CFH

Protein identityUniProt · HPA

UniProt accession

P08603

Gene

CFH

Ensembl

ENSG00000000971

Chromosome

1

Canonical length

1231 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Vesicles

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Oct 2011]

Canonical amino-acid sequenceUniProt

1231 residues, UniProt reviewed canonical sequence.

>P08603|CFH
     1  MRLLAKIICL MLWAICVAED CNELPPRRNT EILTGSWSDQ TYPEGTQAIY KCRPGYRSLG
    61  NVIMVCRKGE WVALNPLRKC QKRPCGHPGD TPFGTFTLTG GNVFEYGVKA VYTCNEGYQL
   121  LGEINYRECD TDGWTNDIPI CEVVKCLPVT APENGKIVSS AMEPDREYHF GQAVRFVCNS
   181  GYKIEGDEEM HCSDDGFWSK EKPKCVEISC KSPDVINGSP ISQKIIYKEN ERFQYKCNMG
   241  YEYSERGDAV CTESGWRPLP SCEEKSCDNP YIPNGDYSPL RIKHRTGDEI TYQCRNGFYP
   301  ATRGNTAKCT STGWIPAPRC TLKPCDYPDI KHGGLYHENM RRPYFPVAVG KYYSYYCDEH
   361  FETPSGSYWD HIHCTQDGWS PAVPCLRKCY FPYLENGYNQ NYGRKFVQGK SIDVACHPGY
   421  ALPKAQTTVT CMENGWSPTP RCIRVKTCSK SSIDIENGFI SESQYTYALK EKAKYQCKLG
   481  YVTADGETSG SITCGKDGWS AQPTCIKSCD IPVFMNARTK NDFTWFKLND TLDYECHDGY
   541  ESNTGSTTGS IVCGYNGWSD LPICYERECE LPKIDVHLVP DRKKDQYKVG EVLKFSCKPG
   601  FTIVGPNSVQ CYHFGLSPDL PICKEQVQSC GPPPELLNGN VKEKTKEEYG HSEVVEYYCN
   661  PRFLMKGPNK IQCVDGEWTT LPVCIVEEST CGDIPELEHG WAQLSSPPYY YGDSVEFNCS
   721  ESFTMIGHRS ITCIHGVWTQ LPQCVAIDKL KKCKSSNLII LEEHLKNKKE FDHNSNIRYR
   781  CRGKEGWIHT VCINGRWDPE VNCSMAQIQL CPPPPQIPNS HNMTTTLNYR DGEKVSVLCQ
   841  ENYLIQEGEE ITCKDGRWQS IPLCVEKIPC SQPPQIEHGT INSSRSSQES YAHGTKLSYT
   901  CEGGFRISEE NETTCYMGKW SSPPQCEGLP CKSPPEISHG VVAHMSDSYQ YGEEVTYKCF
   961  EGFGIDGPAI AKCLGEKWSH PPSCIKTDCL SLPSFENAIP MGEKKDVYKA GEQVTYTCAT
  1021  YYKMDGASNV TCINSRWTGR PTCRDTSCVN PPTVQNAYIV SRQMSKYPSG ERVRYQCRSP
  1081  YEMFGDEEVM CLNGNWTEPP QCKDSTGKCG PPPPIDNGDI TSFPLSVYAP ASSVEYQCQN
  1141  LYQLEGNKRI TCRNGQWSEP PKCLHPCVIS REIMENYNIA LRWTAKQKLY SRTGESVEFV
  1201  CKRGYRLSSR SHTLRTTCWD GKLEYPTCAK R

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CFH 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

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

1,586 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CFH.

Disease | AllUniProt

Conditions CFH is implicated in, by any mechanism.

• Basal laminar drusen (BLD) MIM:126700
• Complement factor H deficiency (CFHD) MIM:609814
• Hemolytic uremic syndrome, atypical, 1 (AHUS1) MIM:235400
• Macular degeneration, age-related, 4 (ARMD4) MIM:610698

Disease | GeneticClinVar

222 pathogenic / likely-pathogenic of 1,586 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Atypical hemolytic-uremic syndrome
• Age related macular degeneration 4
• Factor H deficiency
• Hemolytic uremic syndrome, atypical, susceptibility to, 1
• Basal laminar drusen

Disease | ImmuneIEDB

Conditions an epitope on CFH was assayed in.

• rheumatoid arthritis B cell
• lung non-small cell carcinoma B cell
• hemolytic-uremic syndrome B cell
• neuromyelitis optica B cell
• Sjogren's syndrome B cell

Disease | AutoantibodyPubMed

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

• Glomerulonephritis 13
• Kidney Failure, Chronic 9
• Kidney Diseases 8
• Purpura, Thrombotic Thrombocytopenic 8
• Lung Neoplasms 7
• Paraproteinemias 6
• Proteinuria 6
• Glomerulonephritis, Membranous 5
• Myositis 5
• Acute Kidney Injury 4
• Antiphospholipid Syndrome 4
• Lupus Nephritis 4
• COVID-19 3
• Lupus Erythematosus, Systemic 3

Showing 14 of 18 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for CFH 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)

0.32

gnomAD pLI

0.86

gnomAD missense Z

1

DepMap mean gene effect

-0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• central nervous system myelination
• complement activation
• complement activation, alternative pathway
• inflammatory response
• proteolysis
• regulation of complement activation
• regulation of complement-dependent cytotoxicity
• regulation of complement activation, alternative pathway

Molecular functions

• complement component C3b binding
• heparan sulfate proteoglycan binding
• heparin binding
• identical protein binding

Cellular components

• blood microparticle
• extracellular exosome
• extracellular region
• extracellular space
• serine-type endopeptidase complex
• symbiont cell surface

Protein domainsUniProt · Pfam · InterPro

• Sushi/SCR/CCP domain
• Sushi/SCR/CCP superfamily
• Complement System Regulators and Virion Entry Mediators
• Sushi repeat (SCR repeat)

KeywordsUniProt

• Age-related macular degeneration
• Complement alternate pathway
• Disulfide bond
• Glycoprotein
• Hemolytic uremic syndrome
• Host-virus interaction
• Immunity
• Innate immunity
• Repeat
• Secreted
• Signal
• Sulfation
• Sushi

InteractionsUniProt · HPA

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

• C3