CD46

CD46 molecule, the group of CD molecules|Sushi domain containing|Complement system regulators and receptors

Basic information

Region (hg38): 1:207752037-207795513

Previous symbols: [ "MIC10", "MCP" ]

Links

ENSG00000117335 ∙ NCBI:4179 ∙ OMIM:120920 ∙ HGNC:6953 ∙ Uniprot:P15529 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• atypical hemolytic-uremic syndrome with MCP/CD46 anomaly (Definitive), mode of inheritance: Semidominant
• atypical hemolytic-uremic syndrome with MCP/CD46 anomaly (Strong), mode of inheritance: AD
• atypical hemolytic-uremic syndrome with MCP/CD46 anomaly (Strong), mode of inheritance: AD
• atypical hemolytic-uremic syndrome with MCP/CD46 anomaly (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemolytic uremic syndrome, atypical, susceptibility to, 2	AD/AR	Hematologic; Pharmacogenomic; Renal	In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications), though treatment with plasma infusion was not reported to result in improved disease resolution in individuals with MCP variants	Hematologic; Renal	14615110; 14566051; 15661753; 16621965; 16762990; 16386793; 17617869; 16882452; 20595690; 20301541
Digenic inheritance (with CFH) has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD46 gene.

• not provided (12 variants)
• Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD46 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	26	1	30
missense		5	128	2	2	137
nonsense	4	1				5
start loss						0
frameshift	10	3				13
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	8	1			10
splice region			7	9	1	17
non coding		1	35	39	35	110
Total	15	18	168	67	38

Highest pathogenic variant AF is 0.0000131

Variants in CD46

This is a list of pathogenic ClinVar variants found in the CD46 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-207752086-A-G		Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly	Uncertain significance (Jan 12, 2018)
1-207752202-C-A		Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly	Likely benign (Jan 13, 2018)
1-207752203-C-T		Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly	Uncertain significance (Jan 12, 2018)
1-207752207-C-T		Atypical hemolytic-uremic syndrome	Uncertain significance (Jun 14, 2016)
1-207752222-C-T		not specified	Uncertain significance (Aug 24, 2023)
1-207752223-C-T			Uncertain significance (Jan 27, 2022)
1-207752224-C-T			Likely benign (Dec 01, 2023)
1-207752227-C-A		CD46-related disorder	Likely benign (Sep 19, 2023)
1-207752229-G-T			Uncertain significance (May 29, 2022)
1-207752242-C-G			Likely benign (May 05, 2023)
1-207752247-C-T			Uncertain significance (Jun 28, 2022)
1-207752250-C-T		Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly • not specified • CD46-related disorder • Atypical hemolytic-uremic syndrome	Benign (Jan 29, 2024)
1-207752252-T-C			Uncertain significance (May 04, 2021)
1-207752264-G-A			Uncertain significance (Jun 15, 2022)
1-207752269-G-T			Uncertain significance (Sep 07, 2022)
1-207752270-C-T		not specified	Uncertain significance (May 23, 2023)
1-207752271-T-C			Uncertain significance (Sep 01, 2022)
1-207752277-C-A			Uncertain significance (Feb 10, 2022)
1-207752280-C-G		not specified	Uncertain significance (May 03, 2023)
1-207752282-A-C			Uncertain significance (Dec 06, 2023)
1-207752282-A-G		Atypical hemolytic-uremic syndrome	Uncertain significance (Nov 28, 2023)
1-207752283-T-C		not specified	Uncertain significance (May 20, 2023)
1-207752284-G-A		Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly	Uncertain significance (Mar 08, 2023)
1-207752294-CT-C		Atypical hemolytic-uremic syndrome	Likely pathogenic (Mar 01, 2020)
1-207752298-ACTC-A			Uncertain significance (Jan 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD46	protein_coding	protein_coding	ENST00000322875	13	43457

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.70e-7	0.959	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.624	193	219	0.881	0.0000108	2575
Missense in Polyphen		42	53.817	0.78042		668
Synonymous	1.02	63	74.2	0.849	0.00000406	756
Loss of Function	1.96	14	24.4	0.573	0.00000120	307

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00104	0.00103
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000328	0.0000327
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement- mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in the fusion of the spermatozoa with the oocyte during fertilization. Also acts as a costimulatory factor for T- cells which induces the differentiation of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells suppress immune responses by secreting interleukin-10, and therefore are thought to prevent autoimmunity. {ECO:0000269|PubMed:10843656, ECO:0000269|PubMed:12540904}.; FUNCTION: (Microbial infection) Acts as a receptor for Adenovirus subgroup B2 and Ad3. {ECO:0000269|PubMed:12915534, ECO:0000269|PubMed:14566335, ECO:0000269|PubMed:15047806, ECO:0000269|PubMed:15078926, ECO:0000269|PubMed:15919905, ECO:0000269|PubMed:16254377}.; FUNCTION: (Microbial infection) Acts as a receptor for Herpesvirus 6/HHV-6. {ECO:0000269|PubMed:12663806, ECO:0000269|PubMed:12724329}.
• Disease: DISEASE: Hemolytic uremic syndrome atypical 2 (AHUS2) [MIM:612922]: An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. {ECO:0000269|PubMed:14566051, ECO:0000269|PubMed:16386793, ECO:0000269|PubMed:16621965, ECO:0000269|PubMed:20513133}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype. Patients with CD46 mutations seem to have an overall better prognosis compared to patients carrying CFH mutations.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Measles - Homo sapiens (human);Human Complement System;Dengue-2 Interactions with Complement and Coagulation Cascades;Complement and Coagulation Cascades;Innate Immune System;Immune System;Regulation of Complement cascade;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.177

Intolerance Scores

• loftool: 0.983
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.7

Haploinsufficiency Scores

• pHI: 0.105
• hipred: N
• hipred_score: 0.396
• ghis: 0.432

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cd46
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype

Gene ontology

• Biological process: adaptive immune response;T cell mediated immunity;complement activation, classical pathway;single fertilization;regulation of Notch signaling pathway;positive regulation of gene expression;negative regulation of gene expression;regulation of complement activation;interleukin-10 production;positive regulation of interleukin-10 production;sequestering of extracellular ligand from receptor;positive regulation of T cell proliferation;positive regulation of memory T cell differentiation;innate immune response;positive regulation of regulatory T cell differentiation;viral entry into host cell;positive regulation of transforming growth factor beta production
• Cellular component: inner acrosomal membrane;plasma membrane;integral component of plasma membrane;focal adhesion;cell surface;extracellular exosome
• Molecular function: virus receptor activity;protein binding;signaling receptor activity;cadherin binding