CFHR5

Last update 08 May 2025

Basic Info

Synonyms

CFHL5, CFHR5, complement factor H related 5

+ [3]

Introduction

Involved in complement regulation. The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological complement inhibitor CFH.

100 Clinical Results associated with CFHR5

100 Translational Medicine associated with CFHR5

0 Patents (Medical) associated with CFHR5

160

Literatures (Medical) associated with CFHR5

01 Apr 2025·The American Journal of Human Genetics

Rare predicted loss-of-function and damaging missense variants in CFHR5 associate with protection from age-related macular degeneration

Article

Author: Akle Serrano, Sebastian ; Ward, Lucas D ; Deaton, Aimee M ; Walshe, Tony E ; Ticau, Simina ; Nioi, Paul ; Holleman, Aaron M ; Krohn, Lynne ; Hoffing, Rachel A ; LoGerfo, Philip ; Plekan, Mollie E ; Borodovsky, Anna

Age-related macular degeneration (AMD) is a leading cause of blindness among older adults worldwide, but treatment options are limited. Genetics studies have implicated the CFH locus, containing CFH and five CFHR genes, CFHR1-5, in AMD. While CFH has been robustly linked with AMD risk, potential additional roles for the CFHR genes remain unclear, obscured by strong linkage disequilibrium across the locus. Investigating rare coding variants can help to identify causal genes in such regions. We used whole-exome sequencing data from 406,952 UK Biobank participants to examine AMD associations with genes at the CFH locus. For each gene, we used burden testing to examine associations of rare (minor-allele frequency [MAF] < 1%) predicted loss-of-function (pLoF) and predicted damaging missense variants with AMD. We considered "broadly defined AMD" (ICD-10 35.3; n_cases = 10,700) and "strictly defined AMD" (dry or wet AMD; n_cases = 346). Adjusting for CFH-region variants known to independently associate with AMD, we find that CFHR5 rare variant burden significantly associates with a decreased risk of broadly defined AMD (odds ratio [OR] = 0.75, p = 7 × 10^-4), with this association primarily driven by pLoF variants. Furthermore, the association of CFHR5 rare variants with AMD protection is estimated to be stronger for individuals with the CFH rs1061170 AMD risk allele (p.Tyr402His [p.Y402H]; interaction p = 0.04). Corresponding analyses of strict AMD were underpowered. However, we observe that thinning of the photoreceptor layer outer segment strongly predicts strict AMD and find that CFHR5 rare variant burden is significantly associated with increased thickness of this retinal layer (+0.34 SD, p = 4 × 10^-4, n = 45,365). These findings suggest CFHR5 inhibition as a potential therapeutic approach for AMD.

01 Dec 2024·Cytokine

Complement factor H-related protein 5 alleviates joint inflammation and osteoclast differentiation by disrupting RANK-JNK signaling in collagen antibody-induced arthritis mouse model

Article

Author: Kim, Tae-Hwan ; Kim, Sang-Hyon ; Kim, Dongju ; Jeon, Chanhyeok ; Lee, Seung Hoon ; Son, Chang-Nam ; Jo, Sungsin ; Kim, Jong-Seo ; Kim, Kyung-Me ; Kang, Young Mo ; Lee, Ji-Hyun

BACKGROUNDComplement Factor H-Related protein 5 (CFHR5) belongs to the factor H/CFHR family and regulates the complement system by modulating factor H's inhibitory activity against C3b. Despite its known role, the impact of CFHR5 on autoimmune arthritis and its relationship to pathophysiological changes in arthritis and bone loss remain unclear. This study aimed to assess the effect of CFHR5 on aggressive osteoclast activity and arthritis using a murine model of collagen antibody-induced arthritis (CAIA).METHODSThe effect of recombinant CFHR5 protein (rCFHR5) on arthritis were evaluated in CAIA. The mice were divided into three group and intraperitoneally treated with rCFHR5, methotrexate (MTX) as positive control or PBS as negative control. In the CAIA mouse model, the rCFHR5-treated group significantly reduced the incidence and clinical arthritis equivalent to the MTX group. Clinical arthritis scores, incidence and body weight were measured, and histological analysis of ankle joints was performed by Hematoxylin and Eosin (H&E) and Safranin O - Fast green (SOFG), Tartrate-resistant acid phosphatase (TRAP) staining and Immunohistochemistry. Moreover, to investigate the rCFHR5 role, we isolated murine osteoclast precursor cells (OCPs) from each group, induced osteoclasts with M-CSF and RANKL, and performed TRAP and F-actin staining. To verify the mechanism, mRNA and protein analyses were performed in OCPs.RESULTSHistological examination of ankle joints revealed substantial reductions in synovial hyperplasia, bone marrow inflammation, bone erosion, cartilage destruction and TRAP-positive cells in the rCFHR5 group compared to the vehicle group. The ankle joints of the rCFHR5 group showed markedly decreased expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6). Mechanically, treatment with rCFHR5 inhibited RANKL-mediated osteoclast differentiation from OCPs and disrupted the RANK-JNK signaling. These findings demonstrate that treatment with rCFHR5 attenuates joint inflammation and reduces osteoclast differentiation, indicating its potential anti-inflammatory effect in autoimmune arthritis models.

04 Oct 2024·Journal of Proteome Research

Proteome and Metabolome Profiling of Anticoagulant Disorders Induced by Familial Protein S Deficiency

Article

Author: Liu, Binjie ; Chen, Yongxv ; He, Zhuoru ; Zhang, Caiping ; Huang, Huiting ; Zhang, Yimin ; Liu, Zhongqiu ; Xie, Yue

Protein S deficiency (PSD) is an autosomal dominant disorder characterized by congenital thrombophilia. Studies on PSD are limited yet, resulting in a lack of clarity about molecular changes during abnormal coagulation. Proteomics and metabolomics analyses were conducted on the plasma of PSD patients based on liquid and gas chromatography-mass spectrometry (LC- and GC-MS). Differential proteins and metabolites of PSD were then filtered by univariate statistical analysis and subjected to network analysis using the ingenuity pathway analysis (IPA) platform. The proteome and metabolome of PSD were obviously disturbed, and the biological pathway of coagulation and complement cascades was the most affected. During PSD, overall levels of anticoagulant protein decreased and negative regulation of thrombin production was reduced, causing the formation of fibrin clots and platelet aggregation. Furthermore, 9 differential proteins correlated significantly with protein S, comprising A2M, AGT, APOE, FGG, GPLD1, IGHV1-69, CFHR5, CPN2, and CA1. The biological networks suggested that the pathways of acute phase response, FXR/RXR activation, serotonin receptor signaling, and p70S6K signaling were associated with PSD, indicating an interaction disorder of inflammatory immune and lipid metabolism. The findings may contribute to knowledge of available functional molecules and biological pathways of familial PSD and help with treatment improvement. Data are available via ProteomeXchange with identifier PXD055111 and MetaboLights with reference number MTBLS2653.

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