Details for: CFHR1

Gene ID: 3078

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CFHR1

Ensembl ID: ENSG00000244414

Description: complement factor H related 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • midzonal region hepatocyte CL0019028
    CSI 5.32
    rCSI 12.48%
    PRS 99.24
  • periportal region hepatocyte CL0019026
    CSI 3.32
    rCSI 12.91%
    PRS 99.13
  • hepatocyte CL0000182
    CSI 3.31
    rCSI 5.93%
    PRS 99.14
  • centrilobular region hepatocyte CL0019029
    CSI 2.67
    rCSI 6.97%
    PRS 98.99
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.7
    rCSI 4.93%
    PRS 99.62

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CFHR1](/details-gene/3078) (Complement Factor H Related 1) is a protein-coding gene located on chromosome 1q31.3. It belongs to a family of plasma proteins structurally related to complement factor H ([Link](https://pubmed.ncbi.nlm.nih.gov/1826708/), [Link](https://doi.org/10.1016/0167-5699(94)90155-4)). As a secreted glycoprotein, [CFHR1](/details-gene/3078) is a key component of the innate immune system, primarily involved in the regulation of the [complement cascade](/details-pathway/R-HSA-166658). Expression data strongly indicates that [CFHR1](/details-gene/3078) is synthesized predominantly by [hepatocytes](/details-cell/CL0000182), the main parenchymal cells of the liver. Clinically, deletions involving the [CFHR1](/details-gene/3078) gene are strongly associated with atypical hemolytic uremic syndrome (aHUS) ([Link](https://omim.org/entry/134371)), highlighting its critical role in preventing excessive complement activation on host cell surfaces ([Link](https://doi.org/10.1371/journal.pgen.0030041)). ## Cellular Roles and Expression Landscape The expression profile of [CFHR1](/details-gene/3078) points to a highly specialized function originating from the liver. **Overall**, the gene shows its most significant expression in liver parenchymal cells, consistent with its role as a secreted serum protein. The top-ranked cell types are all subtypes of [hepatocytes](/details-cell/CL0000182), underscoring the liver as the primary site of synthesis: * **[midzonal region hepatocyte](/details-cell/CL0019028)** (CSI: 5.32) * **[periportal region hepatocyte](/details-cell/CL0019026)** (CSI: 3.32) * **[hepatocyte](/details-cell/CL0000182)** (CSI: 3.31) * **[centrilobular region hepatocyte](/details-cell/CL0019029)** (CSI: 2.67) This pattern suggests that [CFHR1](/details-gene/3078) production is a constitutive and fundamental function of [hepatocytes](/details-cell/CL0000182) across different metabolic zones of the liver lobule, ensuring stable levels of the protein in circulation. The slightly elevated significance in [midzonal region hepatocytes](/details-cell/CL0019028) may suggest a potential link to specific metabolic activities within this zone. Minor significance is also noted in [microcirculation associated smooth muscle cells](/details-cell/CL0008035) (CSI: 1.70), although its functional relevance in this cell type requires further investigation. The absence of other immune or structural cells in the top-ranked list emphasizes its specific hepatic origin. ## Pathways and Molecular Function [CFHR1](/details-gene/3078) is an integral part of the [Innate Immune System](/details-pathway/R-HSA-168249), with its functions centered on modulating the complement system. Functional annotations reveal its direct participation in the [Regulation of complement cascade](/details-pathway/R-HSA-977606). **Biological Processes:** * As a regulator, it is involved in [complement activation](/details-ontology/GO:0006956). Its ability to compete with Factor H for binding to C3b suggests it modulates the alternative pathway of complement. It can also form dimers, which appears to be important for its function in vivo ([Link](https://doi.org/10.1073/pnas.1219260110)). **Molecular Functions:** * Its primary molecular role is through [protein binding](/details-ontology/GO:0005515), particularly [complement component C3b binding](/details-ontology/GO:0001851). This interaction is central to its regulatory capacity within the complement cascade. It also engages in [identical protein binding](/details-ontology/GO:0042802), forming homodimers and heterodimers with other CFHR proteins. **Cellular Components:** * Consistent with its function as a plasma protein synthesized in the liver, [CFHR1](/details-gene/3078) is localized to the [extracellular region](/details-ontology/GO:0005576) and [extracellular space](/details-ontology/GO:0005615). It is also found as a component of [blood microparticles](/details-ontology/GO:0072562), suggesting it may associate with cell-derived vesicles in circulation. ## Research Directions The established link between [CFHR1](/details-gene/3078) deficiency and atypical hemolytic uremic syndrome (aHUS) provides a strong foundation for further investigation into its protective mechanisms. Understanding its precise regulatory role is critical for developing targeted therapies. **Proposed Hypotheses:** 1. **Hepatocyte-specific loss of [CFHR1](/details-gene/3078) is a primary driver of endothelial susceptibility to complement-mediated damage in aHUS.** Given that [hepatocytes](/details-cell/CL0000182) are the main source of circulating [CFHR1](/details-gene/3078), a reduction in its synthesis, whether due to genetic deletion or liver pathology, may systemically lower the threshold for complement activation on endothelial surfaces, predisposing individuals to thrombotic microangiopathies. 2. **[CFHR1](/details-gene/3078) acts as a competitive antagonist of CFH at specific tissue sites.** While related to the complement inhibitor Factor H (CFH), [CFHR1](/details-gene/3078) lacks a key regulatory domain. It may therefore function to locally *promote* complement activation by displacing the inhibitor CFH from surfaces, a role that could be beneficial for clearing pathogens but detrimental when dysregulated. **Key Experimental Approach:** * To test the first hypothesis, a liver-specific knockout mouse model could be generated using Cre-Lox technology (e.g., Albumin-Cre crossed with a floxed *Cfhr1* mouse). These mice, lacking hepatocyte-derived [CFHR1](/details-gene/3078), would be challenged with an aHUS trigger, such as Shiga toxin or nephrotoxic serum. The primary endpoints would be the assessment of kidney function (serum creatinine, proteinuria), platelet counts, and histological evidence of thrombotic microangiopathy in the glomeruli. Comparing these outcomes to wild-type littermates would directly test the role of hepatic [CFHR1](/details-gene/3078) in protecting the microvasculature. **Therapeutic Potential:** * Given that deficiency of [CFHR1](/details-gene/3078) is associated with pathology, the primary therapeutic strategy would be **activation or protein replacement**, not inhibition. For patients with aHUS linked to *CFHR1* deletions and subsequent development of anti-Factor H autoantibodies ([Link](https://doi.org/10.1182/blood-2007-09-109876)), a recombinant [CFHR1](/details-gene/3078) protein could be a potential therapeutic. Such a therapy could restore normal complement regulation on endothelial cells, representing a targeted approach to treating this specific subset of aHUS patients.

Genular Protein ID: 4019353817

Symbol: FHR1_HUMAN

Name: Complement factor H-related protein 1

UniProtKB Accession Codes:

Q03591 A8K465 Q3B774 Q9UJ17

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniProtKB 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1826708

Title: Cloning of the 1.4-kb mRNA species of human complement factor H reveals a novel member of the short consensus repeat family related to the carboxy terminal of the classical 150-kDa molecule.

PubMed ID: 1826708

PubMed ID: 10781834

Title: Complement factor H: sequence analysis of 221 kb of human genomic DNA containing the entire fH, fHR-1 and fHR-3 genes.

PubMed ID: 10781834

DOI: 10.1016/s0161-5890(00)00024-9

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 1711047

Title: Molecular cloning of a human serum protein structurally related to complement factor H.

PubMed ID: 1711047

DOI: 10.1016/s0021-9258(18)99058-7

PubMed ID: 1825108

Title: Two major serum components antigenically related to complement factor H are different glycosylation forms of a single protein with no factor H-like complement regulatory functions.

PubMed ID: 1825108

PubMed ID: 8172644

Title: Complement factor H and related proteins: an expanding family of complement-regulatory proteins?

PubMed ID: 8172644

DOI: 10.1016/0167-5699(94)90155-4

PubMed ID: 16335952

Title: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.

PubMed ID: 16335952

DOI: 10.1021/pr0502065

PubMed ID: 17367211

Title: Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome.

PubMed ID: 17367211

DOI: 10.1371/journal.pgen.0030041

PubMed ID: 18006700

Title: Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency.

PubMed ID: 18006700

DOI: 10.1182/blood-2007-09-109876

PubMed ID: 23204165

Title: Glycerol-3-phosphate dehydrogenase 2 is a novel factor H-, factor H-like protein 1-, and plasminogen-binding surface protein of Candida albicans.

PubMed ID: 23204165

DOI: 10.1093/infdis/jis718

PubMed ID: 23487775

Title: Dimerization of complement factor H-related proteins modulates complement activation in vivo.

PubMed ID: 23487775

DOI: 10.1073/pnas.1219260110

Sequence Information:

  • Length: 330
  • Mass: 37651
  • Checksum: C0A1B38B8B34B6EF
  • Sequence:
    • MWLLVSVILI SRISSVGGEA TFCDFPKINH GILYDEEKYK PFSQVPTGEV FYYSCEYNFV 
SPSKSFWTRI TCTEEGWSPT PKCLRLCFFP FVENGHSESS GQTHLEGDTV QIICNTGYRL 
QNNENNISCV ERGWSTPPKC RSTDTSCVNP PTVQNAHILS RQMSKYPSGE RVRYECRSPY 
EMFGDEEVMC LNGNWTEPPQ CKDSTGKCGP PPPIDNGDIT SFPLSVYAPA SSVEYQCQNL 
YQLEGNKRIT CRNGQWSEPP KCLHPCVISR EIMENYNIAL RWTAKQKLYL RTGESAEFVC 
KRGYRLSSRS HTLRTTCWDG KLEYPTCAKR