C1R (complement C1r)

Gene

• Entrez ID: 715
• Gene name: Complement C1r
• Gene symbol: C1R
• Synonyms (NCBI Gene): EDS8, EDSPD1
• Chromosome: 12
• Chromosome location: 12p13.31
• 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,

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs760277934	C>G,T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs769707492	G>A,C,T	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained, synonymous variant, missense variant
rs1057515579	A>G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1057518643	T>C	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1057518645	C>A	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1057518646	GCACTTGATGA>TGTCC	Likely-pathogenic, pathogenic	Inframe indel, coding sequence variant
rs1057519025	GA>AT	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1057519026	C>T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1057519576	T>C	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1057519577	A>G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1057519578	C>G,T	Likely-pathogenic, pathogenic	Stop gained, missense variant, coding sequence variant
rs1057519579	G>C	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1057519580	GTAGTACTGGATACGG>TATTACATGA	Likely-pathogenic, pathogenic	Inframe indel, coding sequence variant
rs1060499554	A>G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1555164437	C>T	Likely-pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT630739	hsa-miR-6817-3p	HITS-CLIP	23824327
MIRT630738	hsa-miR-518c-5p	HITS-CLIP	23824327
MIRT630737	hsa-miR-326	HITS-CLIP	23824327
MIRT630736	hsa-miR-330-5p	HITS-CLIP	23824327
MIRT630735	hsa-miR-6764-3p	HITS-CLIP	23824327
MIRT630734	hsa-miR-6824-3p	HITS-CLIP	23824327
MIRT630733	hsa-miR-3191-5p	HITS-CLIP	23824327
MIRT630732	hsa-miR-3692-3p	HITS-CLIP	23824327
MIRT630739	hsa-miR-6817-3p	HITS-CLIP	23824327
MIRT630738	hsa-miR-518c-5p	HITS-CLIP	23824327
MIRT630737	hsa-miR-326	HITS-CLIP	23824327
MIRT630736	hsa-miR-330-5p	HITS-CLIP	23824327
MIRT630735	hsa-miR-6764-3p	HITS-CLIP	23824327
MIRT630734	hsa-miR-6824-3p	HITS-CLIP	23824327
MIRT630733	hsa-miR-3191-5p	HITS-CLIP	23824327
MIRT630732	hsa-miR-3692-3p	HITS-CLIP	23824327
MIRT630739	hsa-miR-6817-3p	HITS-CLIP	23824327
MIRT630738	hsa-miR-518c-5p	HITS-CLIP	23824327
MIRT630737	hsa-miR-326	HITS-CLIP	23824327
MIRT630736	hsa-miR-330-5p	HITS-CLIP	23824327
MIRT630735	hsa-miR-6764-3p	HITS-CLIP	23824327
MIRT630734	hsa-miR-6824-3p	HITS-CLIP	23824327
MIRT630733	hsa-miR-3191-5p	HITS-CLIP	23824327
MIRT630732	hsa-miR-3692-3p	HITS-CLIP	23824327
MIRT630739	hsa-miR-6817-3p	HITS-CLIP	23824327
MIRT630738	hsa-miR-518c-5p	HITS-CLIP	23824327
MIRT630737	hsa-miR-326	HITS-CLIP	23824327
MIRT630736	hsa-miR-330-5p	HITS-CLIP	23824327
MIRT630735	hsa-miR-6764-3p	HITS-CLIP	23824327
MIRT630734	hsa-miR-6824-3p	HITS-CLIP	23824327
MIRT630733	hsa-miR-3191-5p	HITS-CLIP	23824327
MIRT630732	hsa-miR-3692-3p	HITS-CLIP	23824327
MIRT842504	hsa-miR-129-5p	CLIP-seq
MIRT842505	hsa-miR-140-5p	CLIP-seq
MIRT842506	hsa-miR-3545-5p	CLIP-seq
MIRT842507	hsa-miR-3692	CLIP-seq
MIRT842508	hsa-miR-3976	CLIP-seq
MIRT842509	hsa-miR-4460	CLIP-seq
MIRT842510	hsa-miR-4727-3p	CLIP-seq
MIRT842511	hsa-miR-633	CLIP-seq
MIRT842504	hsa-miR-129-5p	CLIP-seq
MIRT842507	hsa-miR-3692	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001905	Process	Activation of membrane attack complex	IDA	18204047
GO:0002376	Process	Immune system process	IEA
GO:0004252	Function	Serine-type endopeptidase activity	EXP	11823416
GO:0004252	Function	Serine-type endopeptidase activity	IBA
GO:0004252	Function	Serine-type endopeptidase activity	IDA	6254570, 6271784, 11445589, 11673533, 17996945, 20178990
GO:0004252	Function	Serine-type endopeptidase activity	IEA
GO:0004252	Function	Serine-type endopeptidase activity	TAS	2834284
GO:0005509	Function	Calcium ion binding	IDA	20178990
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	2387866, 12788922, 17996945, 28514442, 28742139, 31749804, 33961781
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005602	Component	Complement component C1 complex	IDA	2988513, 6249812, 6952210, 23650384, 34155115
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	20178990
GO:0005615	Component	Extracellular space	IEA
GO:0006508	Process	Proteolysis	IEA
GO:0006955	Process	Immune response	TAS	737019
GO:0006956	Process	Complement activation	IDA	26841934, 30111885, 37852260
GO:0006956	Process	Complement activation	IEA
GO:0006958	Process	Complement activation, classical pathway	IDA	3897448, 6906228, 9422791, 11673533, 16169853, 18204047
GO:0006958	Process	Complement activation, classical pathway	IDA	6249812, 6254570, 6271784, 11673533, 17996945, 20178990, 23650384, 34155115
GO:0006958	Process	Complement activation, classical pathway	IEA
GO:0006958	Process	Complement activation, classical pathway	TAS
GO:0008228	Process	Opsonization	IDA	3897448, 8538770
GO:0008233	Function	Peptidase activity	IEA
GO:0008236	Function	Serine-type peptidase activity	IEA
GO:0008236	Function	Serine-type peptidase activity	TAS	2834284
GO:0009986	Component	Cell surface	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0031638	Process	Zymogen activation	IBA
GO:0031638	Process	Zymogen activation	IDA	11673533, 16169853
GO:0031638	Process	Zymogen activation	IDA	6271784, 11673533, 20178990
GO:0031638	Process	Zymogen activation	IEA
GO:0031640	Process	Killing of cells of another organism	IDA	30552328
GO:0042802	Function	Identical protein binding	IPI	20970424, 31749804
GO:0045087	Process	Innate immune response	IEA
GO:0051604	Process	Protein maturation	IDA	6906228, 16169853, 18204047
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0072562	Component	Blood microparticle	HDA	22516433
GO:0072562	Component	Blood microparticle	IBA
GO:0106139	Component	Symbiont cell surface	IDA	34155115
GO:0140313	Function	Molecular sequestering activity	EXP	20178990

Other IDs

• MIM: 613785
• HGNC: 1246
• e!Ensembl: ENSG00000159403

Protein

• UniProt ID: P00736
• Protein name: Complement C1r subcomponent (EC 3.4.21.41) (Complement component 1 subcomponent r) [Cleaved into: Complement C1r subcomponent heavy chain (Complement C1r subcomponent chain A); Complement C1r subcomponent light chain (Complement C1r subcomponent chain B)]
• Protein function: Serine protease component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strength
• PDB: 1APQ, 1GPZ, 1MD7, 1MD8, 2QY0, 6F1C, 6F1D, 6F1H, 6F39, 9EKD, 9EKE
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00431	CUB	20 → 131	CUB domain	Domain
  PF14670	FXa_inhibition	154 → 189		Domain
  PF00431	CUB	193 → 302	CUB domain	Domain
  PF00084	Sushi	309 → 371	Sushi repeat (SCR repeat)	Domain
  PF00084	Sushi	376 → 447	Sushi repeat (SCR repeat)	Domain
  PF00089	Trypsin	464 → 697	Trypsin	Domain

• Sequence:

  MWLLYLLVPALFCRAGGSIPIPQKLFGEVTSPLFPKPYPNNFETTTVITVPTGYRVKLVF
  QQFDLEPSEGCFYDYVKISADKKSLGRFCGQLGSPLGNPPGKKEFMSQGNKMLLTFHTDF
  SNEENGTIMFYKGFLAYYQAVDLDECASRSKSGEEDPQPQCQHLCHNYVGGYFCSCRPGY
  ELQEDTHSCQAECSSELYTEASGYISSLEYPRSYPPDLRCNYSIRVERGLTLHLKFLEPF
  DIDDHQQVHCPYDQLQIYANGKNIGEFCGKQRPPDLDTSSNAVDLLFFTDESGDSRGWKL
  RYTTEIIKCPQPKTLDEFTIIQNLQPQYQFRDYFIATCKQGYQLIEGNQVLHSFTAVCQD
  DGTWHRAMPRCKIKDCGQPRNLPNGDFRYTTTMGVNTYKARIQYYCHEPYYKMQTRAGSR
  ESEQGVYTCTAQGIWKNEQKGEKIPRCLPVCGKPVNPVEQRQRIIGGQKAKMGNFPWQVF
  TNIHGRGGGALLGDRWILTAAHTLYPKEHEAQSNASLDVFLGHTNVEELMKLGNHPIRRV
  SVHPDYRQDESYNFEGDIALLELENSVTLGPNLLPICLPDNDTFYDLGLMGYVSGFGVME
  EKIAHDLRFVRLPVANPQACENWLRGKNRMDVFSQNMFCAGHPSLKQDACQGDSGGVFAV
  RDPNTDRWVATGIVSWGIGCSRGYGFYTKVLNYVDWIKKEMEEED

• Sequence length: 705

Pathways

KEGG:

Phagosome
Complement and coagulation cascades
Pertussis
Staphylococcus aureus infection
Coronavirus disease - COVID-19
Systemic lupus erythematosus

Reactome:

Initial triggering of complement
Classical antibody-mediated complement activation
Regulation of Complement cascade

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Ehlers-Danlos syndrome	Likely pathogenic	rs1938242419	RCV001248812
Ehlers-Danlos syndrome, periodontal type 1	Likely pathogenic; Pathogenic	rs1057518645, rs760277934, rs769707492, rs1057515579, rs1057518646, rs1057518643, rs1057519025, rs1057519580, rs1057519579, rs1057519578, rs1057519577, rs1057519576, rs1060499554, rs1938056582	RCV003154094 RCV000258068 RCV000258069 RCV000258072 RCV000258067 RCV000258071 RCV000258064 RCV000412647 RCV000417044 RCV000417063 RCV000417050 RCV000417066 RCV000417060 RCV000417057 RCV001250191
Ehlers-Danlos syndrome, periodontal type 2	Pathogenic	rs1057518645, rs760277934, rs769707492, rs1057515579, rs1057518646, rs1057518643, rs1057519025, rs1057519580, rs1057519579, rs1057519578, rs1057519577, rs1057519576, rs1060499554	RCV000755118 RCV000755113 RCV000755116 RCV000755112 RCV000755115 RCV000755110 RCV000755109 RCV000755121 RCV000755120 RCV000755119 RCV000755117 RCV000755114 RCV000755122

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
C1R-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity; Uncertain significance	rs201255383, rs146478898, rs189155429, rs150953301, rs200539827, rs149665060, rs200899486, rs751803218, rs570489350, rs144141261, rs202082509, rs2539627395, rs367785162, rs377326804, rs752795803	RCV004756210 RCV003921189 RCV003921353 RCV003943332 RCV004731510 RCV003417082 RCV003402679 RCV003896484 RCV003904734 RCV003923881 RCV003904214 RCV003964540 RCV003933835 RCV003944578 RCV003962270
See cases	Uncertain significance	rs774424047	RCV004584553
Vascular dementia	Uncertain significance; Conflicting classifications of pathogenicity	rs769328977, rs139531404	RCV002051770 RCV001263175

Associations from Text Mining
Disease Name	Relationship Type	References
Alzheimer Disease	Associate	37307028, 40037332
Ataxia	Associate	30535813
Atrial Fibrillation	Associate	36341343
Bipolar Disorder	Associate	39616737
Blood Coagulation Disorders	Associate	27613243
Carcinoma Hepatocellular	Inhibit	34813686
Carcinoma Squamous Cell	Associate	31049937
Cerebral Infarction	Associate	34912031
Cerebral Small Vessel Diseases	Associate	30535813
Cognition Disorders	Associate	30535813
Coronavirus Infections	Associate	35726234
COVID 19	Associate	35726234
Dystonic Disorders	Associate	31049937
Ehlers Danlos Syndrome	Associate	31921203
Ehlers Danlos Syndrome Type VIII	Associate	27745832, 30535813, 31749804, 31921203, 33498938, 36960056
Epidermolysis Bullosa Dystrophica	Associate	31049937
Glioblastoma	Associate	33009892, 35726234
Glioma	Associate	33009892
Hyperthyroidism	Associate	32575434
Hypoxia Brain	Associate	33009892
Immunologic Deficiency Syndromes	Associate	27613243
Inflammation	Associate	36596079, 39616737
Keratosis Actinic	Inhibit	31049937
Leukoencephalopathies	Associate	30535813
Lupus Erythematosus Systemic	Associate	28544690, 32576231
Lymphatic Metastasis	Associate	33658651
Lymphoma Non Hodgkin	Associate	27745832
Muscular Dystrophy Duchenne	Associate	36596079
Myocardial Infarction	Associate	32389013
Neoplasms	Associate	31049937
Neoplasms	Inhibit	34813686
Neoplasms Squamous Cell	Stimulate	31049937
Osteoarthritis	Associate	29257293, 34208590
Periodic fever familial autosomal dominant	Associate	28544690
Periodontitis	Associate	31921203
Schizophrenia	Associate	39616737
Scleroderma Systemic	Associate	39684939
Seizures	Associate	30535813
Squamous Cell Carcinoma of Head and Neck	Stimulate	26552850