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CFHR4 Gene

protein-coding   GIFtS: 49
GCID: GC01P196857

Complement Factor H-Related 4


(Previous symbol: CFHL4)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Complement Factor H-Related 41 2
CFHL41 2 3 5
FHR42 3 5
FHR-42 3
Complement Factor H Related 41
Complement Factor H-Related Protein 42

External Ids:    HGNC: 169791   Entrez Gene: 108772   Ensembl: ENSG000001343657   OMIM: 6053375   UniProtKB: Q924963   

Export aliases for CFHR4 gene to outside databases

Previous GC identifers: GC01P195010 GC01P195123 GC01P168014


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CFHR4 Gene:
This gene is a member of the complement factor H (CFH) gene family, and encodes one of the 5 CFH-related (CFHR)
proteins. These 5 genes are closely linked to the CFH gene on chromosome 1q31-q32. The CFHRs are secreted plasma
proteins synthesized primarily by the hepatocytes, and composed of highly-related short consensus repeats (SCRs).
This protein enhances the cofactor activity of CFH, and is involved in complement regulation. It can associate
with lipoproteins and may play a role in lipid metabolism. Alternatively spliced transcript variants encoding
different isoforms (varying in the number of SCRs) have been described for this gene. (provided by RefSeq, Jan
2011)

GeneCards Summary for CFHR4 Gene:
CFHR4 (complement factor H-related 4) is a protein-coding gene. Diseases associated with CFHR4 include kuhnt-junius degeneration, and atypical hemolytic-uremic syndrome. GO annotations related to this gene include lipid transporter activity. An important paralog of this gene is F13B.

UniProtKB/Swiss-Prot: FHR4_HUMAN, Q92496
Function: Involved in complement regulation. Can associate with lipoproteins and may play a role in lipid
metabolism

Gene Wiki entry for CFHR4 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Search for regulatory transcription factor binding sites for CFHR4
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): CFHR4 promoter sequence
   Search Chromatin IP Primers for CFHR4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CFHR4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1q32   Ensembl cytogenetic band:  1q31.3   HGNC cytogenetic band: 1q32

CFHR4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CFHR4 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01P196857:  view genomic region     (about GC identifiers)

Start:
196,819,371 bp from pter      End:
196,888,102 bp from pter
Size:
68,732 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: FHR4_HUMAN, Q92496 (See protein sequence)
Recommended Name: Complement factor H-related protein 4 precursor  
Size: 578 amino acids; 65351 Da
Subunit: Homodimer
Secondary accessions: A8K9N7 B1ALQ9 C9J7J7 Q5DVJ7 Q9UJY6
Alternative splicing: 3 isoforms:  Q92496-1   Q92496-2   Q92496-3   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for CFHR4: NX_Q92496

Explore proteomics data for CFHR4 at MOPED

Post-translational modifications: 

  • Glycosylated1
  • Glycosylation2 at Asn127, Asn186, Asn206, Asn374, Asn433, Asn453, Asn557

  • See CFHR4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001188479.1  NP_001188480.1  NP_006675.2  

    ENSEMBL proteins: 
     ENSP00000477162   ENSP00000356386   ENSP00000251424   ENSP00000356388  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    complement: Complement system

    1 InterPro protein domain:
     IPR000436 Sushi_SCR_CCP

    Graphical View of Domain Structure for InterPro Entry Q92496

    ProtoNet protein and cluster: Q92496

    1 Blocks protein domain: IPB000436 Sushi domain/SCR domain/CCP module

    UniProtKB/Swiss-Prot: FHR4_HUMAN, Q92496
    Similarity: Contains 9 Sushi (CCP/SCR) domains


    CFHR4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: FHR4_HUMAN, Q92496
    Function: Involved in complement regulation. Can associate with lipoproteins and may play a role in lipid
    metabolism

         Gene Ontology (GO): 1 molecular function term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005319lipid transporter activity TAS9038172
         
    CFHR4 for ontologies           About GeneDecksing


    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CFHR4
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CFHR4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for CFHR4

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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    FHR4_HUMAN, Q92496: Secreted
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region IEA--

    CFHR4 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for CFHR4
    Interactions:

        Search GeneGlobe Interaction Network for CFHR4

    STRING Interaction Network Preview (showing 2 interactants - click image to see more details)

    3 Interacting proteins for CFHR4 (Q924963 ENSP000002514244) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    C3P010243, ENSP000002459074I2D: score=2 STRING: ENSP00000245907
    CDC42P609533, ENSP000003144584I2D: score=2 STRING: ENSP00000314458
    CRPP027413I2D: score=1 
    About this table

    Gene Ontology (GO): 1 biological process term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006869lipid transport TAS9038172

    CFHR4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for CFHR4 (FHR4)

    1 Novoseek inferred chemical compound relationship for CFHR4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    heparin 37.9 3 10622723 (2), 10408366 (1)



    CFHR4 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for CFHR4 gene (3 alternative transcripts): 
    NM_001201550.2  NM_001201551.1  NM_006684.4  

    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000608469 ENST00000367416(uc021pgt.1 uc009wyy.3 uc001gtp.3 uc001gto.3)
    ENST00000251424 ENST00000367418
    miRNA
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    Primer
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      QuantiFast Probe-based Assays in human, mouse, rat CFHR4

    4 AceView cDNA sequences:

    BC074957 NM_006684 X98337 AV682723 

    GeneLoc Exon Structure

    5 Alternative Splicing Database (ASD) splice patterns (SP) for CFHR4    About this scheme

    ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b · 11c
    SP1:                                                  -                                 
    SP2:                    -     -     -     -           -                                 
    SP3:                                                  -     -                           
    SP4:                                                                                    
    SP5:                                                        -                           


    ECgene alternative splicing isoforms for CFHR4

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CFHR4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    CFHR4 Expression
    About this image

    CFHR4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CFHR4 Protein Expression

    UniProtKB/Swiss-Prot: FHR4_HUMAN, Q92496
    Tissue specificity: Expressed by the liver and secreted in plasma

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    In Situ
    Assay Products:
     

     
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for CFHR4 gene from Selected species (see all 9)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    chicken
    (Gallus gallus)
    Aves --
    Uncharacterized protein
    13(a)
    1 → many
    8(2641142-2673492)
    lizard
    (Anolis carolinensis)
    Reptilia --
    Uncharacterized protein
    5(a)
    many ↔ many
    GL343440.1(798097-827033)
    zebrafish
    (Danio rerio)
    Actinopterygii cfhl16
    CU463157.16
    Uncharacterized protein
    15(a)
    11(a)
    many ↔ many
    many ↔ many
    22(24192537-24206113) ENSDARG00000056771
    22(23247895-23276748) ENSDARG00000056845
            Species with no ortholog for CFHR4

    ENSEMBL Gene Tree for CFHR4 (if available)
    TreeFam Gene Tree for CFHR4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CFHR4 gene
    F13B2  CFHR22  CFHR52  CFHR32  CFH2  CFHR12  
    5 SIMAP similar genes for CFHR4 using alignment to 3 protein entries:     FHR4_HUMAN (see all proteins):
    CFHR3    CFHR1    CFHR5    CFH    CFHR2

    CFHR4 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for CFHR4 (see all 848)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs2005046681,2
    C--168026907(-) TAAAGA/CANNNN 3 -- int10--------
    rs1495711151,2
    C--168041384(+) GACTT-/AAAAAA 3 -- int10--------
    rs24779981,2
    --168043839(-) TTTCAC/TTTTTG 3 -- int10--------
    rs24779971,2
    H--168043885(-) gccTAA/GTTCTT 3 -- int16Minor allele frequency- G:0.00NS EA NA 384
    rs1116278201,2
    C--196864019(+) CTAAAAACAA   
      CAAC
    /-
    AACAA
    3 -- cds11Minor allele frequency- -:0.50CSA 2
    rs568669211,2
    C--196864021(+) AACAACAACA   
      ACAA
    /-
    ATTAT
    3 -- cds11Minor allele frequency- -:0.00NA 2
    rs359668841,2
    C--196868282(+) CAATAG/-GGGTG 3 -- int11Minor allele frequency- -:0.50NA 2
    rs360515211,2
    C--196869447(+) TGGAA-/TTTTTT 3 -- int10--------
    rs785281451,2
    C--196877183(+) TATCAG/CAAGAA 3 -- int12Minor allele frequency- C:0.00NA CSA 3
    rs800587611,2
    C--196877202(-) TGTGGA/C/TGTTTG 3 -- int15NA CSA 8

    HapMap Linkage Disequilibrium report for CFHR4 (196819371 - 196888102 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for CFHR4 (see all 54):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2667193CNV Deletion23128226
    esv2672620CNV Deletion23128226
    esv2421550CNV Deletion20811451
    dgv88e199CNV Deletion23128226
    esv5113CNV Deletion18987735
    dgv55e201CNV Deletion23290073
    dgv54e201CNV Deletion23290073
    nsv471354CNV Duplication19718026
    dgv3n31CNV Duplication19718026
    dgv25n16CNV Insertion17901297

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 605337    OMIM disorders: --

    8 diseases for CFHR4:    
    About MalaCards
    kuhnt-junius degeneration    atypical hemolytic-uremic syndrome    hemolytic-uremic syndrome    age related macular degeneration
    systemic lupus erythematosus    lupus erythematosus    hepatitis b    hepatitis

    1 disease from the University of Copenhagen DISEASES database for CFHR4:
    Kuhnt-Junius degeneration

    CFHR4 for disorders           About GeneDecksing

    Genetic Association Database (GAD): CFHR4
    Human Genome Epidemiology (HuGE) Navigator: CFHR4 (5 documents)

    Export disorders for CFHR4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CFHR4 gene, integrated from 10 sources (see all 27):
    (articles sorted by number of sources associating them with CFHR4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The human factor H-related protein 4 (FHR-4). A novel short consensus repeat-containing protein is associated with human triglyceride-rich lipoproteins. (PubMed id 9038172)1, 2, 3, 9 Skerka C.... Zipfel P.F. (J. Biol. Chem. 1997)
    2. Biochemical and functional characterization of the factor-H-related protein 4 (FHR-4). (PubMed id 9476126)1, 2, 9 Hellwage J.... Zipfel P.F. (Immunopharmacology 1997)
    3. Epidemiological approach to identifying genetic predispositions for atypical hemolytic uremic syndrome. (PubMed id 20059470)1, 4 Sullivan M....Neumann H.P. (Ann. Hum. Genet. 2010)
    4. The NEI/NCBI dbGAP database: genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration. (PubMed id 18541031)1, 4 Zhang H....Deangelis M.M. (BMC Med. Genet. 2008)
    5. Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: characterization, ethnic distribution and evolutionary implications. (PubMed id 17438673)1, 4 Hageman G.S....Dean M. (Ann. Med. 2006)
    6. FHR-4A: a new factor H-related protein is encoded by the human FHR-4 gene. (PubMed id 15562282)1, 2 Jozsi M.... Zipfel P.F. (Eur. J. Hum. Genet. 2005)
    7. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    8. A radiation hybrid map of complement factor H and factor H-related genes. (PubMed id 10380701)1, 3 DA-az-GuillAcn M.A....Heine-SuA+er D. (Immunogenetics 1999)
    9. Human complement factor H-related protein 4 binds and recruits native pentameric C-reactive protein to necrotic cells. (PubMed id 19084272)1, 9 Mihlan M....JA^zsi M. (Mol. Immunol. 2009)
    10. Molecular basis of C-reactive protein binding and modulation of complement activation by factor H-related protein 4. (PubMed id 20042240)1, 9 Hebecker M....JA^zsi M. (Mol. Immunol. 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 10877 HGNC: 16979 AceView: CFHL4 Ensembl:ENSG00000134365 euGenes: HUgn10877
    ECgene: CFHR4 H-InvDB: CFHR4

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for CFHR4 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CFHR4 gene:
    Search GeneIP for patents involving CFHR4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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