Homo sapiens complex locus CFH, encoding complement factor H.
SUMMARY back to top
RefSeq summary
[CFH] This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short concensus 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].

RefSeq annotates 2 representative transcripts (NM included in AceView variants .a and .c), but Homo sapiens cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 15 spliced variants.

AceView synopsis, each blue text links to tables and details
Note that this locus is complex: it appears to produce several proteins with no sequence overlap.
Expression: According to AceView, this gene is expressed at very high level, 5.1 times the average gene in this release. The sequence of this gene is defined by 598 GenBank accessions from 538 cDNA clones, some from trachea (seen 83 times), corresponding non cancerous liver tissue (25), hepatocellular carcinoma (24), liver (24), cartilage (20), lung (20), uterus (19) and 110 other tissues. We annotate structural defects or features in 91 cDNA clones.
Alternative mRNA variants and regulation: The gene contains 29 distinct gt-ag introns. Transcription produces 21 different mRNAs, 15 alternatively spliced variants and 6 unspliced forms. There are 4 probable alternative promotors, 8 non overlapping alternative last exons and 7 validated alternative polyadenylation sites (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of a cassette exon, overlapping exons with different boundaries, splicing versus retention of 2 introns.
2 variants were isolated in vivo, despite the fact that they are predicted targets of nonsense mediated mRNA decay (NMD).
Efficacy of translation may be reduced by the presence of a shorter translated product (uORF) initiating at an AUG upstream of the main open reading frame (in variant fAug10, gAug10, iAug10, jAug10).
Function: There are 343 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (OMIM: Basal laminar drusen; Complement factor H deficiency; Hemolytic uremic syndrome, atypical, susceptibility to, 1; Macular degeneration, age-related, 4; Other sources: Arthritis, Rheumatoid; Atherosclerosis; Coronary Artery Disease; Ductus Arteriosus, Patent; Factor H and factor H-like 1 and 10 others), proposed to participate in pathway (Complement and coagulation cascades) and a process (complement activation, alternative pathway). Proteins are expected to localize in various compartments (membrane, nucleus, extracellular region). Putative protein interactors have been described (ADM, C3, CFHR3ANDCFHR1, CFI, CRP, DMP1, ITGAM, PTX3, SELEANDSELL, THBS1).
Protein coding potential: 15 spliced mRNAs putatively encode good proteins, altogether 15 different isoforms (9 complete, 4 COOH complete, 2 partial), some containing sushi domain (SCR repeat) [Pfam], some transmembrane domains [Psort2]. The remaining 6 mRNA variants (6 unspliced; 3 partial) appear not to encode good proteins. Finally proteins from this gene may be modulated by acetylation; phosphorylation, as detailed at PhosphoSite.

Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12.
Map on chromosome 1, links to other databases and other names
Map: This gene CFH maps on chromosome 1, at 1q32 according to Entrez Gene. In AceView, it covers 100.69 kb, from 196620883 to 196721568 (NCBI 37, August 2010), on the direct strand.
Links to: manual annotations from OMIM_235400, OMIM_126700, OMIM_609814, OMIM_610698, GAD, KEGG_04610, PhosphoSite, the SNP view, gene overviews from Entrez Gene 3075, GeneCards, expression data from ECgene, UniGene, molecular and other annotations from UCSC, or our GOLD analysis.
The previous AceView annotation is here.
Other names: The gene is also known as CFH, RP1-177P10.1, FH, HF, HF1, HF2, HUS, FHL1, AHUS1, ARMD4, ARMS1, CFHL3 or MGC88246, LOC3075. It has been described as complement factor H, beta-1H, factor H, factor H-like 1, beta-1-H-globulin, OTTHUMP00000034106, H factor 1 (complement), H factor 2 (complement), complement factor H, isoform b, age-related maculopathy susceptibility 1.
Closest AceView homologs in other species ?
The closest mouse genes, according to BlastP, are the AceView genes EG214403 (e=9 10-26), CfhandBC026782 (e=4 10-25), Cfhr1 (e=3 10-22).
The closest C.elegans genes, according to BlastP, are the AceView/WormGenes 1J826 (e=0.22), 1J467 (e=0.24), which may contain interesting functional annotation.
The closest A.thaliana gene, according to BlastP, is the AceView gene ATGLR2.4 (e=0.18), which may contain interesting functional annotation
RNA_seq discoveries back to top
Expression/conservation in primates tissues evaluated by cross-mapping to human. back to top
RNA-seq gene expression profile across 16 selected tissues from the Non-Human Primates Reference Transcriptome Resource (link to NHPRTR project).
- Primates: Apes (HUM: Human (Illumina BodyMap 2), CHP: Chimpanzee), Old World monkeys (PTM: Pig-Tailed Macaque, JMI Japanese Macaque, RMI Rhesus Macaque Indian, RMC Rhesus Macaque Chinese, CMM Cynomolgus Macaque Mauritian, CMC Cynomolgus Macaque Chinese, BAB Olive Baboon, SMY Sooty Mangabey); New World monkeys (MST common Marmoset, SQM Squirrel Monkey, OWL Owl Monkey); and Lemurs (MLM Mouse Lemur, RTL Ring-Tailed Lemur).
- The level for significantly expressed genes is color coded in 8 equal sized bins (light to dark green). Light gray is for weak not-accurately measured expression (2 to 8 reads above intergenic background); dark gray for no expression or no sequence conservation (0 read in gene). The plot to the right shows the distribution of measured expression values in all tissues for all genes (blue) and for this gene (green), in Magic index = log2(1000 sFPKM).
You may also examine the strand-specific genome coverage plots on the experimental AceView/Magic hub at UCSC, by tissue or by species. Tracks may be slow to load; please reload if some tracks come up yellow-greenish, and thanks to UCSC for the great work!.
          Complete gene on genome diagram: back to top
Please choose between the zoomable GIF version., and the Flash version.
This diagram shows in true scale the gene on the genome, the mRNAs and the cDNA clones.
Compact gene diagram back to top
Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron, the small numbers show the support of the introns in deep sequencing (with details in mouse-over) . Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript.
Sequences: click on the numbers to get the DNA back to top
mRNA variant mRNA matching the genome Best predicted protein 5' UTR 3' UTR uORF Upstream sequence Transcription
Downstream sequence
aAug10 4287 bp 1231 aa 365 bp 226 bp 2kb possibly including promoter 95787 bp 1kb
bAug10 6983 bp 751 aa 2730 bp 1997 bp 2kb possibly including promoter 70515 bp 1kb
cAug10 2124 bp 449 aa 240 bp 534 bp 2kb possibly including promoter 49988 bp 1kb
dAug10 1594 bp 424 aa 80 bp 239 bp 2kb probably including promoter 49533 bp 1kb
eAug10 1456 bp 385 aa 66 bp 232 bp 2kb probably including promoter 49512 bp 1kb
fAug10 1994 bp 364 aa 710 bp 189 bp 141 bp 2kb possibly including promoter 4003 bp 1kb
gAug10 1138 bp 292 aa 62 bp 197 bp 186 bp 2kb including Promoter 22777 bp 1kb
hAug10 938 bp 244 aa 201 bp 2kb 23892 bp 1kb
iAug10 862 bp 228 aa 177 bp 33 bp 2kb including Promoter 27834 bp 1kb
jAug10 604 bp 192 aa 26 bp 21 bp 2kb including Promoter 3289 bp 1kb
kAug10 505 bp 119 aa 144 bp 2kb 973 bp 1kb
lAug10 674 bp 101 aa 366 bp 2kb 1122 bp 1kb
mAug10 550 bp 88 aa 62 bp 221 bp 2kb probably including promoter 21352 bp 1kb
nAug10 552 bp 106 aa 74 bp 157 bp 2kb including Promoter 25487 bp 1kb
oAug10 537 bp 59 aa 356 bp 2kb 6522 bp 1kb
pAug10-unspliced 2462 bp 63 aa 2052 bp 218 bp 2kb including Promoter 2462 bp 1kb
qAug10-unspliced 829 bp 61 aa 276 bp 367 bp 2kb 829 bp 1kb
rAug10-unspliced 609 bp 48 aa 462 bp 2kb 609 bp 1kb
sAug10-unspliced 533 bp 69 aa 323 bp 2kb 533 bp 1kb
tAug10-unspliced 498 bp 32 aa 64 bp 335 bp 2kb probably including promoter 498 bp 1kb
uAug10-unspliced 363 bp 55 aa 193 bp 2kb 363 bp 1kb

Gene neighbors and Navigator on chromosome 1q32 back to top
ZOOM IN                D:disease,C:conserved,I:interactions,R:regulation,P:publications        
Annotated mRNA diagrams back to top
Bibliography:               343 articles in PubMed back to top
? Gene Summary Gene on genome mRNA:.a, .b, .c, .d, .e, .f, .g, .h, .i, .j, .k, .l, .m, .n, .o, .p-u, .q-u, .r-u, .s-u, .t-u, .u-u Alternative mRNAs features, proteins, introns, exons, sequences Expression Tissue Function, regulation, related genes DCI

To mine knowledge about the gene, please click the 'Gene Summary' or the 'Function, regulation, related genes ' tab at the top of the page. The 'Gene Summary' page includes all we learnt about the gene, functional annotations of neighboring genes, maps, links to other sites and the bibliography. The 'Function, regulation, related genes ' page includes Diseases (D), Pathways, GO annotations, conserved domains (C), interactions (I) reference into function, and pointers to all genes with the same functional annotation.
To compare alternative variants, their summarized annotations, predicted proteins, introns and exons, or to access any sequence, click the 'Alternative mRNAs features' tab. To see a specific mRNA variant diagram, sequence and annotation, click the variant name in the 'mRNA' tab. To examine expression data from all cDNAs clustered in this gene by AceView, click the 'Expression tissue'.

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