Human Gene Module / Chromosome 2 / PXDN

PXDNperoxidasin

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 8
Rare Variants / Common Variants
12 / 0
Aliases
PXDN, ASGD7,  COPOA,  D2S448,  D2S448E,  MG50,  PRG2,  PXN,  VPO
Associated Syndromes
-
Chromosome Band
2p25.3
Associated Disorders
-
Relevance to Autism

A germline mosiac duplication of the PXDN and MYT1L genes was transmitted from a psychiatrically normal mother to two male half-siblings with autism (Meyer et al., 2012).

Molecular Function

This gene encodes a heme-containing peroxidase that is secreted into the extracellular matrix and is involved in extracellular matrix formation. Homozygous mutations in PXDN have been reported in two consanguineous Pakistani families with congenital cataract-microcornea with mild to moderate corneal opacity and in a consanguineous Cambodian family with developmental glaucoma and severe corneal opacification (Khan et al., 2011).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PXDN (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Germline mosaic transmission of a novel duplication of PXDN and MYT1L to two male half-siblings with autism Meyer KJ , et al. (2011) Yes -
2 Support Identification of rare copy number variants in high burden schizophrenia families Van Den Bossche MJ , et al. (2013) No -
3 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
4 Support Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
5 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
6 Support - Kritioti E et al. (2021) No -
7 Support - Woodbury-Smith M et al. (2022) Yes -
8 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.3202G>A p.Ala1068Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_gain Familial Maternal Multiplex 22157634 Meyer KJ , et al. (2011)
c.376G>T p.Asp126Tyr missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.2021G>T p.Arg674Leu missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.2335C>T p.Arg779Trp missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.1955G>C p.Arg652Pro missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1928G>A p.Arg643Gln missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3906C>G p.Asp1302Glu missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
- - copy_number_gain Familial Paternal Multiplex 23505263 Van Den Bossche MJ , et al. (2013)
c.2098G>T p.Gly700Ter stop_gained Familial Both parents - 34324503 Kritioti E et al. (2021)
c.1681-2A>C - splice_site_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.3416_3424del p.Leu1139_Glu1141del inframe_deletion De novo - Simplex 35982159 Zhou X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Duplications affecting the PXDN gene have been identified in individuals with ASD (Meyer et al., 2012) and schizophrenia (Van Den Bossche et al., 2013); however, as such duplications also affect the high confidence ASD candidate gene MYT1L, it is difficult to assess the genetic contribution of PXDN to ASD based solely as this evidence. A de novo missense variant that was predicted to be probably damaging was identified in the PXDN gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, and rare inherited missense variants predicted to be damaging by multiple in silico algorithms were observed in Chinese ASD probands in Li et al., 2017.

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Duplications affecting the PXDN gene have been identified in individuals with ASD (Meyer et al., 2012) and schizophrenia (Van Den Bossche et al., 2013); however, as such duplications also affect the high confidence ASD candidate gene MYT1L, it is difficult to assess the genetic contribution of PXDN to ASD based solely as this evidence. A de novo missense variant that was predicted to be probably damaging was identified in the PXDN gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, and rare inherited missense variants predicted to be damaging by multiple in silico algorithms were observed in Chinese ASD probands in Li et al., 2017.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Duplications affecting the PXDN gene have been identified in individuals with ASD (Meyer et al., 2012) and schizophrenia (Van Den Bossche et al., 2013); however, as such duplications also affect the high confidence ASD candidate gene MYT1L, it is difficult to assess the genetic contribution of PXDN to ASD based solely as this evidence. A de novo missense variant that was predicted to be probably damaging was identified in the PXDN gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, and rare inherited missense variants predicted to be damaging by multiple in silico algorithms were observed in Chinese ASD probands in Li et al., 2017.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

Duplications affecting the PXDN gene have been identified in individuals with ASD (Meyer et al., 2012) and schizophrenia (Van Den Bossche et al., 2013); however, as such duplications also affect the high confidence ASD candidate gene MYT1L, it is difficult to assess the genetic contribution of PXDN to ASD based solely as this evidence. A de novo missense variant that was predicted to be probably damaging was identified in the PXDN gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, and rare inherited missense variants predicted to be damaging by multiple in silico algorithms were observed in Chinese ASD probands in Li et al., 2017.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2018
icon
4

Increased from to 4

Description

Duplications affecting the PXDN gene have been identified in individuals with ASD (Meyer et al., 2012) and schizophrenia (Van Den Bossche et al., 2013); however, as such duplications also affect the high confidence ASD candidate gene MYT1L, it is difficult to assess the genetic contribution of PXDN to ASD based solely as this evidence. A de novo missense variant that was predicted to be probably damaging was identified in the PXDN gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, and rare inherited missense variants predicted to be damaging by multiple in silico algorithms were observed in Chinese ASD probands in Li et al., 2017.

Krishnan Probability Score

Score 0.44409109046729

Ranking 16224/25841 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 2.0360283006253E-5

Ranking 13874/18225 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 0.94073251282992

Ranking 14674/18665 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 0.32859620650399

Ranking 2308/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ADCYAP1 Pituitary adenylate cyclase-activating polypeptide Human Protein Binding 116 P18509
INSL5 Insulin-like peptide INSL5 Human Protein Binding 10022 Q9Y5Q6
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