibrin clot at the site of an injury to the wall of a normal blood vessel is an essential part of the process to stop blood loss after vascular injury. The reactions that lead to ...
Gamma-carboxylation of protein precursors, organism-specific biosystem (from REACTOME)
Gamma-carboxylation of protein precursors, organism-specific biosystemGamma-carboxylation of a cluster of glutamate residues near the amino termini of thrombin, factor VII, factor IX, factor X, protein C, protein S, protein Z, and Gas 6 is required for these proteins t...
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins, organism-specific biosystem (from REACTOME)
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins, organism-specific biosystemA number of proteins, including eight required for normal blood clot formation and its regulation (Prothrombin (factor II), factor VII, factor IX, factor X, protein C, protein S, protein Z, and Gas6)...
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
Intrinsic Pathway, organism-specific biosystem (from REACTOME)
Intrinsic Pathway, organism-specific biosystemThe intrinsic pathway of blood clotting connects interactions among kininogen (high molecular weight kininogen, HK), prekallikrein (PK), and factor XII to the activation of clotting factor X by a ser...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
PTM: gamma carboxylation, hypusine formation and arylsulfatase activation, organism-specific biosystem (from REACTOME)
PTM: gamma carboxylation, hypusine formation and arylsulfatase activation, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
Post-translational protein modification, organism-specific biosystem (from REACTOME)
Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
Removal of aminoterminal propeptides from gamma-carboxylated proteins, organism-specific biosystem (from REACTOME)
Removal of aminoterminal propeptides from gamma-carboxylated proteins, organism-specific biosystemFurin is an endopeptidase localized to the Golgi membrane that cleaves many proteins on the carboxyterminal side of the sequence motif Arg-[any residue]-(Lys or Arg)-Arg (Jones et al. 1995; Leduc et ...
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus, organism-specific biosystem (from REACTOME)
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus, organism-specific biosystemThe details of the vesicle-mediated transport of proteins from the endoplasmic reticulum to the Golgi apparatus will be annotated in a future release of Reactome.

General gene information

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Markers

GDB:197038 (e-PCR)
- UniSTS:155919

GDB:197039 (e-PCR)
- UniSTS:155920

G28615 (e-PCR)
- UniSTS:56096

GDB:177588 (e-PCR)
- UniSTS:154932

GDB:177796 (e-PCR)
- UniSTS:154962

F9 (e-PCR), detects polymorphism
- UniSTS:525911

GDB:177926 (e-PCR)
- UniSTS:154982

RH17659 (e-PCR)
- UniSTS:22655

GDB:178640 (e-PCR)
- UniSTS:155035

G66627 (e-PCR)
- UniSTS:166822

G66628 (e-PCR)
- UniSTS:166823

G66629 (e-PCR)
- UniSTS:166824

F9 (e-PCR), detects polymorphism
- UniSTS:266922

GDB:181635 (e-PCR)
- UniSTS:155321

GDB:181846 (e-PCR)
- UniSTS:155334

GDB:182120 (e-PCR)
- UniSTS:155347

GDB:182121 (e-PCR)
- UniSTS:155348

GDB:182122 (e-PCR)
- UniSTS:155349

F9_627 (e-PCR)
- UniSTS:277225

F9_V31 (e-PCR)
- UniSTS:277225

G10618 (e-PCR)
- UniSTS:21481

GDB:303850 (e-PCR)
- UniSTS:156398

GDB:192503 (e-PCR)
- UniSTS:99325

Genotypes

See F9 SNP Geneview Report
See F9 SNP Genotype Report
See F9 SNP Variation Viewer Report

Homology

Homologs of the F9 gene: The F9 gene is conserved in chimpanzee, Rhesus monkey, dog, mouse, chicken, zebrafish, fruit fly, and mosquito.
Map Viewer (Mouse)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

MGC129641, MGC129642

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
calcium ion binding	IEA Inferred from Electronic Annotation more info
serine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
blood coagulation	TAS Traceable Author Statement more info
blood coagulation, extrinsic pathway	TAS Traceable Author Statement more info
blood coagulation, intrinsic pathway	TAS Traceable Author Statement more info
cellular protein metabolic process	TAS Traceable Author Statement more info
peptidyl-glutamic acid carboxylation	TAS Traceable Author Statement more info
post-translational protein modification	TAS Traceable Author Statement more info
proteolysis	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
Golgi lumen	TAS Traceable Author Statement more info
endoplasmic reticulum lumen	TAS Traceable Author Statement more info
extracellular region	NAS Non-traceable Author Statement more info	PubMed
extracellular region	TAS Traceable Author Statement more info
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: coagulation factor IX

Names: coagulation factor IX; F9 p22; FIX F9; factor 9; factor IX F9; Christmas factor; plasma thromboplastic component; plasma thromboplastin component

NP_000124.1

EC 3.4.21.22

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007994.1 RefSeqGene

Range

5001..37723

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000133.3 → NP_000124.1 coagulation factor IX preproprotein

Status: REVIEWED

Source sequence(s)

AL033403, BC109214, M11309

Consensus CDS

CCDS14666.1

UniProtKB/Swiss-Prot

P00740

Related

ENSP00000218099, OTTHUMP00000024154, ENST00000218099, OTTHUMT00000058557

Conserved Domains (4) summary

cd00054
Location:93 – 129
Blast Score: 124

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00190
Location:227 – 457
Blast Score: 676

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

smart00069
Location:28 – 92
Blast Score: 261

GLA; Domain containing Gla (gamma-carboxyglutamate) residues.

cl00057
Location:123 – 169
Blast Score: 88

vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000023.10 Reference GRCh37.p10 Primary Assembly

Range

138612895..138645617

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000155.1 Alternate HuRef

Range

127880671..127913025

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018934.1 Alternate CHM1_1.0

Range

138570075..138602799

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	A01819.1	CAA00205.1
genomic	A07407.1	CAA00665.1
genomic	A14017.1	CAA01141.1
genomic	ABBA01066041.1 (425..3194)	None
genomic	ABBA01066042.1	None
genomic	ABBA01066043.1	None
genomic	ABBA01066044.1	None
genomic	ABBA01066045.1	None
genomic	ABBA01066046.1 (3583..4042)	None
genomic	AF486577.1	None
genomic	AF536327.1	AAM96188.1
genomic	AL033403.1 (4055..36777)	None
genomic	AL645665.11	None
genomic	AMYH01023058.1 (7410..40134)	None
genomic	AY226143.1	AAO73937.1
genomic	AY269424.1	AAP34372.1
genomic	AY269425.1	AAP34373.1
genomic	CH471150.2	EAW88431.1
		EAW88432.1
		EAW88433.1
		EAW88434.1
genomic	CS355175.1	CAL24229.1
genomic	DQ431774.1	ABF68963.1
genomic	DQ431775.1	ABF68964.1
genomic	DQ431776.1	ABF68965.1
genomic	DQ431777.1	ABF68966.1
genomic	DQ431778.1	ABF68967.1
genomic	DQ431779.1	ABF68968.1
genomic	DQ431780.1	ABF68969.1
genomic	DQ431781.1	ABF68970.1
genomic	DQ431782.1	ABF68971.1
genomic	DQ431783.1	ABF68972.1
genomic	DQ431784.1	ABF68973.1
genomic	DQ431785.1	ABF68974.1
genomic	DQ431786.1	ABF68975.1
genomic	DQ431787.1	ABF68976.1
genomic	DQ431788.1	ABF68977.1
genomic	DQ431789.1	ABF68978.1
genomic	DQ431790.1	ABF68979.1
genomic	DQ431791.1	ABF68980.1
genomic	DQ431792.1	ABF68981.1
genomic	DQ431793.1	ABF68982.1
genomic	DQ431795.1	ABF68984.1
genomic	DQ431796.1	ABF68985.1
genomic	DQ431797.1	ABF68986.1
genomic	DQ431798.1	ABF68987.1
genomic	DQ431801.1	ABF68990.1
genomic	DQ431802.1	ABF68991.1
genomic	DQ431803.1	ABF68992.1
genomic	DQ431804.1	ABF68993.1
genomic	DQ431805.1	ABF68994.1
genomic	DQ431806.1	ABF68995.1
genomic	DQ431807.1	ABF68996.1
genomic	DQ431808.1	ABF68997.1
genomic	DQ431809.1	ABF68998.1
genomic	DQ431810.1	ABF68999.1
genomic	DQ431811.1	ABF69000.1
genomic	DQ431812.1	ABF69001.1
genomic	DQ431813.1	ABF69002.1
genomic	DQ431814.1	ABF69003.1
genomic	DQ431815.1	ABF69004.1
genomic	DQ431816.1	ABF69005.1
genomic	DQ431817.1	ABF69006.1
genomic	DQ431818.1	ABF69007.1
genomic	DQ431819.1	ABF69008.1
genomic	DQ431820.1	ABF69009.1
genomic	DQ431821.1	ABF69010.1
genomic	DQ431822.1	ABF69011.1
genomic	DQ431823.1	ABF69012.1
genomic	DQ431824.1	ABF69013.1
genomic	DQ431825.1	ABF69014.1
genomic	DQ431826.1	ABF69015.1
genomic	DQ431827.1	ABF69016.1
genomic	DQ431828.1	ABF69017.1
genomic	DQ431829.1	ABF69018.1
genomic	DQ431830.1	ABF69019.1
genomic	DQ431831.1	ABF69020.1
genomic	DQ431832.1	ABF69021.1
genomic	DQ431833.1	ABF69022.1
genomic	DQ431834.1	ABF69023.1
genomic	DQ431835.1	ABF69024.1
genomic	DQ431836.1	ABF69025.1
genomic	DQ431837.1	ABF69026.1
genomic	DQ431838.1	ABF69027.1
genomic	DQ431839.1	ABF69028.1
genomic	DQ431840.1	ABF69029.1
genomic	K02053.1	AAA56822.1
genomic	K02402.1	AAB59620.1
genomic	M19063.1	AAA52456.1
genomic	S66752.1	AAB28588.1
genomic	S68634.1	AAB29758.1
genomic	X55008.1	CAB38245.2
mRNA	AB186358.1	BAD89383.1
mRNA	AK292749.1	BAF85438.1
mRNA	BC109214.1	AAI09215.1
mRNA	BC109215.1	AAI09216.1
mRNA	FR846238.1	CCA61110.1
mRNA	FR846239.1	CCA61111.1
mRNA	FR846240.1	CCA61112.1
mRNA	J00136.1	AAA98726.1
mRNA	J00137.1	AAA52763.1
mRNA	M11309.1	AAA52023.1
mRNA	M35672.1	AAA51981.1
mRNA	A13997.1	CAA01140.1
other-genetic	BC146406.1	AAI46407.1