C8B

complement C8 beta chain, the group of Complement system activation components

Basic information

Region (hg38): 1:56929207-56974383

Links

ENSG00000021852 ∙ NCBI:732 ∙ OMIM:120960 ∙ HGNC:1353 ∙ Uniprot:P07358 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• type II complement component 8 deficiency (Moderate), mode of inheritance: AR
• type II complement component 8 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Complement component 8 deficiency, type II	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	6822660; 8098723; 9476133; 21270745; 22123893

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C8B gene.

• not_provided (360 variants)
• Inborn_genetic_diseases (85 variants)
• Type_II_complement_component_8_deficiency (26 variants)
• C8B-related_disorder (12 variants)
• Complement_component_6_deficiency (2 variants)
• not_specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C8B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000066.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	91	8	101
missense			186	14	2	202
nonsense	14	3	4			21
start loss						0
frameshift	17	1				18
splice donor/acceptor (+/-2bp)		8				8
Total	31	12	192	105	10

Highest pathogenic variant AF is 0.00132238

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C8B	protein_coding	protein_coding	ENST00000371237	12	36931

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.31e-19	0.00372	125315	0	433	125748	0.00172

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.743	351	314	1.12	0.0000176	3895
Missense in Polyphen		110	100.13	1.0985		1296
Synonymous	-2.19	146	116	1.26	0.00000674	1090
Loss of Function	0.109	29	29.6	0.978	0.00000155	364

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00309	0.00309
Ashkenazi Jewish	0.00129	0.00129
East Asian	0.000327	0.000326
Finnish	0.000370	0.000370
European (Non-Finnish)	0.00256	0.00256
Middle Eastern	0.000327	0.000326
South Asian	0.000555	0.000555
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells.
• Disease: DISEASE: Complement component 8 deficiency, 2 (C8D2) [MIM:613789]: A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Prion diseases - Homo sapiens (human);Complement and coagulation cascades - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Allograft Rejection;Complement Activation;alternative complement pathway;classical complement pathway;lectin induced complement pathway;Innate Immune System;Immune System;Regulation of Complement cascade;Terminal pathway of complement;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.431
• rvis_EVS: 0.56
• rvis_percentile_EVS: 81.67

Haploinsufficiency Scores

• pHI: 0.0529
• hipred: N
• hipred_score: 0.187

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.869

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: C8b
• Phenotype: hematopoietic system phenotype

Gene ontology

• Biological process: immune response;complement activation;complement activation, alternative pathway;complement activation, classical pathway;cytolysis;regulation of complement activation
• Cellular component: extracellular region;membrane attack complex;membrane;extracellular exosome;extracellular vesicle
• Molecular function: protein-containing complex binding