CD55

protein-coding

CD55 molecule (Cromer blood group), the group of CD molecules|Sushi domain containing|Complement system regulators and receptors|Blood group antigens

Gene summary

This gene encodes a glycoprotein involved in the regulation of the complement cascade. Binding of the encoded protein to complement proteins accelerates their decay, thereby disrupting the cascade and preventing damage to host cells. Antigens present on this protein constitute the Cromer blood group system (CROM). Alternative splicing results in multiple transcript variants. The predominant transcript variant encodes a membrane-bound protein, but alternatively spliced transcripts may produce soluble proteins. [provided by RefSeq, Jul 2014]

Previous symbols:

MANE transcript

NM_000574.5

Inheritance

AR, BG

ClinVar variants

P:31U:107B:86

Top phenotype

Blood group, Cromer system; Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr1:207,321,519-207,386,804

External References & Databases

Ensembl (ENSG00000196352)

Transcript & Mutation Effects

hg38 • Region Span ~65.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

protein-losing enteropathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009174

Submitter: Labcorp Genetics (formerly Invitae)

protein-losing enteropathySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009174

Submitter: Orphanet

Clinical Genomic Database (CGD)

Blood group, Cromer system; Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathyBG/AR

Manifestation: Hematologic

Intervention: Hematologic

Rationale: For Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, individuals may manifest with features denoted by the condition name, with signs and symptoms including abdominal pain/diarrhea, intestinal lymphangiectasia, hypoproteinemic edema, and malabsorption, as well as recurrent infections; with hypogammaglobulinemia, and angiopathic thromboembolism, and medical management (eg, with terminal complement inhibitor eculizumab) has been described as beneficial on laboratory and clinical parameters; The condition can include recurrent infections, and awareness may allow preventative measures and early and aggressive treatment of infections; Blood group, Cromer system, variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Refs: 7519480; 8837357; 9427725; 21214297; 28657829; 28657861

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CD55 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 242

Inborn genetic diseasesTotal: 44

not specifiedTotal: 35

Complement hyperactivation-angiopathic thrombosis-protein-losing enteropathy syndromeTotal: 15

CD55-related disorderTotal: 12

Cromer blood group systemTotal: 7

CROMER BLOOD GROUP SYSTEM, Dr(a-) PHENOTYPETotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000574.5. 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			1 clinvar	75 clinvar		76
missense	2 clinvar		95 clinvar	9 clinvar	2 clinvar	108
nonsense	6 clinvar	3 clinvar	2 clinvar			11
start loss		2 clinvar	1 clinvar			3
frameshift	8 clinvar		5 clinvar			13
splice donor/acceptor (+/-2bp)	1 clinvar	9 clinvar	3 clinvar			13
Total	17	14	107	84	2	224

Highest pathogenic variant AF is 0.000026349206

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 71 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000574.5	RefSeq	NP_000565.1	10	MANE Select
ENST00000367064.9	Ensembl	ENSP00000356031.4	10	MANE Select
NM_001114752.3	RefSeq	NP_001108224.1	11	Standard
NM_001300902.2	RefSeq	NP_001287831.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Complement and coagulation cascades - Homo sapiens (human)
Viral myocarditis - Homo sapiens (human)
Hematopoietic cell lineage - Homo sapiens (human)
Allograft Rejection
Human Complement System

Biological Process

endoplasmic reticulum to Golgi vesicle-mediated transport
complement activation, classical pathway
positive regulation of cytosolic calcium ion concentration
regulation of complement activation
regulation of lipopolysaccharide-mediated signaling pathway

Molecular Function

virus receptor activity
protein binding
lipid binding

Cellular Component

Golgi membrane
extracellular region
plasma membrane
cell surface
transport vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314754
Coding exons: 11
Length: 39459
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125747
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.923	190	229	0.828	0.0000116	2805
Missense (PolyPhen)		58	86.8	0.66821		1024
Synonymous	0.770	78	87.1	0.895	0.00000451	894
Loss of Function	0.573	19	21.9	0.868	0.00000114	268

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00023	0.00022	rare
South Asian	0.00020	0.00020	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation. Interaction of daf with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade (PubMed:7525274). Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents complement damage (PubMed:28657829). {ECO:0000269|PubMed:7525274, ECO:0000305|PubMed:28657829}.; FUNCTION: (Microbial infection) Acts as a receptor for Human enterovirus 70 and D68 (Probable). {ECO:0000269|PubMed:8764022}.;
Disease: DISEASE: Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) [MIM:226300]: An autosomal recessive disease characterized by abdominal pain and diarrhea, primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease. Patients' T lymphocytes show increased complement activation causing surface deposition of complement and the generation of soluble C5a. {ECO:0000269|PubMed:28657829, ECO:0000269|PubMed:28657861}. Note=The disease is caused by mutations affecting the gene represented in this entry. CHAPLE is caused by biallelic mutations in the CD55 gene.;

Recessive Scores

pRec: 0.364

Intolerance Scores

LoFtool: 0.997
RVIS EVS: 0.35
RVIS percentile EVS: 74.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.823

Gene Damage Prediction

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