CFI (complement factor I)

Gene

• Entrez ID: 3426
• Gene name: Complement factor I
• Gene symbol: CFI
• Synonyms: AHUS3, ARMD13, C3BINA, C3b-INA, FI, IF, KAF
• Chromosome: 4
• Chromosome location: 4q25
• Summary: This gene encodes a serine proteinase that is essential for regulating the complement cascade. The encoded preproprotein is cleaved to produce both heavy and light chains, which are linked by disulfide bonds to form a heterodimeric glycoprotein. This hete

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs112534524	C>G,T	Pathogenic, likely-benign	Missense variant, coding sequence variant, non coding transcript variant
rs121964912	T>A,C	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant, intron variant
rs121964913	G>A,T	Risk-factor	Synonymous variant, coding sequence variant, stop gained, non coding transcript variant, intron variant
rs121964914	T>A,C	Risk-factor	Coding sequence variant, genic downstream transcript variant, missense variant, downstream transcript variant, non coding transcript variant, intron variant
rs121964915	C>A,T	Risk-factor	Coding sequence variant, genic downstream transcript variant, stop gained, missense variant, downstream transcript variant, non coding transcript variant, intron variant
rs121964916	C>A,T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs121964917	G>A	Risk-factor	Missense variant, coding sequence variant, non coding transcript variant
rs121964918	C>T	Risk-factor	Coding sequence variant, genic downstream transcript variant, missense variant, downstream transcript variant, non coding transcript variant, intron variant
rs141853578	C>T	Uncertain-significance, risk-factor	Missense variant, intron variant, non coding transcript variant, coding sequence variant
rs200419722	C>T	Likely-pathogenic	Coding sequence variant, intron variant, non coding transcript variant, missense variant
rs368615806	G>A	Likely-pathogenic	Coding sequence variant, stop gained, 5 prime UTR variant, non coding transcript variant
rs371432629	C>T	Risk-factor	Coding sequence variant, intron variant, non coding transcript variant, missense variant
rs752671716	G>A,T	Likely-pathogenic	Synonymous variant, coding sequence variant, stop gained, non coding transcript variant, intron variant
rs758049059	->AT	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant, intron variant
rs772044176	T>C	Likely-pathogenic	Coding sequence variant, non coding transcript variant, intron variant, missense variant
rs886043418	AT>-	Pathogenic	Coding sequence variant, intron variant, non coding transcript variant, frameshift variant
rs1292929833	G>A	Likely-pathogenic	Coding sequence variant, missense variant, intron variant, non coding transcript variant
rs1553915717	G>C	Pathogenic	Intron variant, coding sequence variant, missense variant, non coding transcript variant
rs1579173999	C>G	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018438	hsa-miR-335-5p	Microarray	18185580
MIRT025158	hsa-miR-181a-5p	Microarray	17612493
MIRT029753	hsa-miR-26b-5p	Microarray	19088304

Transcription factors

Transcription factor	Regulation	Reference
NFKB1	Activation	10630630
RELA	Activation	10630630

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004252	Function	Serine-type endopeptidase activity	IEA
GO:0005044	Function	Scavenger receptor activity	IEA
GO:0005515	Function	Protein binding	IPI	16237761
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	HDA	16502470
GO:0006508	Process	Proteolysis	IEA
GO:0006897	Process	Endocytosis	IEA
GO:0006958	Process	Complement activation, classical pathway	IEA
GO:0016020	Component	Membrane	IEA
GO:0016032	Process	Viral process	IEA
GO:0030449	Process	Regulation of complement activation	TAS
GO:0045087	Process	Innate immune response	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145

Other IDs

• MIM: 217030
• HGNC: 5394
• e!Ensembl: ENSG00000205403

Protein

• UniProt ID: P05156
• Protein name: Complement factor I (EC 3.4.21.45) (C3B/C4B inactivator) [Cleaved into: Complement factor I heavy chain; Complement factor I light chain]
• Protein function: Trypsin-like serine protease that plays an essential role in regulating the immune response by controlling all complement pathways. Inhibits these pathways by cleaving three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chai
• PDB: 2XRC, 5O32
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00530	SRCR	117 → 215	Scavenger receptor cysteine-rich domain	Domain
  PF00057	Ldl_recept_a	223 → 256	Low-density lipoprotein receptor domain class A	Repeat
  PF00057	Ldl_recept_a	257 → 293	Low-density lipoprotein receptor domain class A	Repeat
  PF00089	Trypsin	340 → 569	Trypsin	Domain

• Sequence:

  MKLLHVFLLFLCFHLRFCKVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIEGTCV
  CKLPYQCPKNGTAVCATNRRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGN
  TDSEGIVEVKLVDQDKTMFICKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTE
  CLHVHCRGLETSLAECTFTKRRTMGYQDFADVVCYTQKADSPMDDFFQCVNGKYISQMKA
  CDGINDCGDQSDELCCKACQGKGFHCKSGVCIPSQYQCNGEVDCITGEDEVGCAGFASVT
  QEETEILTADMDAERRRIKSLLPKLSCGVKNRMHIRRKRIVGGKRAQLGDLPWQVAIKDA
  SGITCGGIYIGGCWILTAAHCLRASKTHRYQIWTTVVDWIHPDLKRIVIEYVDRIIFHEN
  YNAGTYQNDIALIEMKKDGNKKDCELPRSIPACVPWSPYLFQPNDTCIVSGWGREKDNER
  VFSLQWGEVKLISNCSKFYGNRFYEKEMECAGTYDGSIDACKGDSGGPLVCMDANNVTYV
  WGVVSWGENCGKPEFPGVYTKVANYFDWISYHVGRPFISQYNV

• Sequence length: 583

Pathways

KEGG:

Complement and coagulation cascades
Staphylococcus aureus infection

Reactome:

Regulation of Complement cascade

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Arthritis	Arthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470
Complement component deficiency	Complement deficiency disease, Complement Factor I (C3 inactivator) deficiency, Immunodeficiency with factor I anomaly	rs387906509, rs1467298230, rs1022194067, rs774370086, rs121964922, rs372345940, rs121913052, rs121913053, rs460897, rs121913054, rs121913056, rs121913058, rs796052138, rs41286844, rs121909592, rs34000044, rs121909594, rs121909587, rs121909588, rs387906554, rs587776846, rs2135727106, rs460184, rs775967055, rs398122811, rs140813121, rs146187042, rs372968576, rs398122867, rs398122868, rs9332736, rs398124644, rs142881576, rs531103546, rs764871530, rs778518669, rs139491301, rs61469168, rs1554718962, rs1565789104, rs1579848888, rs779723422, rs867425110, rs770367814	24142231, 12562389, 25988862, 17018561, 8613545, 24142231
Doyne honeycomb retinal dystrophy	DOYNE HONEYCOMB RETINAL DYSTROPHY	rs121434491, rs281865373	25986072
Glomerulonephritis	Glomerulonephritis	rs778043831
Hemolytic uremic syndrome	Hemolytic-Uremic Syndrome, Atypical Hemolytic Uremic Syndrome, Atypical hemolytic uremic syndrome with complement gene abnormality	rs398124292, rs121964913, rs121964914, rs121964915, rs121918667, rs33972593, rs117905900, rs121909748, rs460897, rs796052136, rs121913055, rs796052137, rs121913060, rs121913063, rs1558056827, rs1255421232, rs1441937053, rs121909590, rs121909583, rs121909584, rs121909586, rs460184, rs104886189, rs312262694, rs312262697, rs312262698, rs312262696, rs138924661, rs869312973, rs886039869, rs886039868, rs886043418, rs1057516191, rs1131690796, rs1553273733, rs1553251787, rs777787526, rs769742294, rs775015499, rs1555599211, rs1558162157, rs1600410451, rs368615806, rs1573026975, rs1573087200, rs1571588257, rs147972030, rs1906529223, rs749415630, rs1573076111, rs1300996807, rs1571616755, rs1571617647, rs1579173999, rs1599510478
Hypertension	Hypertensive disease	rs13306026, rs13333226
Hypofibrinogenemia	Hypofibrinogenemia	rs121913087, rs121913088, rs587776837, rs121909616, rs121909625, rs121909608, rs121909607, rs146387238, rs1578795296, rs1214070111, rs776817952, rs762964798, rs121909606, rs1414035000, rs1310452604
Age-related macular degeneration	Age related macular degeneration, MACULAR DEGENERATION, AGE-RELATED, 13, NON RARE IN EUROPE: Age-related macular degeneration	rs2133900556, rs199474657, rs2274700, rs1410996, rs61750120, rs1800728, rs62654397, rs61749423, rs61751412, rs61749439, rs61751398, rs61752417, rs62645946, rs1801269, rs62646860, rs61750142, rs61750145, rs61750152, rs61751377, rs61753029, rs61751407, rs61751389, rs61750645, rs61750648, rs879255520, rs752147871, rs886044750, rs886044749, rs746541266, rs756840095, rs886044725, rs749526785, rs1057518955, rs1057518767, rs371489809, rs1064793014, rs1571264574, rs1659524475	26691988, 24036952, 23685748, 23685748, 24142231
Renal insufficiency	Renal Insufficiency	rs1596536873
Vasculitis	Vasculitis, Vasculitis, Leukocytoclastic, Cutaneous	rs376785840, rs587777240, rs200930463, rs587777241, rs77563738, rs202134424, rs148936893, rs587777242, rs775440641, rs770689762, rs45511697, rs139750129, rs756881285, rs747774101, rs1568966771, rs766602945, rs1601419986, rs1489114116, rs754904956, rs755007390, rs368615054	25988862

Unknown
Disease name	Disease term	dbSNP ID	References
C3 glomerulopathy	C3 glomerulopathy	rs318240755, rs368209619, rs140215003, rs9427662, rs34533956, rs57960694, rs565457964, rs375481393, rs201084185, rs16840956, rs61745675, rs147791058, rs147488267, rs7532068, rs114023763, rs140691305, rs139017763, rs35662416, rs751010317, rs185709089, rs772780646, rs771972507, rs12097550, rs143140599, rs41306229, rs141358257, rs556270179, rs550747814	27458560
Disseminated intravascular coagulation	Disseminated Intravascular Coagulation
Drusen	Drusen, Drusen, Radial, Autosomal Dominant, Familial drusen		25986072
Eclampsia	Eclampsia
Exudative macular degeneration	Exudative age-related macular degeneration, exudative macular degeneration		26691988
Fibrinogen deficiency	Fibrinogen Deficiency		24142231
Geographic atrophy	Geographic Atrophy		26691988
Hellp syndrome	HELLP Syndrome		18658028, 22594569
Leukocytoclastic vasculitis	Leukocytoclastic vasculitis		25988862
Malattia leventinese	Malattia Leventinese		25986072
Maternal hypertension	Maternal hypertension
Microangiopathic hemolytic anemia	Microangiopathic hemolytic anemia
Otitis media	Recurrent otitis media	rs601338, rs1047781, rs1800028
Pleural effusion	Pleural effusion disorder
Pyelonephritis	Pyelonephritis
Sinusitis	Sinusitis, Recurrent sinusitis