Human Gene Module / Chromosome 13 / CHAMP1

CHAMP1chromosome alignment maintaining phosphoprotein 1

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
3 / 18
Rare Variants / Common Variants
43 / 0
Aliases
CHAMP1, C13orf8,  CAMP,  CHAMP,  MRD40,  ZNF828
Associated Syndromes
-
Chromosome Band
13q34
Associated Disorders
ASD, EPS
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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CHAMP1 (18 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 -
7 Recent Recommendation - Garrity M et al. (2021) No ASD, epilepsy/seizures
8 Support - Dong Y et al. (2021) No DD
9 Support - Asakura Y et al. (2021) No DD, ID
10 Support - Pode-Shakked B et al. (2021) No -
11 Support - Levy T et al. (2022) No ASD, ADHD
12 Support - Zhou X et al. (2022) Yes -
13 Support - Nagai M et al. (2022) No -
14 Support - Amenta S et al. (2023) No Stereotypy
15 Support - Levy T et al. (2023) No -
16 Support - Abi Raad S et al. (2023) No Stereotypy
17 Support - M Cecilia Poli et al. () No -
18 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (43)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - Simplex 36797464 Amenta S et al. (2023)
c.1192C>T p.Arg398Ter stop_gained De novo - - 33004838 Wang T et al. (2020)
c.1192C>T p.Arg398Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.37C>T p.Arg13Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1192C>T p.Arg398Ter stop_gained De novo - - 26340335 Hempel M , et al. (2015)
c.1768C>T p.Gln590Ter stop_gained De novo - - 26340335 Hempel M , et al. (2015)
c.1489C>T p.Arg497Ter stop_gained De novo - - 34021018 Garrity M et al. (2021)
c.1544G>A p.Trp515Ter stop_gained De novo - - 34021018 Garrity M et al. (2021)
c.1657G>T p.Glu553Ter stop_gained De novo - - 34021018 Garrity M et al. (2021)
c.2127T>G p.Tyr709Ter stop_gained De novo - - 34021018 Garrity M et al. (2021)
c.1945C>T p.Gln649Ter stop_gained De novo - - 27148580 Tanaka AJ , et al. (2016)
c.1969C>T p.Gln657Ter stop_gained De novo - - 27148580 Tanaka AJ , et al. (2016)
c.2029G>T p.Glu677Ter stop_gained De novo - - 27148580 Tanaka AJ , et al. (2016)
c.2438G>T p.Ter813LeuextTer1 stop_lost Unknown - - 33004838 Wang T et al. (2020)
c.1489C>T p.Arg497Ter stop_gained De novo - - 39039281 Axel Schmidt et al. (2024)
c.1858A>T p.Lys620Ter stop_gained De novo - Simplex 36797464 Amenta S et al. (2023)
c.959dup p.Arg321Ter frameshift_variant De novo - - 34021018 Garrity M et al. (2021)
c.1002G>A p.Trp334Ter stop_gained De novo - Simplex 26751395 Isidor B , et al. (2016)
c.1043G>A p.Trp348Ter stop_gained De novo - Simplex 26751395 Isidor B , et al. (2016)
c.1489C>T p.Arg497Ter stop_gained De novo - Simplex 26751395 Isidor B , et al. (2016)
c.1880C>G p.Ser627Ter stop_gained De novo - Simplex 26751395 Isidor B , et al. (2016)
c.1465C>T p.Gln489Ter stop_gained De novo - Simplex 34404773 Asakura Y et al. (2021)
c.67G>A p.Gly23Ser missense_variant De novo - Simplex 36797464 Amenta S et al. (2023)
c.1044del p.Trp348Ter frameshift_variant De novo - - 27148580 Tanaka AJ , et al. (2016)
c.1192C>T p.Arg398Ter stop_gained De novo - Simplex 37628598 Abi Raad S et al. (2023)
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.1596C>T p.Pro532%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.635del p.Pro212LeufsTer7 frameshift_variant De novo - - 26340335 Hempel M , et al. (2015)
c.661dup p.Thr221AsnfsTer3 frameshift_variant De novo - - 34021018 Garrity M et al. (2021)
c.1850dup p.Lys618GlufsTer13 frameshift_variant De novo - - 34021018 Garrity M et al. (2021)
c.1292G>A p.Arg431His missense_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.2067_2070del p.Glu690LeufsTer12 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.542_543del p.Ser181CysfsTer5 frameshift_variant De novo - - 34021018 Garrity M et al. (2021)
c.958_959del p.Pro320Ter frameshift_variant De novo - Simplex 26751395 Isidor B , et al. (2016)
c.542_543del p.Ser181CysfsTer5 frameshift_variant De novo - - 27148580 Tanaka AJ , et al. (2016)
c.1866_1867del p.Asp622GlufsTer8 frameshift_variant De novo - - 26340335 Hempel M , et al. (2015)
c.1903_1906del p.Glu635ThrfsTer2 frameshift_variant De novo - - 38177409 M Cecilia Poli et al. ()
c.1995dup p.Ser666Ter frameshift_variant De novo - Simplex 34580403 Pode-Shakked B et al. (2021)
c.530delinsTTT p.Ser177PhefsTer2 frameshift_variant De novo - Simplex 34257719 Dong Y et al. (2021)
c.1876_1877del p.Ser626LeufsTer4 frameshift_variant De novo - Simplex 26751395 Isidor B , et al. (2016)
c.2068_2069del p.Glu690SerfsTer5 frameshift_variant De novo - Simplex 28944241 Okamoto N , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met
See SFARI Gene'scoring criteria
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.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2021
1
icon
1

Score remained at 1

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
[Neurodevelopmental Phenotypes in Individuals with Pathogenic Variants in CHAMP12021]
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.
Original Source
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
Original Source
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).
Original Source
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.
Original Source
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