CR1

protein-coding

complement C3b/C4b receptor 1 (Knops blood group), the group of CD molecules|Sushi domain containing|Complement system regulators and receptors|Blood group antigens

Gene summary

This gene is a member of the receptors of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. The genome is polymorphic at this locus with allele-specific splice variants encoding different isoforms, based on the presence/absence of long homologous repeats (LHRs). The gene encodes a monomeric single-pass type I membrane glycoprotein found on erythrocytes, leukocytes, glomerular podocytes, and splenic follicular dendritic cells. The Knops blood group system is a system of antigens located on this protein. The protein mediates cellular binding to particles and immune complexes that have activated complement. Decreases in expression of this protein and/or mutations in this gene have been associated with gallbladder carcinomas, mesangiocapillary glomerulonephritis, systemic lupus erythematosus, sarcoidosis and Alzheimer's disease. Mutations in this gene have also been associated with a reduction in Plasmodium falciparum rosetting, conferring protection against severe malaria. [provided by RefSeq, May 2020]

MANE transcript

NM_000651.6

Inheritance

ClinVar variants

U:238B:42

Top phenotype

Blood group, Knops system

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr1:207,496,147-207,641,765

External References & Databases

Ensembl (ENSG00000203710)

Transcript & Mutation Effects

hg38 • Region Span ~145.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Blood group, Knops systemBG

Manifestation: Hematologic

Intervention: Hematologic

Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Refs: 11724985

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CR1 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 251

not providedTotal: 24

KNOPS BLOOD GROUP SYSTEMTotal: 6

CR1-related disorderTotal: 5

Malaria, susceptibility toTotal: 4

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

AnxietyTotal: 1

HypothyroidismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000651.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	13 clinvar	1 clinvar	18
missense			230 clinvar	24 clinvar	4 clinvar	258
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	238	37	5	280

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000651.6	RefSeq	NP_000642.3	47	MANE Select
ENST00000367049.9	Ensembl	ENSP00000356016.4	47	MANE Select
ENST00000367051.6	Ensembl	ENSP00000356018.1	39	Standard
ENST00000367051.7	Ensembl	ENSP00000356018.1	39	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Complement and coagulation cascades - Homo sapiens (human)
Legionellosis - Homo sapiens (human)
Malaria - Homo sapiens (human)
Tuberculosis - Homo sapiens (human)
Leishmaniasis - Homo sapiens (human)

Biological Process

complement receptor mediated signaling pathway
complement activation, classical pathway
regulation of complement activation
neutrophil degranulation
innate immune response

Molecular Function

virus receptor activity
complement component C3b binding
complement component C4b binding
complement component C4b receptor activity
complement component C3b receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane
cell surface
secretory granule membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367049
Coding exons: 47
Length: 144501
Individuals with no LoFs: 124394
Homozygous LoFs: 2
Heterozygous LoFs: 250
Defined: 124646
p: 0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.474	927	887	1.04	0.0000476	16327
Missense (PolyPhen)		249	257.19	0.96815		4937
Synonymous	-1.34	358	327	1.09	0.0000186	4762
Loss of Function	1.82	64	81.8	0.783	0.00000478	1455

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00084	0.00071	rare
Latino/Admixed American	0.00060	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0020	0.0020	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0011	0.0011	notable
South Asian	0.0019	0.0019	notable
Other	0.00067	0.00066	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates cellular binding of particles and immune complexes that have activated complement.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.764

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium