Human Gene Module / Chromosome 11 / PAX6

PAX6Paired box 6

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
4 / 9
Rare Variants / Common Variants
6 / 0
Aliases
PAX6, AN,  AN2,  D11S812E,  FVH1,  MGDA,  WAGR
Associated Syndromes
WAGR syndrome
Chromosome Band
11p13
Associated Disorders
DD/NDD, ID, ASD
Relevance to Autism

Pax6 heterozygous mutant rats with a spontaneous mutation in the Pax6 gene exhibited abnormalites in social interaction, impairment in rearing activity and in fear-conditioned memory, and abnormal ultrasonic vocalization in female pups (Umeda et al., 2010). Variants affecting PAX6 have been identified in patients presenting with autism, intellectual disability, and additional ocular phenotypes (Davis et al., 2008; Maekawa et al., 2009). PAX6 may be involved in the presentation of developmental delay and autistic behaviors observed in patients with WAGR syndrome caused by 11p14 deletions (Yamamoto et al., 2014).

Molecular Function

This gene encodes a homeobox and paired domain-containing protein that binds DNA and functions as a regulator of transcription. Activity of this protein is key in the development of neural tissues, particularly the eye. Mutations in this gene or in the enhancer regions of this gene can cause ocular disorders such as aniridia (OMIM 106210) and Peter's anomaly.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Rat
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PAX6 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Pax6 3' deletion results in aniridia, autism and mental retardation Davis LK , et al. (2008) Yes ID
2 Support A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient Maekawa M , et al. (2009) Yes ID
3 Primary Evaluation of Pax6 mutant rat as a model for autism Umeda T , et al. (2011) No -
4 Support Pax6-dependent cortical glutamatergic neuronal differentiation regulates autism-like behavior in prenatally valproic acid-exposed rat offspring Kim KC , et al. (2013) No -
5 Support Narrowing of the responsible region for severe developmental delay and autistic behaviors in WAGR syndrome down to 1.6 Mb including PAX6, WT1, and PRRG4 Yamamoto T , et al. (2013) No DD, autistic features
6 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families Trujillano D , et al. (2016) No DD, hypotonia
7 Support Targeted Next-Generation Sequencing of Korean Patients With Developmental Delay and/or Intellectual Disability Han JY , et al. (2019) No ASD
8 Support - Woodbury-Smith M et al. (2022) Yes -
9 Support - Zhou X et al. (2022) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.19G>T p.Gly7Ter stop_gained De novo - - 30631761 Han JY , et al. (2019)
c.-274T>C - missense_variant De novo - Simplex 27848944 Trujillano D , et al. (2016)
c.451G>A p.Ala151Thr missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1473T>C p.Ser491%3D synonymous_variant De novo - - 35205252 Woodbury-Smith M et al. (2022)
- - copy_number_loss Unknown Not paternal Multi-generational 18322702 Davis LK , et al. (2008)
c.136C>G p.Leu46Val missense_variant Familial Paternal Simplex 19607881 Maekawa M , et al. (2009)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Pax6 heterozygous mutant rats with a spontaneous mutation in the Pax6 gene exhibited abnormalites in social interaction, impairment in rearing activity and in fear-conditioned memory, and abnormal ultrasonic vocalization in female pups (PMID 21203536). Variants affecting PAX6 have been identified in patients presenting with autism, intellectual disability, and additional ocular phenotypes (PMIDs 18322702, 19607881). PAX6 may be involved in the presentation of developmental delay and autistic behaviors observed in patients with WAGR syndrome caused by 11p14 deletions (PMID 24357251).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
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."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Pax6 heterozygous mutant rats with a spontaneous mutation in the Pax6 gene exhibited abnormalites in social interaction, impairment in rearing activity and in fear-conditioned memory, and abnormal ultrasonic vocalization in female pups (PMID 21203536). Variants affecting PAX6 have been identified in patients presenting with autism, intellectual disability, and additional ocular phenotypes (PMIDs 18322702, 19607881). PAX6 may be involved in the presentation of developmental delay and autistic behaviors observed in patients with WAGR syndrome caused by 11p14 deletions (PMID 24357251).

Reports Added
[New Scoring Scheme]
1/1/2019
S
icon
S

Score remained at S

Description

Pax6 heterozygous mutant rats with a spontaneous mutation in the Pax6 gene exhibited abnormalites in social interaction, impairment in rearing activity and in fear-conditioned memory, and abnormal ultrasonic vocalization in female pups (PMID 21203536). Variants affecting PAX6 have been identified in patients presenting with autism, intellectual disability, and additional ocular phenotypes (PMIDs 18322702, 19607881). PAX6 may be involved in the presentation of developmental delay and autistic behaviors observed in patients with WAGR syndrome caused by 11p14 deletions (PMID 24357251).

Reports Added
[Targeted Next-Generation Sequencing of Korean Patients With Developmental Delay and/or Intellectual Disability.2019]
10/1/2016
S
icon
S

Score remained at S

Description

Pax6 heterozygous mutant rats with a spontaneous mutation in the Pax6 gene exhibited abnormalites in social interaction, impairment in rearing activity and in fear-conditioned memory, and abnormal ultrasonic vocalization in female pups (PMID 21203536). Variants affecting PAX6 have been identified in patients presenting with autism, intellectual disability, and additional ocular phenotypes (PMIDs 18322702, 19607881). PAX6 may be involved in the presentation of developmental delay and autistic behaviors observed in patients with WAGR syndrome caused by 11p14 deletions (PMID 24357251).

Reports Added
[Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016]
Krishnan Probability Score

Score 0.60412171911307

Ranking 355/25841 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 0.99880789735807

Ranking 1106/18225 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 0.92842310094163

Ranking 10911/18665 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 -0.19459523885631

Ranking 15300/20870 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
2700060E02Rik RIKEN cDNA 2700060E02 gene Mouse Direct Regulation 68045 Q9CQE8
4632404H12Rik RIKEN cDNA 4632404H12 gene Mouse Direct Regulation 74034
8030411F24Rik RIKEN cDNA 8030411F24 gene Mouse Direct Regulation 78609 Q8VII3
A130010J15Rik RIKEN cDNA A130010J15 gene Mouse Direct Regulation 319266 Q9DAE8
Abcc9 ATP-binding cassette, sub-family C (CFTR/MRP), member 9 Mouse Direct Regulation 20928 P70170
Adgrb3 adhesion G protein-coupled receptor B3 Mouse Direct Regulation 210933 Q80ZF8
Arhgdib Rho, GDP dissociation inhibitor (GDI) beta Mouse Direct Regulation 11857 Q61599
Arl14ep ADP-ribosylation factor-like 14 effector protein Mouse Direct Regulation 212772 Q8BIX3
AW549877 expressed sequence AW549877 Mouse Direct Regulation 106064 Q8BR90
AW554918 expressed sequence AW554918 Mouse Direct Regulation 225289 Q6NZK5
Ccdc181 coiled-coil domain containing 181 Mouse Direct Regulation 74895 Q80ZU5
Ccdc186 coiled-coil domain containing 186 Mouse Direct Regulation 213993 Q8C9S4
Cd9 CD9 antigen Mouse Direct Regulation 12527 P40240
Col2a1 collagen, type II, alpha 1 Mouse Direct Regulation 12824 P28481
Enpp2 ectonucleotide pyrophosphatase/phosphodiesterase 2 Mouse Direct Regulation 18606 Q9R1E6
F8a factor 8-associated gene A Mouse Direct Regulation 14070 Q00558
Fam84a family with sequence similarity 84, member A Mouse Direct Regulation 105005 Q9D650
Foxd1 forkhead box D1 Mouse Direct Regulation 15229 Q61345
Gadd45g growth arrest and DNA-damage-inducible 45 gamma Mouse Direct Regulation 23882 Q9Z111
Galnt12 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 12 Mouse Direct Regulation 230145 Q8BGT9
Glis1 GLIS family zinc finger 1 Mouse Direct Regulation 230587 Q8K1M4
Glyctk glycerate kinase Mouse Direct Regulation 235582 Q8QZY2
Gmppb GDP-mannose pyrophosphorylase B Mouse Direct Regulation 331026 Q8BTZ7
Gpr85 G protein-coupled receptor 85 Mouse Direct Regulation 64450 P60894
Harbi1 harbinger transposase derived 1 Mouse Direct Regulation 241547 Q8BR93
Hist2h4 histone cluster 2, H4 Mouse Direct Regulation 97122 P62806
Hmx1 H6 homeobox 1 Mouse Direct Regulation 15371 O70218
Lgalsl lectin, galactoside binding-like Mouse Direct Regulation 216551 Q8VED9
Lix1 limb and CNS expressed 1 Mouse Direct Regulation 66643 Q6P566
Lsm3 LSM3 homolog, U6 small nuclear RNA and mRNA degradation associated Mouse Direct Regulation 67678 P62311
Neurod1 neurogenic differentiation 1 Mouse Direct Regulation 18012 Q60867
Nipsnap3a nipsnap homolog 3A (C. elegans) Mouse Direct Regulation 73398 G3X8S9
Nts neurotensin Mouse Direct Regulation 67405 Q9D3P9
Olfr860 olfactory receptor 860 Mouse Direct Regulation 258521 Q8VFF7
Oser1 oxidative stress responsive serine rich 1 Mouse Direct Regulation 66680 Q9D722
Pacsin3 protein kinase C and casein kinase substrate in neurons 3 Mouse Direct Regulation 80708 Q99JB8
Parn poly(A)-specific ribonuclease (deadenylation nuclease) Mouse Direct Regulation 74108 Q8VDG3
Pcsk1n proprotein convertase subtilisin/kexin type 1 inhibitor Mouse Direct Regulation 30052 Q9QXV0
Pigt phosphatidylinositol glycan anchor biosynthesis, class T Mouse Direct Regulation 78928 Q8BXQ2
Plppr2 phospholipid phosphatase related 2 Mouse Direct Regulation 235044 Q8VCY8
Rab3a Ras-related protein Rab-3A Mouse Direct Regulation 19339 P63011
Rhag Rhesus blood group-associated A glycoprotein Mouse Direct Regulation 19743 Q9QUT0
Rnase12 ribonuclease, RNase A family, 12 (non-active) Mouse Direct Regulation 497106 Q5GAM8
Rnaset2a ribonuclease T2A Mouse Direct Regulation 100037283 Q9CQ01
Sc5d sterol-C5-desaturase Mouse Direct Regulation 235293 O88822
Slc35b3 solute carrier family 35, member B3 Mouse Direct Regulation 108652 Q922Q5
Suclg1 succinate-CoA ligase, GDP-forming, alpha subunit Mouse Direct Regulation 56451 Q9WUM5
Tns2 tensin 2 Mouse Direct Regulation 209039 Q8CGB6
Trf transferrin Mouse Direct Regulation 22041 Q921I1
Ttc36 tetratricopeptide repeat domain 36 Mouse Direct Regulation 192653 Q8VBW8
Zdhhc13 zinc finger, DHHC domain containing 13 Mouse Direct Regulation 243983 Q9CWU2
Zfp281 zinc finger protein 281 Mouse Direct Regulation 226442 Q99LI5
Zfp658 zinc finger protein 658 Mouse Direct Regulation 210104 Q5PPQ4
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