Human Gene Module / Chromosome 6 / C4B

C4Bcomplement component 4B

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
1 / 1
Aliases
C4B, CH,  C4A,  C4F,  CO4,  C4B1,  C4B2,  C4B3,  C4B5,  C4A13,  C4A91,  C4B12,  CPAMD3
Associated Syndromes
-
Chromosome Band
6p21.33
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the C4B gene and autism (Odell et al., 2005). As well, studies have found decreased plasma concentrations of the C4B protein in autistic patients.

Molecular Function

The encoded protein is part of the classical pathway of the complement system.

SFARI Genomic Platforms
Reports related to C4B (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Confirmation of the association of the C4B null allelle in autism Odell D , et al. (2005) Yes -
2 Support Both rare and common genetic variants contribute to autism in the Faroe Islands Leblond CS , et al. (2019) Yes -
3 Highly Cited Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility Fielder AH , et al. (1983) No -
4 Highly Cited Diversity of sites for measles virus binding and for inactivation of complement C3b and C4b on membrane cofactor protein CD46 Iwata K , et al. (1995) No -
5 Positive Association DR-positive T cells in autism: association with decreased plasma levels of the complement C4B protein Warren RP , et al. (1995) Yes -
6 Positive Association Decreased plasma concentrations of the C4B complement protein in autism Warren RP , et al. (1994) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3687C>A p.Tyr1229Ter stop_gained Unknown Not paternal Simplex 30675382 Leblond CS , et al. (2019)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
N/A N/A allele - - - 15694999 Odell D , et al. (2005)
SFARI Gene score
2

Strong Candidate

Nominal association in very small samples in a region of extended LD.

Score Delta: Score remained at 2

2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
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2

Decreased from 3 to 2

Description

Nominal association in very small samples in a region of extended LD.

10/1/2019
4
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3

Decreased from 4 to 3

New Scoring Scheme
Description

Nominal association in very small samples in a region of extended LD.

Reports Added
[New Scoring Scheme]
1/1/2019
4
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4

Decreased from 4 to 4

Description

Nominal association in very small samples in a region of extended LD.

7/1/2014
No data
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4

Increased from No data to 4

Description

Nominal association in very small samples in a region of extended LD.

4/1/2014
No data
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4

Increased from No data to 4

Description

Nominal association in very small samples in a region of extended LD.

Krishnan Probability Score

Score 0.43617950692486

Ranking 20366/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Sanders TADA Score

Score 0.94833360866604

Ranking 17641/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Larsen Cumulative Evidence Score

Score 5

Ranking 275/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
C2 Complement C2 Human Protein Binding 717 P06681
C4BPA C4b-binding protein alpha chain Human Protein Binding 722 P04003
C5 Complement C3 Human Protein Binding 718 P01024
CD46 CD46 molecule, complement regulatory protein Human Protein Binding 4179 P15529
CFB complement factor B Human Protein Binding 629 P00751
CR1 Complement receptor type 1 Human Protein Binding 1378 P17927
MASP1 mannan-binding lectin serine peptidase 1 (C4/C2 activating component of Ra-reactive factor) Human Protein Modification 5648 P48740
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