Human Gene Module / Chromosome 6 / PEX7

PEX7peroxisomal biogenesis factor 7

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
2 / 2
Aliases
PEX7, RP11-55K22.6,  PTS2R,  RCDP1,  RD
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
6q23.3
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the PEX7 gene and ASD in a Korean population cohort (Ro et al., 2012). A homozygous loss-of-function missense variant in the PEX7 gene was identified in three affected children born to consanguineous parents from a multiplex ASD pedigree; this variant was heterozygous in both parents and in three unaffected children (Yu et al., 2013).

Molecular Function

This gene encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Defects in this gene cause peroxisome biogenesis disorders (PBDs), which are characterized by multiple defects in peroxisome function.

Reports related to PEX7 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Association between peroxisomal biogenesis factor 7 and autism spectrum disorders in a Korean population. Ro M , et al. (2012) Yes -
2 Recent Recommendation Using whole-exome sequencing to identify inherited causes of autism. Yu TW , et al. (2013) Yes -
3 Support Large-scale discovery of novel genetic causes of developmental disorders. Deciphering Developmental Disorders Study (2014) No -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.225G>C p.Trp75Cys missense_variant Familial Both parents Multiplex 23352163 Yu TW , et al. (2013)
c.883A>G p.Ser295Gly missense_variant De novo NA Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.527-3273G>A;c.413-3273G>A;c.340-6536G>A;c.526+17173G>A A/G intron_variant - - - 22378669 Ro M , et al. (2012)
c.804-11976G>A;c.690-11976G>A;c.510-11976G>A;c.527-11976G>A A/G intron_variant - - - 22378669 Ro M , et al. (2012)
SFARI Gene score
3

Suggestive Evidence

Genetic association has been found between the PEX7 gene and ASD in a Korean population cohort (Ro et al., 2012). A homozygous loss-of-function missense variant in the PEX7 gene was identified in three affected children born to consanguineous parents from a multiplex ASD pedigree; this variant was heterozygous in both parents and in three unaffected children (Yu et al., 2013).

Score Delta: Score remained at 4

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Genetic association has been found between the PEX7 gene and ASD in a Korean population cohort (Ro et al., 2012). A homozygous loss-of-function missense variant in the PEX7 gene was identified in three affected children born to consanguineous parents from a multiplex ASD pedigree; this variant was heterozygous in both parents and in three unaffected children (Yu et al., 2013).

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

Genetic association has been found between the PEX7 gene and ASD in a Korean population cohort (Ro et al., 2012). A homozygous loss-of-function missense variant in the PEX7 gene was identified in three affected children born to consanguineous parents from a multiplex ASD pedigree; this variant was heterozygous in both parents and in three unaffected children (Yu et al., 2013).

Krishnan Probability Score

Score 0.32798561109488

Ranking 25180/25841 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 6.8612830746604E-8

Ranking 15772/18225 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 0.81563175502084

Ranking 2510/18665 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 16

Ranking 123/461 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.
Zhang D Score

Score -0.033856057012926

Ranking 9825/20870 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.
Submit New Gene

Report an Error

SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
Close