Seroatlas · Human Serome Atlas

CFHR4

Complement factor H-related protein 4

Also known as: CFHL4, FHR-4, FHR4, FHR4_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q92496
Gene: CFHR4
Ensembl: ENSG00000134365
Chromosome: 1
Canonical length: 578 aa
Protein class: Plasma proteins, Predicted secreted proteins
Secretome location: Secreted to blood
Quaternary structure: Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

578 residues, UniProt reviewed canonical sequence.

>Q92496|CFHR4
     1  MLLLINVILT LWVSCANGQE VKPCDFPEIQ HGGLYYKSLR RLYFPAAAGQ SYSYYCDQNF
    61  VTPSGSYWDY IHCTQDGWSP TVPCLRTCSK SDVEIENGFI SESSSIYILN EETQYNCKPG
   121  YATAEGNSSG SITCLQNGWS TQPICIKFCD MPVFENSRAK SNGMWFKLHD TLDYECYDGY
   181  ESSYGNTTDS IVCGEDGWSH LPTCYNSSEN CGPPPPISNG DTTSFPQKVY LPWSRVEYQC
   241  QSYYELQGSK YVTCSNGDWS EPPRCISMKP CEFPEIQHGH LYYENTRRPY FPVATGQSYS
   301  YYCDQNFVTP SGSYWDYIHC TQDGWLPTVP CLRTCSKSDI EIENGFISES SSIYILNKEI
   361  QYKCKPGYAT ADGNSSGSIT CLQNGWSAQP ICIKFCDMPV FENSRAKSNG MRFKLHDTLD
   421  YECYDGYEIS YGNTTGSIVC GEDGWSHFPT CYNSSEKCGP PPPISNGDTT SFLLKVYVPQ
   481  SRVEYQCQSY YELQGSNYVT CSNGEWSEPP RCIHPCIITE ENMNKNNIQL KGKSDIKYYA
   541  KTGDTIEFMC KLGYNANTSV LSFQAVCREG IVEYPRCE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CFHR4 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: Secreted
Secreted: Yes
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.34
Highest tissue expression: 95 nTPM

Expression across tissuesHPA

Tissue

liver: 95 nTPM
kidney: 0.1 nTPM
adipose tissue: 0 nTPM
adrenal gland: 0 nTPM
amygdala: 0 nTPM
appendix: 0 nTPM

Single-cell type

hepatocytes: 63 nCPM
granulosa cells: 2.4 nCPM
foveolar cells: 1.2 nCPM
kupffer cells: 1 nCPM
other brain neurons: 0.5 nCPM
brain inhibitory neurons: 0.4 nCPM

Immune cell

basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM
MAIT T-cell: 0 nTPM

Brain region

amygdala: 0 nTPM
basal ganglia: 0 nTPM
cerebellum: 0 nTPM
cerebral cortex: 0 nTPM
choroid plexus: 0 nTPM
hippocampal formation: 0 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CFHR4.

Disease | ImmuneIEDB

Conditions an epitope on CFHR4 was assayed in.

rheumatoid arthritis B cell

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): 1.3
gnomAD pLI: 0
gnomAD missense Z: -1.17
DepMap mean gene effect: 0.17
DepMap dependency class: none

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

complement activation

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CFHR4 as an antibody target. Whether an autoantibody or antibody against CFHR4 could matter depends on whether native CFHR4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CFHR4 is annotated as secreted, so native CFHR4 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label CFHR4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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