Human Gene Module / Chromosome 13 / CHAMP1

CHAMP1chromosome alignment maintaining phosphoprotein 1

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
2 / 6
Rare Variants / Common Variants
25 / 0
Aliases
CHAMP1, C13orf8,  CAMP,  CHAMP,  MRD40,  ZNF828
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
13q34
Associated Disorders
ASD
Relevance to Autism

Mutations in the CHAMP1 gene are associated with a form of autosomal dominant intellectual disability (MRD40; OMIM 616579); affected individuals frequently display behavioral abnormalities, and autism or autistic features such as stereotypic behavior have been observed in a subset of individuals with this disorder (Hempel et al., 2015; Isidor et al., 2016; Tanaka et al., 2016; Okamoto et al., 2017). A de novo missense variant in the CHAMP1 gene has also been identified in an ASD proband from a multiplex family from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017.

Molecular Function

This gene encodes a zinc finger protein that functions as a regulator of chromosome segregation in mitosis. The encoded protein is required for correct alignment of chromosomes on the metaphase plate, and plays a role in maintaining the attachment of sister kinetochores to microtubules from opposite spindle poles.

Reports related to CHAMP1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De Novo Mutations in CHAMP1 Cause Intellectual Disability with Severe Speech Impairment. Hempel M , et al. (2015) No ASD, stereotypy
2 Support De Novo Truncating Mutations in the Kinetochore-Microtubules Attachment Gene CHAMP1 Cause Syndromic Intellectual Disability. Isidor B , et al. (2016) No ASD
3 Support De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features. Tanaka AJ , et al. (2016) No Autistic features (ritualized behavior)
4 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
5 Support Disturbed chromosome segregation and multipolar spindle formation in a patient with CHAMP1 mutation. Okamoto N , et al. (2017) No Stereotypy
6 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
Rare Variants   (25)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1192C>T p.Arg398Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.1192C>T p.Arg398Ter stop_gained De novo NA - 33004838 Wang T et al. (2020)
c.37C>T p.Arg13Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2438G>T p.Ter813LeuextTer1 stop_lost Unknown - - 33004838 Wang T et al. (2020)
c.1192C>T p.Arg398Ter stop_gained De novo NA - 26340335 Hempel M , et al. (2015)
c.1768C>T p.Gln590Ter stop_gained De novo NA - 26340335 Hempel M , et al. (2015)
c.1945C>T p.Gln649Ter stop_gained De novo NA - 27148580 Tanaka AJ , et al. (2016)
c.1969C>T p.Gln657Ter stop_gained De novo NA - 27148580 Tanaka AJ , et al. (2016)
c.2029G>T p.Glu677Ter stop_gained De novo NA - 27148580 Tanaka AJ , et al. (2016)
c.1002G>A p.Trp334Ter stop_gained De novo NA Simplex 26751395 Isidor B , et al. (2016)
c.1043G>A p.Trp348Ter stop_gained De novo NA Simplex 26751395 Isidor B , et al. (2016)
c.1489C>T p.Arg497Ter stop_gained De novo NA Simplex 26751395 Isidor B , et al. (2016)
c.1880C>G p.Ser627Ter stop_gained De novo NA Simplex 26751395 Isidor B , et al. (2016)
c.606del p.Pro203LeufsTer16 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.606dup p.Pro203SerfsTer14 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1880dup p.Asp628ArgfsTer3 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1044del p.Trp348Ter frameshift_variant De novo NA - 27148580 Tanaka AJ , et al. (2016)
c.635del p.Pro212LeufsTer7 frameshift_variant De novo NA - 26340335 Hempel M , et al. (2015)
c.2067_2070del p.Glu690LeufsTer12 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1292G>A p.Arg431His missense_variant De novo NA Multiplex 28263302 C Yuen RK et al. (2017)
c.958_959del p.Pro320Ter frameshift_variant De novo NA Simplex 26751395 Isidor B , et al. (2016)
c.542_543del p.Ser181CysfsTer5 frameshift_variant De novo NA - 27148580 Tanaka AJ , et al. (2016)
c.1866_1867del p.Asp622GlufsTer8 frameshift_variant De novo NA - 26340335 Hempel M , et al. (2015)
c.1876_1877del p.Ser626LeufsTer4 frameshift_variant De novo NA Simplex 26751395 Isidor B , et al. (2016)
c.2068_2069del p.Glu690SerfsTer5 frameshift_variant De novo NA Simplex 28944241 Okamoto N , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Mutations in the CHAMP1 gene are associated with a form of autosomal dominant intellectual disability (MRD40; OMIM 616579); affected individuals frequently display behavioral abnormalities, and autism or autistic features such as stereotypic behavior have been observed in a subset of individuals with this disorder (Hempel et al., 2015; Isidor et al., 2016; Tanaka et al., 2016; Okamoto et al., 2017). A de novo missense variant in the CHAMP1 gene has also been identified in an ASD proband from a multiplex family from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017.

Score Delta: Score remained at S

1

High Confidence

See all Category 1 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.

10/1/2020
S
icon
S

Score remained at S

Description

Mutations in the CHAMP1 gene are associated with a form of autosomal dominant intellectual disability (MRD40; OMIM 616579); affected individuals frequently display behavioral abnormalities, and autism or autistic features such as stereotypic behavior have been observed in a subset of individuals with this disorder (Hempel et al., 2015; Isidor et al., 2016; Tanaka et al., 2016; Okamoto et al., 2017). A de novo missense variant in the CHAMP1 gene has also been identified in an ASD proband from a multiplex family from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017.

10/1/2019
icon
1

Increased from to 1

New Scoring Scheme
Description

Mutations in the CHAMP1 gene are associated with a form of autosomal dominant intellectual disability (MRD40; OMIM 616579); affected individuals frequently display behavioral abnormalities, and autism or autistic features such as stereotypic behavior have been observed in a subset of individuals with this disorder (Hempel et al., 2015; Isidor et al., 2016; Tanaka et al., 2016; Okamoto et al., 2017). A de novo missense variant in the CHAMP1 gene has also been identified in an ASD proband from a multiplex family from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017.

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.41858382924169

Ranking 21206/25841 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.
ExAC Score

Score 0.98519395105928

Ranking 1978/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.93501702410734

Ranking 12746/18665 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).
Zhang D Score

Score 0.53481755117936

Ranking 309/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
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