PCDHA5Protocadherin alpha 5
Autism Reports / Total Reports
5 / 7Rare Variants / Common Variants
6 / 5Aliases
PCDHA5, CNR6, CNRN6, CNRS6, CRNR6, PCDH-ALPHA5Associated Syndromes
-Chromosome Band
5q31.3Associated Disorders
-Relevance to Autism
Five SNPs within PCDHA5 (rs251379, rs1119032, rs17119271, rs155806, and rs17119346) showed significant association with autism in a family-based association study using 14 SNPs within the PCDHA gene cluster in 841 ASD families (574 of which were multiplex) obtained from the Autism Genetic Resource Exchange (AGRE) (Anitha et al., 2012). A rare de novo missense variant in this gene was observed in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; however, this variant was predicted to be benign in Sanders et al., 2015.
Molecular Function
This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain.
External Links
SFARI Genomic Platforms
Reports related to PCDHA5 (7 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Recent Recommendation | Identification of CTCF as a master regulator of the clustered protocadherin genes | Golan-Mashiach M , et al. (2012) | No | - |
2 | Support | De novo gene disruptions in children on the autistic spectrum | Iossifov I , et al. (2012) | Yes | - |
3 | Primary | Protocadherin ? (PCDHA) as a novel susceptibility gene for autism | Anitha A , et al. (2012) | Yes | - |
4 | Support | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
5 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
6 | Support | - | Tuncay IO et al. (2023) | Yes | - |
7 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
Rare Variants (6)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.2063C>T | p.Pro688Leu | missense_variant | De novo | - | - | 37492102 | Tuncay IO et al. (2023) | |
c.2352+60176del | - | intron_variant | De novo | - | Simplex | 22542183 | Iossifov I , et al. (2012) | |
c.2339C>A | p.Thr780Asn | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
c.425_426del | p.Leu142Ter | frameshift_variant | Familial | Maternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
c.1671G>A | p.Glu557= | synonymous_variant | De novo | - | Unknown | 25533962 | Deciphering Developmental Disorders Study (2014) | |
c.855_888del | p.Asp286IlefsTer5 | frameshift_variant | Familial | Paternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) |
Common Variants (5)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.2353-48828T>C | - | intron_variant | - | - | - | 23031252 | Anitha A , et al. (2012) | |
c.2353-76103A>G | - | intron_variant | - | - | - | 23031252 | Anitha A , et al. (2012) | |
c.2500+11686G>A | - | intron_variant | - | - | - | 23031252 | Anitha A , et al. (2012) | |
c.2353-8694A>G | T/C | intron_variant | - | - | - | 23031252 | Anitha A , et al. (2012) | |
c.2352+55210G>A | T/C | intron_variant | - | - | - | 23031252 | Anitha A , et al. (2012) |
SFARI Gene score
Strong Candidate
Five SNPs within PCDHA5 (rs251379, rs1119032, rs17119271, rs155806, and rs17119346) showed significant association with autism in a family-based association study using 14 SNPs within the PCDHA gene cluster in 841 ASD families (574 of which were multiplex) obtained from the Autism Genetic Resource Exchange (AGRE) (Anitha et al., 2012). A rare de novo missense variant in this gene was observed in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; however, this variant was predicted to be benign in Sanders et al., 2015.
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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
Decreased from 3 to 2
Description
Five SNPs within PCDHA5 (rs251379, rs1119032, rs17119271, rs155806, and rs17119346) showed significant association with autism in a family-based association study using 14 SNPs within the PCDHA gene cluster in 841 ASD families (574 of which were multiplex) obtained from the Autism Genetic Resource Exchange (AGRE) (Anitha et al., 2012). A rare de novo missense variant in this gene was observed in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; however, this variant was predicted to be benign in Sanders et al., 2015.
10/1/2019
Decreased from 4 to 3
New Scoring Scheme
Description
Five SNPs within PCDHA5 (rs251379, rs1119032, rs17119271, rs155806, and rs17119346) showed significant association with autism in a family-based association study using 14 SNPs within the PCDHA gene cluster in 841 ASD families (574 of which were multiplex) obtained from the Autism Genetic Resource Exchange (AGRE) (Anitha et al., 2012). A rare de novo missense variant in this gene was observed in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; however, this variant was predicted to be benign in Sanders et al., 2015.
Reports Added
[New Scoring Scheme]7/1/2018
Increased from to 4
Description
Five SNPs within PCDHA5 (rs251379, rs1119032, rs17119271, rs155806, and rs17119346) showed significant association with autism in a family-based association study using 14 SNPs within the PCDHA gene cluster in 841 ASD families (574 of which were multiplex) obtained from the Autism Genetic Resource Exchange (AGRE) (Anitha et al., 2012). A rare de novo missense variant in this gene was observed in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014; however, this variant was predicted to be benign in Sanders et al., 2015.
Krishnan Probability Score
Score 0.49599122450273
Ranking 2720/25841 scored genes
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ExAC Score
Score 0.0035382482028225
Ranking 10862/18225 scored genes
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Sanders TADA Score
Score 0.95035931223291
Ranking 18461/18665 scored genes
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Larsen Cumulative Evidence Score
Score 9
Ranking 206/461 scored genes
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