F9

Protein identityUniProt · HPA

UniProt accession

P00740

Gene

F9

Ensembl

ENSG00000101981

Chromosome

X

Canonical length

461 aa

Protein class

Candidate cardiovascular disease genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

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. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Sep 2015]

Canonical amino-acid sequenceUniProt

461 residues, UniProt reviewed canonical sequence.

>P00740|F9
     1  MQRVNMIMAE SPGLITICLL GYLLSAECTV FLDHENANKI LNRPKRYNSG KLEEFVQGNL
    61  ERECMEEKCS FEEAREVFEN TERTTEFWKQ YVDGDQCESN PCLNGGSCKD DINSYECWCP
   121  FGFEGKNCEL DVTCNIKNGR CEQFCKNSAD NKVVCSCTEG YRLAENQKSC EPAVPFPCGR
   181  VSVSQTSKLT RAETVFPDVD YVNSTEAETI LDNITQSTQS FNDFTRVVGG EDAKPGQFPW
   241  QVVLNGKVDA FCGGSIVNEK WIVTAAHCVE TGVKITVVAG EHNIEETEHT EQKRNVIRII
   301  PHHNYNAAIN KYNHDIALLE LDEPLVLNSY VTPICIADKE YTNIFLKFGS GYVSGWGRVF
   361  HKGRSALVLQ YLRVPLVDRA TCLRSTKFTI YNNMFCAGFH EGGRDSCQGD SGGPHVTEVE
   421  GTSFLTGIIS WGEECAMKGK YGIYTKVSRY VNWIKEKTKL T

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against F9 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

659 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about F9.

Disease | AllUniProt

Conditions F9 is implicated in, by any mechanism.

• Hemophilia B (HEMB) MIM:306900
• Thrombophilia, X-linked, due to factor IX defect (THPH8) MIM:300807
• Warfarin sensitivity, X-linked (WARFS) MIM:301052

Disease | GeneticClinVar

313 pathogenic / likely-pathogenic of 681 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary factor IX deficiency disease
• Thrombophilia, X-linked, due to factor 9 defect
• Hereditary factor VIII deficiency disease
• F9-related disorder
• Warfarin sensitivity, X-linked

Disease | AutoantibodyPubMed

Conditions in which antibodies against F9 are reported. Each links to that disease's full target list.

Showing 0 of 2 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for F9 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.17

gnomAD pLI

1

gnomAD missense Z

2.18

DepMap mean gene effect

-0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood coagulation
• proteolysis
• zymogen activation

Molecular functions

• calcium ion binding
• endopeptidase activity
• metal ion binding
• serine-type endopeptidase activity

Cellular components

• endoplasmic reticulum lumen
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• Golgi lumen
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• Gamma-carboxyglutamic acid-rich (GLA) domain
• EGF-like domain
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• EGF-like calcium-binding domain
• Peptidase S1, PA clan
• Peptidase S1A, coagulation factor VII/IX/X/C/Z
• Coagulation factor-like, Gla domain superfamily
• EGF-like calcium-binding, conserved site
• Serine proteases, trypsin family, histidine active site
• Serine proteases, trypsin family, serine active site
• Gamma-carboxyglutamic acid-rich (GLA) domain superfamily
• Peptidase S1 family, coagulation factors
• EGF-like domain
• Trypsin
• Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain
• Coagulation Factor Xa inhibitory site

KeywordsUniProt

• Blood coagulation
• Calcium
• Cleavage on pair of basic residues
• Disulfide bond
• EGF-like domain
• Gamma-carboxyglutamic acid
• Glycoprotein
• Hemophilia
• Hemostasis
• Hydrolase
• Hydroxylation
• Magnesium
• Metal-binding
• Pharmaceutical
• Phosphoprotein
• Protease
• Repeat
• Secreted
• Serine protease
• Signal
• Sulfation
• Thrombophilia
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of F9 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SERPINC1