CFI complement factor I [Homo sapiens (human)] - Gene

Summary

Official Symbol: CFIprovided by HGNC
Official Full Name: complement factor Iprovided by HGNC
Primary source: HGNC:HGNC:5394
See related: Ensembl:ENSG00000205403 MIM:217030; AllianceGenome:HGNC:5394
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FI; IF; KAF; AHUS3; ARMD13; C3BINA; C3b-INA
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 heterodimer can cleave and inactivate the complement components C4b and C3b, and it prevents the assembly of the C3 and C5 convertase enzymes. Defects in this gene cause complement factor I deficiency, an autosomal recessive disease associated with a susceptibility to pyogenic infections. Mutations in this gene have been associated with a predisposition to atypical hemolytic uremic syndrome, a disease characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Primary glomerulonephritis with immune deposits and age-related macular degeneration are other conditions associated with mutations of this gene. [provided by RefSeq, Dec 2015]
Expression: Biased expression in liver (RPKM 171.8), kidney (RPKM 63.6) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q25

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (109730982..109801999, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (113031939..113104052, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (110652138..110723155, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CNS Inflammation as the First Sign of Complement Factor I Deficiency.
Title: CNS Inflammation as the First Sign of Complement Factor I Deficiency: A Severe Myelitis Treated With Intense Immunotherapy and Eculizumab.
Complement factor I: Regulatory nexus, driver of immunopathology, and therapeutic.
Title: Complement factor I: Regulatory nexus, driver of immunopathology, and therapeutic.
Mutations in atypical hemolytic uremic syndrome provide evidence for the role of calcium in complement factor I.
Title: Mutations in atypical hemolytic uremic syndrome provide evidence for the role of calcium in complement factor I.
A novel method for real-time analysis of the complement C3b:FH:FI complex reveals dominant negative CFI variants in age-related macular degeneration.
Title: A novel method for real-time analysis of the complement C3b:FH:FI complex reveals dominant negative CFI variants in age-related macular degeneration.
Functional analysis of rare genetic variants in complement factor I in advanced age-related macular degeneration.
Title: Functional analysis of rare genetic variants in complement factor I in advanced age-related macular degeneration.
An assessment of prevalence of Type 1 CFI rare variants in European AMD, and why lack of broader genetic data hinders development of new treatments and healthcare access.
Title: An assessment of prevalence of Type 1 CFI rare variants in European AMD, and why lack of broader genetic data hinders development of new treatments and healthcare access.
Prevalence and phenotype associations of complement factor I mutations in geographic atrophy.
Title: Prevalence and phenotype associations of complement factor I mutations in geographic atrophy.
Functional Analysis of Variants in Complement Factor I Identified in Age-Related Macular Degeneration and Atypical Hemolytic Uremic Syndrome.
Title: Functional Analysis of Variants in Complement Factor I Identified in Age-Related Macular Degeneration and Atypical Hemolytic Uremic Syndrome.
Effect of rare coding variants in the CFI gene on Factor I expression levels.
Title: Effect of rare coding variants in the CFI gene on Factor I expression levels.
Complement family member CFI polymorphisms and AMD susceptibility from a comprehensive analysis.
Title: Complement family member CFI polymorphisms and AMD susceptibility from a comprehensive analysis.

Submit: New GeneRIF Correction See all GeneRIFs (89)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Age related macular degeneration 13 MedGen: C3809523 OMIM: 615439 GeneReviews: Not available	Compare labs
Atypical hemolytic-uremic syndrome with I factor anomaly MedGen: C2752039 OMIM: 612923 GeneReviews: Genetic Atypical Hemolytic-Uremic Syndrome	Compare labs
Factor I deficiency MedGen: C3463916 OMIM: 610984 GeneReviews: C3 Glomerulopathy	Compare labs

EBI GWAS Catalog

Description
Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits. EBI GWAS Catalog EBI GWAS CatalogPubMed
Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seven new loci associated with age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See Variation Viewer (GRCh37.p13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-19821 (e-PCR)
- UniSTS:1792

D4S3129 (e-PCR)
- UniSTS:66312

SHGC-19817 (e-PCR)
- UniSTS:11540

SHGC-19819 (e-PCR)
- UniSTS:33368

G33805 (e-PCR)
- UniSTS:3723

SHGC-59752 (e-PCR)
- UniSTS:31986

SHGC4-316 (e-PCR)
- UniSTS:75259

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in complement activation, classical pathway	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: complement factor I

Names: C3B/C4B inactivator; C3b-inactivator; Konglutinogen-activating factor; complement component I; complement control protein factor I; complement factor I heavy chain; light chain of factor I

NP_000195.3

EC 3.4.21.45

NP_001304986.2

EC 3.4.21.45

NP_001317964.1

EC 3.4.21.45

NP_001362207.1

EC 3.4.21.45

NP_001362208.1

EC 3.4.21.45

NP_001362209.1

EC 3.4.21.45

NP_001362210.1

EC 3.4.21.45

NP_001362211.1

EC 3.4.21.45

NP_001362212.1

EC 3.4.21.45

NP_001362213.1

EC 3.4.21.45

XP_006714273.1

EC 3.4.21.45

XP_011530222.1

EC 3.4.21.45

XP_047271609.1

EC 3.4.21.45

XP_047271610.1

EC 3.4.21.45

XP_054205914.1

EC 3.4.21.45

XP_054205915.1

EC 3.4.21.45

XP_054205916.1

EC 3.4.21.45

XP_054205917.1

EC 3.4.21.45

XP_054205918.1

EC 3.4.21.45

XP_054205919.1

EC 3.4.21.45

XP_054205920.1

EC 3.4.21.45

XP_054205921.1

EC 3.4.21.45

XP_054205922.1

EC 3.4.21.45

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007569.1 RefSeqGene

Range

4807..66294

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_48

mRNA and Protein(s)

NM_000204.5 → NP_000195.3 complement factor I isoform 2 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes isoform 2.

Source sequence(s)

AC126283

Consensus CDS

CCDS34049.1

UniProtKB/Swiss-Prot

O60442, P05156

UniProtKB/TrEMBL

A8K3L0

Related

ENSP00000378130.2, ENST00000394634.7

Conserved Domains (5) summary

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:340 → 572

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A
NM_001318057.2 → NP_001304986.2 complement factor I isoform 1 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (1) contains an alternate in-frame exon compared to variant 2. The encoded isoform (1) is longer than isoform 2.

Source sequence(s)

AC126283

Consensus CDS

CCDS82946.1

UniProtKB/TrEMBL

B4DRF2, E7ETH0

Related

ENSP00000378131.3, ENST00000394635.8

Conserved Domains (5) summary

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:348 → 580

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A
NM_001331035.2 → NP_001317964.1 complement factor I isoform 3 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon in the central coding region compared to variant 2. The encoded isoform (3) lacks a portion of the heavy chain compared to isoform 2.

Source sequence(s)

AK290625, BM955734, BX453590, DC392360, J02770, N63668

Consensus CDS

CCDS82945.1

UniProtKB/TrEMBL

A8K3L0, G3XAM2

Related

ENSP00000427438.1, ENST00000512148.5

Conserved Domains (7) summary

smart00020
Location:332 → 562

Tryp_SPc; Trypsin-like serine protease

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:333 → 565

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00530
Location:119 → 214

SRCR; Scavenger receptor cysteine-rich domain
NM_001375278.1 → NP_001362207.1 complement factor I isoform 4 preproprotein

Status: REVIEWED

Source sequence(s)

AC004067, AC126283

UniProtKB/TrEMBL

B4DRF2

Conserved Domains (5) summary

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:348 → 519

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A
NM_001375279.1 → NP_001362208.1 complement factor I isoform 5 preproprotein

Status: REVIEWED

Source sequence(s)

AC004067, AC126283

UniProtKB/TrEMBL

A8K3L0

Related

ENST00000695844.1

Conserved Domains (5) summary

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:340 → 511

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A
NM_001375280.1 → NP_001362209.1 complement factor I isoform 6 preproprotein

Status: REVIEWED

Source sequence(s)

AC004067, AC126283

UniProtKB/TrEMBL

A8K3L0

Conserved Domains (5) summary

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:333 → 504

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A
NM_001375281.1 → NP_001362210.1 complement factor I isoform 7 preproprotein

Status: REVIEWED

Source sequence(s)

AC004067, AC126283

UniProtKB/TrEMBL

A8K3L0

Related

ENST00000695845.1

Conserved Domains (5) summary

smart00020
Location:339 → 511

Tryp_SPc; Trypsin-like serine protease

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A
NM_001375282.1 → NP_001362211.1 complement factor I isoform 8 preproprotein

Status: REVIEWED

Source sequence(s)

AC004067, AC126283

UniProtKB/TrEMBL

A8K3L0

Conserved Domains (5) summary

smart00020
Location:332 → 504

Tryp_SPc; Trypsin-like serine protease

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A
NM_001375283.1 → NP_001362212.1 complement factor I isoform 9 preproprotein

Status: REVIEWED

Source sequence(s)

AC126283

UniProtKB/TrEMBL

A8K3L0

Conserved Domains (5) summary

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:321 → 553

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A
NM_001375284.1 → NP_001362213.1 complement factor I isoform 10

Status: REVIEWED

Source sequence(s)

AC126283

Conserved Domains (3) summary

cd00112
Location:21 → 53

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:137 → 369

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:54 → 90

Ldl_recept_a; Low-density lipoprotein receptor domain class A

RNA

NR_164671.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC126283
NR_164672.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC126283
NR_164673.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC126283

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

109730982..109801999 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011531920.3 → XP_011530222.1 complement factor I isoform X1

UniProtKB/TrEMBL

B4DRF2

Conserved Domains (8) summary

smart00020
Location:347 → 519

Tryp_SPc; Trypsin-like serine protease

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:348 → 519

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00530
Location:119 → 214

SRCR; Scavenger receptor cysteine-rich domain

pfam13900
Location:524 → 555

GVQW; Putative domain of unknown function
XM_047415653.1 → XP_047271609.1 complement factor I isoform X2
XM_047415654.1 → XP_047271610.1 complement factor I isoform X4
XM_006714210.5 → XP_006714273.1 complement factor I isoform X3

UniProtKB/TrEMBL

B4DRF2

Conserved Domains (7) summary

smart00020
Location:347 → 520

Tryp_SPc; Trypsin-like serine protease

smart00057
Location:43 → 108

FIMAC; factor I membrane attack complex

smart00202
Location:114 → 215

SR; Scavenger receptor Cys-rich

cd00112
Location:224 → 256

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:348 → 520

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:257 → 293

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00530
Location:119 → 214

SRCR; Scavenger receptor cysteine-rich domain