C1R complement C1r [Homo sapiens (human)] - Gene

Summary

Official Symbol: C1Rprovided by HGNC
Official Full Name: complement C1rprovided by HGNC
Primary source: HGNC:HGNC:1246
See related: Ensembl:ENSG00000159403 MIM:613785; AllianceGenome:HGNC:1246
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: EDS8; EDSPD1
Summary: This gene encodes a member of the peptidase S1 protein family. The encoded protein is a proteolytic subunit in the complement system C1 complex. The complement system acts as a mediator in the innate immune response by ultimately triggering phagocytosis, inflammation, and rupturing the bacterial cell wall. Mutations in this gene are associated with Ehlers-Danlos Syndrome. [provided by RefSeq, Dec 2018]
Expression: Broad expression in liver (RPKM 563.3), gall bladder (RPKM 285.8) and 20 other tissues See more
Orthologs: all
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Genomic context

Location:: 12p13.31

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (7080219..7092445, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (7093689..7105531, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (7187523..7245041, complement)

Chromosome 12 - NC_000012.12 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?

Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.
Title: Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.
C1r Upregulates Production of Matrix Metalloproteinase-13 and Promotes Invasion of Cutaneous Squamous Cell Carcinoma.
Title: C1r Upregulates Production of Matrix Metalloproteinase-13 and Promotes Invasion of Cutaneous Squamous Cell Carcinoma.
A familial case of periodontal Ehlers-Danlos syndrome lacking skin extensibility and joint hypermobility with a missense mutation in C1R.
Title: A familial case of periodontal Ehlers-Danlos syndrome lacking skin extensibility and joint hypermobility with a missense mutation in C1R.
C1R, CCL2, and TNFRSF1A Genes in Coronavirus Disease-COVID-19 Pathway Serve as Novel Molecular Biomarkers of GBM Prognosis and Immune Infiltration.
Title: C1R, CCL2, and TNFRSF1A Genes in Coronavirus Disease-COVID-19 Pathway Serve as Novel Molecular Biomarkers of GBM Prognosis and Immune Infiltration.
C1q binding to surface-bound IgG is stabilized by C1r2s2 proteases.
Title: C1q binding to surface-bound IgG is stabilized by C1r(2)s(2) proteases.
C1R Mutations Trigger Constitutive Complement 1 Activation in Periodontal Ehlers-Danlos Syndrome.
Title: C1R Mutations Trigger Constitutive Complement 1 Activation in Periodontal Ehlers-Danlos Syndrome.
periodontal Ehlers-Danlos syndrome caused by missense mutations in C1R is consistently associated with a leukoencephalopathy
Title: Periodontal Ehlers-Danlos syndrome is associated with leukoencephalopathy.
The serine protease domains of C1r and C1s are at the periphery of the C1r2s2 tetramer both when alone or within the nonactivated C1 complex. The C1 complex adopts a conformation incompatible with intramolecular activation of C1. Instead, intermolecular proteolytic activation between neighboring C1 complexes bound to a complement-activating surface occurs. Many structurally unrelated molecular patterns can activate C1.
Title: Structure and activation of C1, the complex initiating the classical pathway of the complement cascade.
We identified a novel, homozygous, loss-of-function mutation (p.Pro445Leufs*11) in the C1R gene. Using the Sanger method of DNA sequencing in 14 family members, we confirmed the presence of the mutation in 4 patients with early-onset systemic lupus erythematosus and in an asymptomatic 9-year-old girl. Complement levels were low in sera from patients with truncated C1r protein.
Title: Brief Report: Deficiency of Complement 1r Subcomponent in Early-Onset Systemic Lupus Erythematosus: The Role of Disease-Modifying Alleles in a Monogenic Disease.
Periodontal Ehlers-Danlos Syndrome in at least the great majority of cases results from specific classes of heterozygous mutations in C1R and C1S.
Title: Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement.

Submit: New GeneRIF Correction See all GeneRIFs (25)

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
Ehlers-Danlos syndrome, periodontal type 1 MedGen: C4551499 OMIM: 130080 GeneReviews: Periodontal Ehlers-Danlos Syndrome	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH75712 (e-PCR)
- UniSTS:92442

G32495 (e-PCR)
- UniSTS:117080

C1R_1615 (e-PCR)
- UniSTS:463242

GDB:251487 (e-PCR)
- UniSTS:156307

RH80031 (e-PCR)
- UniSTS:91103

RH17663 (e-PCR)
- UniSTS:71396

A009F01 (e-PCR)
- UniSTS:46315

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables molecular sequestering activity	EXP Inferred from Experiment more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	EXP Inferred from Experiment more info	PubMed
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type peptidase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in complement activation, classical pathway	TAS Traceable Author Statement more info
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in zymogen activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in zymogen activation	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in blood microparticle	HDA more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: complement C1r subcomponent

Names: complement component 1, r subcomponent

NP_001341275.1

EC 3.4.21.41

NP_001724.4

EC 3.4.21.41

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_062465.1 RefSeqGene

Range

5163..16620

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1321

mRNA and Protein(s)

NM_001354346.2 → NP_001341275.1 complement C1r subcomponent isoform 2 preproprotein

Status: REVIEWED

Source sequence(s)

AC233309, AK298445, BC035220

Consensus CDS

CCDS86272.1

UniProtKB/Swiss-Prot

A6NJQ8, P00736, Q68D77, Q8J012

UniProtKB/TrEMBL

B4DPQ0, F5GZR1

Related

ENSP00000444271.3, ENST00000536053.6

Conserved Domains (5) summary

smart00020
Location:477 → 711

Tryp_SPc; Trypsin-like serine protease

smart00042
Location:41 → 152

CUB; Domain first found in C1r, C1s, uEGF, and bone morphogenetic protein

pfam00431
Location:207 → 316

CUB; CUB domain

pfam00084
Location:323 → 385

Sushi; Sushi repeat (SCR repeat)

pfam14670
Location:175 → 203

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001733.7 → NP_001724.4 complement C1r subcomponent isoform 1 preproprotein

Status: REVIEWED

Source sequence(s)

BC035220, M14058

Consensus CDS

CCDS81658.1

UniProtKB/Swiss-Prot

A6NJQ8, P00736, Q68D77, Q8J012

UniProtKB/TrEMBL

A0A3B3ISR2

Related

ENSP00000497341.1, ENST00000647956.2

Conserved Domains (5) summary

smart00020
Location:463 → 697

Tryp_SPc; Trypsin-like serine protease

smart00042
Location:27 → 138

CUB; Domain first found in C1r, C1s, uEGF, and bone morphogenetic protein

pfam00431
Location:193 → 302

CUB; CUB domain

pfam00084
Location:309 → 371

Sushi; Sushi repeat (SCR repeat)

pfam14670
Location:161 → 189

FXa_inhibition; Coagulation Factor Xa inhibitory site