Human Gene Module / Chromosome 7 / CEP41

CEP41testis specific, 14

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 6
Rare Variants / Common Variants
12 / 0
Aliases
CEP41, Cep41,  DKFZp762H1311,  TSGA14
Associated Syndromes
Joubert syndrome 15
Chromosome Band
7q32.2
Associated Disorders
-
Relevance to Autism

Rare mutations in the CEP41 gene have been identified with autism (Korvatska et al., 2011).

Molecular Function

A centrosomal protein

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CEP41 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Imprinting analysis of 10 genes and/or transcripts in a 1.5-Mb MEST-flanking region at human chromosome 7q32 Yamada T , et al. (2004) No -
2 Recent Recommendation Xenopus meiotic microtubule-associated interactome Gache V , et al. (2010) No -
3 Primary Mutations in the TSGA14 gene in families with autism spectrum disorders Korvatska O , et al. (2011) Yes -
4 Support CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium Lee JE , et al. (2012) No -
5 Recent Recommendation Family-based exome sequencing and case-control analysis implicate CEP41 as an ASD gene Patowary A , et al. (2019) Yes -
6 Support - Zhou X et al. (2022) Yes -
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.493G>T p.Asp165Tyr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.107T>C p.Met36Thr missense_variant Unknown - - 30664616 Patowary A , et al. (2019)
c.253G>C p.Ala85Pro missense_variant Unknown - - 30664616 Patowary A , et al. (2019)
c.602C>G p.Ser201Cys missense_variant Unknown - - 30664616 Patowary A , et al. (2019)
c.610A>G p.Met204Val missense_variant Unknown - - 30664616 Patowary A , et al. (2019)
c.616C>G p.Pro206Ala missense_variant Unknown - - 30664616 Patowary A , et al. (2019)
c.725G>A p.Arg242His missense_variant Unknown - - 30664616 Patowary A , et al. (2019)
c.772G>C p.Ala258Pro missense_variant Unknown - - 30664616 Patowary A , et al. (2019)
c.664C>G p.Pro206Ala missense_variant Familial Maternal Multiplex 21438139 Korvatska O , et al. (2011)
c.664C>G p.Pro206Ala missense_variant Familial Paternal Multiplex 21438139 Korvatska O , et al. (2011)
c.766T>G p.Cys240Gly missense_variant Familial Paternal Multiplex 21438139 Korvatska O , et al. (2011)
c.192+5G>A p.Arg33Asp splice_site_variant Familial Paternal Multiplex 21438139 Korvatska O , et al. (2011)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Candidate gene sequencing within a linkage region on 7q32 in an ASD discovery cohort in Korvartska et al., 2011 identified three rare inherited variants in the CEP41 gene: two missense variants that changed conserved residues in the same protein domain, and a splicing variant that resulted in a protein with an internal deletion of 16 residues and a p.Gly33Asp substitution. Statistical analysis demonstrated that these rare CEP41 variants were enriched in affected subjects (6/348 patients versus 2/670 controls, Fisher's exact two tailed P = 0.022). MIP sequencing and subsequent gene-based variant burden analysis of 1004 unrelated familial ASD cases and 1127 controls in Patowary et al., 2019 identified a statistically significant association of CEP41 with ASD with 18 rare missense variants in cases compared to two in controls (P = 6.185E-05, odds ratio 10.26). Moreover, functional analyses of these ASD-associated CEP41 missense variants in zebrafish demonstrated deleterious effects on axonal development, cranial neural crest cell migration, and social behavior. Homozygous variants in the CEP41 gene are responsible for a form of Joubert syndrome (Joubert syndrome 15; OMIM 614464) (Lee et al., 2012); however, while developmental delay and intellectual disability have been observed in individuals with this syndrome, to date autism or autistic features have not.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
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.

10/1/2019
2
icon
2

Score remained at 2

New Scoring Scheme
Description

Candidate gene sequencing within a linkage region on 7q32 in an ASD discovery cohort in Korvartska et al., 2011 identified three rare inherited variants in the CEP41 gene: two missense variants that changed conserved residues in the same protein domain, and a splicing variant that resulted in a protein with an internal deletion of 16 residues and a p.Gly33Asp substitution. Statistical analysis demonstrated that these rare CEP41 variants were enriched in affected subjects (6/348 patients versus 2/670 controls, Fisher's exact two tailed P = 0.022). MIP sequencing and subsequent gene-based variant burden analysis of 1004 unrelated familial ASD cases and 1127 controls in Patowary et al., 2019 identified a statistically significant association of CEP41 with ASD with 18 rare missense variants in cases compared to two in controls (P = 6.185E-05, odds ratio 10.26). Moreover, functional analyses of these ASD-associated CEP41 missense variants in zebrafish demonstrated deleterious effects on axonal development, cranial neural crest cell migration, and social behavior. Homozygous variants in the CEP41 gene are responsible for a form of Joubert syndrome (Joubert syndrome 15; OMIM 614464) (Lee et al., 2012); however, while developmental delay and intellectual disability have been observed in individuals with this syndrome, to date autism or autistic features have not.

Reports Added
[New Scoring Scheme]
1/1/2019
3
icon
2

Decreased from 3 to 2

Description

Candidate gene sequencing within a linkage region on 7q32 in an ASD discovery cohort in Korvartska et al., 2011 identified three rare inherited variants in the CEP41 gene: two missense variants that changed conserved residues in the same protein domain, and a splicing variant that resulted in a protein with an internal deletion of 16 residues and a p.Gly33Asp substitution. Statistical analysis demonstrated that these rare CEP41 variants were enriched in affected subjects (6/348 patients versus 2/670 controls, Fisher's exact two tailed P = 0.022). MIP sequencing and subsequent gene-based variant burden analysis of 1004 unrelated familial ASD cases and 1127 controls in Patowary et al., 2019 identified a statistically significant association of CEP41 with ASD with 18 rare missense variants in cases compared to two in controls (P = 6.185E-05, odds ratio 10.26). Moreover, functional analyses of these ASD-associated CEP41 missense variants in zebrafish demonstrated deleterious effects on axonal development, cranial neural crest cell migration, and social behavior. Homozygous variants in the CEP41 gene are responsible for a form of Joubert syndrome (Joubert syndrome 15; OMIM 614464) (Lee et al., 2012); however, while developmental delay and intellectual disability have been observed in individuals with this syndrome, to date autism or autistic features have not.

Reports Added
[CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium.2012] [Family-based exome sequencing and case-control analysis implicate CEP41 as an ASD gene.2019]
7/1/2014
No data
icon
3

Increased from No data to 3

Description

Rare mutations in this gene are reported to involve Joubert syndrome including MR but not ASD in one family. Candidate sequencing in an ASD discovery cohort in this linkage region was performed by Korvatska et al. (2011). Two missense variants were found that changed conserved residues in the same protein domain. A third variant altered splicing, which resulted in a protein with an internal deletion of 16 residues and a G33D substitution. These rare CEP41 variants are enriched in the affected subjects (6/348 patients versus 2/670 controls, Fisher's exact two tailed P = 0.022).

4/1/2014
No data
icon
3

Increased from No data to 3

Description

Rare mutations in this gene are reported to involve Joubert syndrome including MR but not ASD in one family. Candidate sequencing in an ASD discovery cohort in this linkage region was performed by Korvatska et al. (2011). Two missense variants were found that changed conserved residues in the same protein domain. A third variant altered splicing, which resulted in a protein with an internal deletion of 16 residues and a G33D substitution. These rare CEP41 variants are enriched in the affected subjects (6/348 patients versus 2/670 controls, Fisher's exact two tailed P = 0.022).

Krishnan Probability Score

Score 0.49176334623948

Ranking 5115/25841 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 0.0001256293036554

Ranking 12967/18225 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 0.89974031586924

Ranking 6355/18665 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
Larsen Cumulative Evidence Score

Score 7

Ranking 240/461 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.
Original Source
Zhang D Score

Score -0.2121919257061

Ranking 15687/20870 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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