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Relevance to Autism

Rare variants in the PCDH10 gene have been identified with autism in the HMCA cohort (Morrow et al., 2008).

Molecular Function

encodes a cadherin-related neuronal receptor thought to play a role in the estab lishment and function of specific cell-cell connections in the brain.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Identifying autism loci and genes by tracing recent shared ancestry.
ASD
Support
Multiple autism-linked genes mediate synapse elimination via proteasomal degradation of a synaptic scaffold PSD-95.
Support
Integrating de novo and inherited variants in 42
ASD
Support
ASD/OCD-Linked Protocadherin-10 Regulates Synapse
ASD, OCD, MDD
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Support
Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder.
ASD
Support
Genome-wide characteristics of de novo mutations in autism
ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Unknown diagnosis
Highly Cited
Expression of a novel protocadherin, OL-protocadherin, in a subset of functional systems of the developing mouse brain.
Recent Recommendation
Contact-dependent promotion of cell migration by the OL-protocadherin-Nap1 interaction.
Recent Recommendation
OL-Protocadherin is essential for growth of striatal axons and thalamocortical projections.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN189R001a 
 copy_number_loss 
  
  
 Familial 
 Both parents 
 Simplex 
 GEN189R002 
 missense_variant 
 c.1813G>A 
 p.Ala605Thr 
 De novo 
  
 Unknown 
 GEN189R003 
 3_prime_UTR_variant 
 c.*1124T>G 
  
 De novo 
  
 Simplex 
 GEN189R004 
 missense_variant 
 c.2466G>C 
 p.Gln822His 
 De novo 
  
 Simplex 
 GEN189R005 
 synonymous_variant 
 c.1044A>T 
 p.Val348%3D 
 Unknown 
  
  
 GEN189R006 
 frameshift_variant 
 c.2709_2710insTG 
 p.Asp904TrpfsTer3 
 De novo 
  
  
 GEN189R007 
 missense_variant 
 c.1859T>A 
 p.Ile620Asn 
 De novo 
  
  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
4
Duplication
 1
 
4
Duplication
 1
 
4
Deletion
 1
 
4
Duplication
 1
 
4
Duplication
 1
 
4
Duplication
 2
 
4
Deletion
 1
 
4
Deletion-Duplication
 19
 

Model Summary

PCDH10 homozygous knockout mice have defects in telencephalic axon pathways including the inability of thalamocortical and corticothalamic projections to cross the ventral telencephalon, inability of striatal axons to grow out of the ventral telencephalon, the absence of the caudal globus pallidus and the lack of axonal extensions from the striatum.

References

Type
Title
Author, Year
Primary
OL-Protocadherin is essential for growth of striatal axons and thalamocortical projections.
Additional
Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene.

M_PCDH10_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A a lacZ-neo cassette replaced the entire first exon after the initiation site.
Allele Type: Targeted (Reporter)
Strain of Origin: Not Specified
Genetic Background: C57BL/6N
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_PCDH10_2_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Pcdh10 heterozygous knockout mice were generated by replacing the first exon of Pcdh10 with a lacZ-neo selection cassette. Male Pcdh10 heterozygous knockout mice were crossed with female C57BL/6J (B6) mice to generate wild-type or heterozygous null animals.
Allele Type: Targeted (knockout)
Strain of Origin: C57BL/6N
Genetic Background: Mixed, C57BL/6N and C57BL/6J (B6)
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Lexicon Pharmaceuticals, Inc. (Basking Ridge, NJ)

M_PCDH10_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain morphology1
Abnormal
Description: Corticofugal axons halt at the ventral telencephalon
Exp Paradigm: Immunostaining
 Immunohistochemistry
 P2
Brain morphology1
Decreased
Description: Lack of cerebral peduncle and the corticospinal tract
Exp Paradigm: Immunostaining
 Immunohistochemistry
 P2
Size/growth1
Decreased
Description: Decreased body size
Exp Paradigm: General observations
 General observations
 P0
Mortality/lethality1
Increased
Description: Postnatal lethality
Exp Paradigm: General observations
 General observations
 0-3 weeks
Targeted expression1
Decreased
Description: Pcdh10 homozygous knockout mice showed reporter lacz expression in the soma and axons in the striatal neurons indicating disruption of pcdh10 expression.
Exp Paradigm: Lacz staining
 Histology
 E11.517.5
Regulation of gene expression1
Decreased
Description: Missing expression of nkx2.1 in the caudal part of the ventral telencephalon
Exp Paradigm: Gene regulation
 Immunohistochemistry
 E13.5
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_PCDH10_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Female pcdh10 heterozygous knockout mice showed decreased motor coordination in 6 of 10 trials compared to controls. female pcdh10 heterozygous knockout mice showed a slower rate of improvement in motor coordination across the trials relative to controls.
Exp Paradigm: Female only
 Accelerating rotarod test
 4-5 weeks
Neuroreceptor levels: glutamate receptors: ampa receptors1
Decreased
Description: Male pcdh10 heterozygous knockout mice showed decreased nmda receptors glun1 and glun2a in the postsynaptic density fraction of the amygdala, compared to controls
Exp Paradigm: Male only
 Western blot
 Adult
Dendritic architecture: spine morphology1
Abnormal
Description: Male pcdh10 heterozygous knockout mice showed increased filopodia-type immature spines on lateral/basolateral amygdala neurons compared to controls
Exp Paradigm: Male only
 Golgi-cox staining
 Adult
Dendritic architecture: spine density1
Increased
Description: Male pcdh10 heterozygous knockout mice showed increased spine density in the amygdala compared to controls
Exp Paradigm: Male only
 Golgi-cox staining
 Adult
Network excitability1
Decreased
Description: Male pcdh10 heterozygous knockout mice showed reduced connectivity and excitability of the basolateral amygdala compared to controls
Exp Paradigm: Male only, vsdi was used to optically record the transmission of stimulation-evoked activity from la to its functional targets in bla and str in acute ex vivo slices from juvenile mice.
 Voltage sensitive dye imaging (vsdi)
 4-5 weeks
Social approach1
Decreased
Description: Male pcdh10 heterozygous knockout mice showed less increase in the duration of social cylinder sniffing from phase 1 when a stimulus mouse was absent to phase 2 when a stimulus mouse was present, than did male controls
Exp Paradigm: Males only, used social cylinder sniff duration as the primary measure of sociability
 Three-chamber social approach test
 4-5 weeks
Rearing behavior1
Decreased
Description: Male pcdh10 heterozygous knockout mice showed reduced rearing behavior than controls
Exp Paradigm: Male only
 Home cage behavior
 4-5 weeks
Ultrasonic vocalization: isolation induced1
Increased
Description: Pcdh10 heterozygous knockout mice showed increase in ultrasonic vocalizations when separated from their mother, compared to controls
Exp Paradigm: Isolated pups were placed alone in a glass box containing clean bedding
 Monitoring ultrasonic vocalizations
 P6
Anxiety1
 No change
 Elevated zero maze test
 4-5 weeks
Exploratory activity1
 No change
 Three-chamber social approach test
 4-5 weeks
Object recognition memory1
 No change
 Novel object recognition test
 4-5 weeks
General locomotor activity1
 No change
 Three-chamber social approach test
 4-5 weeks
Motor coordination and balance1
 No change
 Accelerating rotarod test
 4-5 weeks
Dendritic architecture: dendritic tree complexity1
 No change
 Golgi-cox staining
 Adult
Dendritic architecture: spine morphology1
 No change
 Golgi-cox staining
 Adult
Neuroreceptor levels: glutamate receptors: ampa receptors1
 No change
 Western blot
 Adult
Synaptic transmission: excitatory1
 No change
 Voltage sensitive dye imaging (vsdi)
 4-5 weeks
Circling1
 No change
 Home cage behavior
 4-5 weeks
Repetitive digging1
 No change
 Home cage behavior
 4-5 weeks
Self grooming: perseveration1
 No change
 Home cage behavior
 4-5 weeks
Olfaction1
 No change
 Olfactory habituation-dishabituation test
 4-5 weeks
Rearing behavior1
 No change
 Home cage behavior
 4-5 weeks
Social approach1
 No change
 Three-chamber social approach test
 4-5 weeks
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Immune response, Maternal behavior, Molecular profile, Physiological parameters, Seizure





Download PCDH10's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
BEX1 brain expressed, X-linked 1 55859 Q9HBH7 qRT-PCR; IP/WB
Ding K , et al. 2008
FCGRT IgG receptor FcRn large subunit p51 2217 P55899 IP; LC-MS/MS
Huttlin EL , et al. 2015
PCDH12 Protocadherin-12 51294 Q9NPG4 IP; LC-MS/MS
Huttlin EL , et al. 2015
PCDHGB1 Protocadherin gamma-B1 56104 Q9Y5G3-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
PCDHGB4 protocadherin gamma subfamily B, 4 8641 Q9UN71 IP; LC-MS/MS
Huttlin EL , et al. 2015
PTGIR Prostacyclin receptor 5739 P43119 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC34A2 Sodium-dependent phosphate transport protein 2B 10568 O95436-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
TMEM30B Cell cycle control protein 50B 161291 Q3MIR4 IP; LC-MS/MS
Huttlin EL , et al. 2015
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011
Nckap1 NCK-associated protein 1 50884 P28660 GST; MS; IP/WB
Nakao S , et al. 2008

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