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    CFHR4 complement factor H related 4 [ Homo sapiens (human) ]

    Gene ID: 10877, updated on 5-Mar-2024

    Summary

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    Official Symbol
    CFHR4provided by HGNC
    Official Full Name
    complement factor H related 4provided by HGNC
    Primary source
    HGNC:HGNC:16979
    See related
    Ensembl:ENSG00000134365 MIM:605337; AllianceGenome:HGNC:16979
    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
    FHR4; CFHL4; FHR-4
    Summary
    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]
    Expression
    Restricted expression toward liver (RPKM 22.1) See more
    Orthologs
    all
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    Genomic context

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    See CFHR4 in Genome Data Viewer
    Location:
    1q31.3
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (196888052..196918633)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (196149839..196180430)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (196857182..196887763)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene complement factor H related 1 Neighboring gene complement factor H-related protein 3-like Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:196827453-196828652 Neighboring gene Sharpr-MPRA regulatory region 8052 Neighboring gene uncharacterized LOC105371675 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:196902813-196903312 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:196910913-196911413 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2275 Neighboring gene complement factor H related 2 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:196960781-196961380 Neighboring gene complement factor H related 5

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Identification of CFHR4 as a Potential Prognosis Biomarker Associated With lmmune Infiltrates in Hepatocellular Carcinoma. Yu H, et al. Front Immunol, 2022. PMID 35812416, Free PMC Article
    2. Increased circulating levels of Factor H-Related Protein 4 are strongly associated with age-related macular degeneration. Cipriani V, et al. Nat Commun, 2020 Feb 7. PMID 32034129, Free PMC Article
    3. FHR-4A: a new factor H-related protein is encoded by the human FHR-4 gene. Józsi M, et al. Eur J Hum Genet, 2005 Mar. PMID 15562282
    4. Biochemical and functional characterization of the factor-H-related protein 4 (FHR-4). Hellwage J, et al. Immunopharmacology, 1997 Dec. PMID 9476126
    5. The human factor H-related protein 4 (FHR-4). A novel short consensus repeat-containing protein is associated with human triglyceride-rich lipoproteins. Skerka C, et al. J Biol Chem, 1997 Feb 28. PMID 9038172

    See all (31) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.
      Title: Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.
    2. CFH and CFHR structural variants in atypical Hemolytic Uremic Syndrome: Prevalence, genomic characterization and impact on outcome.
      Title: CFH and CFHR structural variants in atypical Hemolytic Uremic Syndrome: Prevalence, genomic characterization and impact on outcome.
    3. Identification of CFHR4 as a Potential Prognosis Biomarker Associated With lmmune Infiltrates in Hepatocellular Carcinoma.
      Title: Identification of CFHR4 as a Potential Prognosis Biomarker Associated With lmmune Infiltrates in Hepatocellular Carcinoma.
    4. FHR-4 as a key molecular player contributing to complement dysregulation in the age-related macular degeneration.FHR-4 is expressed in the liver but not in the eye.
      Title: Increased circulating levels of Factor H-Related Protein 4 are strongly associated with age-related macular degeneration.
    5. The SNP rs3753396 in CFH and SNP rs6685931 in CFHR4 are associated with systemic complement activation levels. The SNP rs6685931 in CFHR4 and its linked haplotype H1-2 also conferred a risk for age-related macular degeneration (AMD) development, and therefore could be used to identify AMD patients who would benefit most from complement-inhibiting therapies.
      Title: Genome-Wide Association Study Reveals Variants in CFH and CFHR4 Associated with Systemic Complement Activation: Implications in Age-Related Macular Degeneration.
    6. Reports an association between a rare variant in the complement factor H-related 4 (CFHR4) gene and phenytoin-induced maculopapular exanthema in Europeans. This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity.
      Title: Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients.
    7. The combination of three proteins - apolipoprotein A-IV, complement factor H-related protein 4 and platelet basic protein - demonstrated the best classification performance for our data for diagnosis of growth hormone defic.
      Title: Identification of candidate serum biomarkers of childhood-onset growth hormone deficiency using SWATH-MS and feature selection.
    8. Next-generation sequencing of the CFH region identified putatively functional variants (missense, splice site and indel) on the four common haplotypes. We found no expression of any of the five CFH-related genes in the retina or RPE/Choroid/Sclera, in contrast to the liver, which is the main source of the circulating proteins. [CFHR4]
      Title: Sequence and Expression of Complement Factor H Gene Cluster Variants and Their Roles in Age-Related Macular Degeneration Risk.
    9. Studies indicate that complement factor H-related proteins (FHR1-5) may enhance complement activation, with important implications for the role of these proteins in disease.
      Title: Factor H-related proteins determine complement-activating surfaces.
    10. Factor H-related protein 4 activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with C3b protein
      Title: Factor H-related protein 4 activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with C3b protein.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    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

    Associated conditions

    Description Tests
    Atypical hemolytic-uremic syndrome
    MedGen: C2931788 GeneReviews: Genetic Atypical Hemolytic-Uremic Syndrome
    		Compare labs

    EBI GWAS Catalog

    Description
    Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis.
    EBI GWAS Catalog
    Genome-wide association study identifies susceptibility loci for IgA nephropathy.
    EBI GWAS Catalog
    Ischemic stroke is associated with the ABO locus: the EuroCLOT study.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables complement component C3b binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables lipid transporter activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in complement activation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in lipid transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    complement factor H-related protein 4

    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

    1. NG_028159.1 RefSeqGene

      Range
      5039..35620
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1224

    mRNA and Protein(s)

    1. NM_001201550.3 → NP_001188479.1  complement factor H-related protein 4 isoform 1 precursor

      See identical proteins and their annotated locations for NP_001188479.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1, also known as FHR-4A).
      Source sequence(s)
      AJ640130, AK292752, BX248415, X98337
      Consensus CDS
      CCDS91133.1
      UniProtKB/Swiss-Prot
      A8K9N7, B1ALQ9, C9J7J7, Q5DVJ7, Q92496, Q9UJY6
      Related
      ENSP00000477162.2, ENST00000608469.6
      Conserved Domains (3) summary
      cd00033
      Location:458 → 513
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      PHA02927
      Location:339 → 577
      PHA02927; secreted complement-binding protein; Provisional
      pfam00084
      Location:27 → 83
      Sushi; Sushi repeat (SCR repeat)

    2. NM_001201551.2 → NP_001188480.1  complement factor H-related protein 4 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate acceptor splice site in the 5' coding region compared to variant 1, resulting in an isoform (2) shorter by 1 aa compared to isoform 1.
      Source sequence(s)
      AJ640130, AK292752, BX248415
      Consensus CDS
      CCDS55671.1
      UniProtKB/Swiss-Prot
      Q92496
      Related
      ENSP00000356386.2, ENST00000367416.6
      Conserved Domains (3) summary
      cd00033
      Location:457 → 512
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      PHA02927
      Location:338 → 576
      PHA02927; secreted complement-binding protein; Provisional
      pfam00084
      Location:26 → 82
      Sushi; Sushi repeat (SCR repeat)

    3. NM_006684.5 → NP_006675.2  complement factor H-related protein 4 isoform 3 precursor

      See identical proteins and their annotated locations for NP_006675.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is missing four consecutive coding exons compared to variant 1. However, it maintains the reading frame and encodes isoform 3 (also known as FHR-4B), which is shorter but has the same N- and C-termini compared to isoform 1.
      Source sequence(s)
      AJ640130, AK292752, X98337
      Consensus CDS
      CCDS41451.1
      UniProtKB/Swiss-Prot
      Q92496
      Related
      ENSP00000251424.4, ENST00000251424.8
      Conserved Domains (3) summary
      cd00033
      Location:211 → 266
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      PHA02927
      Location:92 → 330
      PHA02927; secreted complement-binding protein; Provisional
      pfam00084
      Location:27 → 83
      Sushi; Sushi repeat (SCR repeat)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      196888052..196918633
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047440640.1 → XP_047296596.1  complement factor H-related protein 4 isoform X2

    2. XM_047440639.1 → XP_047296595.1  complement factor H-related protein 4 isoform X1

      Related
      ENST00000699463.1

    3. XM_017000111.2 → XP_016855600.1  complement factor H-related protein 4 isoform X3

    4. XM_017000113.2 → XP_016855602.1  complement factor H-related protein 4 isoform X5

    5. XM_047440659.1 → XP_047296615.1  complement factor H-related protein 4 isoform X4

    6. XM_047440683.1 → XP_047296639.1  complement factor H-related protein 4 isoform X6

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_025791754.1 Reference GRCh38.p14 PATCHES

      Range
      653141..683733
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054332739.1 → XP_054188714.1  complement factor H-related protein 4 isoform X7

    2. XM_054332735.1 → XP_054188710.1  complement factor H-related protein 4 isoform X2

    3. XM_054332734.1 → XP_054188709.1  complement factor H-related protein 4 isoform X1

    4. XM_054332736.1 → XP_054188711.1  complement factor H-related protein 4 isoform X3

    5. XM_054332738.1 → XP_054188713.1  complement factor H-related protein 4 isoform X5

    6. XM_054332737.1 → XP_054188712.1  complement factor H-related protein 4 isoform X4

    7. XM_054332740.1 → XP_054188715.1  complement factor H-related protein 4 isoform X6

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      196149839..196180430
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054333945.1 → XP_054189920.1  complement factor H-related protein 4 isoform X8

    2. XM_054333942.1 → XP_054189917.1  complement factor H-related protein 4 isoform X2

    3. XM_054333941.1 → XP_054189916.1  complement factor H-related protein 4 isoform X1

    4. XM_054333943.1 → XP_054189918.1  complement factor H-related protein 4 isoform X3

    5. XM_054333944.1 → XP_054189919.1  complement factor H-related protein 4 isoform X4

    6. XM_054333946.1 → XP_054189921.1  complement factor H-related protein 4 isoform X6

    RNA

    1. XR_008485879.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q92496.3 GenPept UniProtKB/Swiss-Prot:Q92496

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