Human Gene Module / Chromosome 1 / PATJ

PATJPATJ, crumbs cell polarity complex component

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
9 / 1
Aliases
PATJ, Cipp, INADL,  InaD-like,  hINADL
Associated Syndromes
-
Chromosome Band
1p31.3
Associated Disorders
ASD
Relevance to Autism

Three case-specific loss-of-function variants were identified in the PATJ gene (formerly known as INADL) following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013). Quantitative GWAS analysis of 2,509 ASD probands from a German cohort and the Autism Genome Project in Yousaf et al., 2020 identified an intronic SNP in the PATJ gene (rs2095092) that reached genome-wide significance for association with the Social Interaction subdomain of the Autism Diagnostic Interview-Revised (ADI-R) (P-value 4.3E-08).

Molecular Function

This gene encodes a protein with multiple PDZ domains. PDZ domains mediate protein-protein interactions, and proteins with multiple PDZ domains often organize multimeric complexes at the plasma membrane. This protein localizes to tight junctions and to the apical membrane of epithelial cells. A similar protein in Drosophila is a scaffolding protein which tethers several members of a multimeric signaling complex in photoreceptors.

SFARI Genomic Platforms
Reports related to PATJ (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders Kenny EM , et al. (2013) Yes -
2 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Positive Association Quantitative genome-wide association study of six phenotypic subdomains identifies novel genome-wide significant variants in autism spectrum disorder Yousaf A et al. (2020) Yes ASD sub-phenotype
5 Support - Zhou X et al. (2022) Yes -
6 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
C>T - stop_gained De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.5043+3A>G - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
GC>C - frameshift_variant Unknown - Unknown 24126926 Kenny EM , et al. (2013)
TC>T - frameshift_variant Unknown - Unknown 24126926 Kenny EM , et al. (2013)
c.3838C>T p.Arg1280Ter stop_gained Unknown - Unknown 24126926 Kenny EM , et al. (2013)
c.847C>T p.Arg283Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.3204-1G>A - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.5376_5378+1del - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.4276del p.Ala1426GlnfsTer11 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.3492+2316T>C - intron_variant - - - 32624584 Yousaf A et al. (2020)
SFARI Gene score
2

Strong Candidate

Three case-specific loss-of-function variants were identified in PATJ (formerly known as INADL) following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013); one ASD case was observed with a frameshift variant in unknown origin in this study. A de novo nonsense variant in this gene was identified in an ASD proband from a multiplex family from the Autism Genetic Resource Exchange in Yuen et al., 2017.

Score Delta: Score remained at 2

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

Three case-specific loss-of-function variants were identified in PATJ (formerly known as INADL) following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013); one ASD case was observed with a frameshift variant in unknown origin in this study. A de novo nonsense variant in this gene was identified in an ASD proband from a multiplex family from the Autism Genetic Resource Exchange in Yuen et al., 2017.

7/1/2020
3
icon
3

Decreased from 3 to 3

Description

Three case-specific loss-of-function variants were identified in PATJ (formerly known as INADL) following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013); one ASD case was observed with a frameshift variant in unknown origin in this study. A de novo nonsense variant in this gene was identified in an ASD proband from a multiplex family from the Autism Genetic Resource Exchange in Yuen et al., 2017.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Three case-specific loss-of-function variants were identified in PATJ (formerly known as INADL) following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013); one ASD case was observed with a frameshift variant in unknown origin in this study. A de novo nonsense variant in this gene was identified in an ASD proband from a multiplex family from the Autism Genetic Resource Exchange in Yuen et al., 2017.

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

Decreased from 4 to 4

Description

Three case-specific loss-of-function variants were identified in PATJ (formerly known as INADL) following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013); one ASD case was observed with a frameshift variant in unknown origin in this study. A de novo nonsense variant in this gene was identified in an ASD proband from a multiplex family from the Autism Genetic Resource Exchange in Yuen et al., 2017.

7/1/2018
icon
4

Increased from to 4

Description

Three case-specific loss-of-function variants were identified in PATJ (formerly known as INADL) following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013); one ASD case was observed with a frameshift variant in unknown origin in this study. A de novo nonsense variant in this gene was identified in an ASD proband from a multiplex family from the Autism Genetic Resource Exchange in Yuen et al., 2017.

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