PCDHGC3

protein-coding

protocadherin gamma subfamily C, 3, the group of Clustered protocadherins

Gene summary

This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

Previous symbols:

PCDH2

MANE transcript

NM_002588.4

Inheritance

—

ClinVar variants

U:109B:9

Top phenotype

Inborn genetic diseases

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr5:141,475,947-141,512,977

External References & Databases

Ensembl (ENSG00000240184)

Transcript & Mutation Effects

hg38 • Region Span ~37.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PCDHGC3 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 217

Inborn genetic diseasesTotal: 104

not providedTotal: 26

Neurodevelopmental disorder with poor growth and skeletal anomaliesTotal: 11

PCDHGC4-related disorderTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002588.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar	3 clinvar	7
missense			109 clinvar	2 clinvar		111
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	109	6	3	118

Highest pathogenic variant AF is 0.0000043382875

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002588.4	RefSeq	NP_002579.2	4	MANE Select
ENST00000308177.5	Ensembl	ENSP00000312070.3	4	MANE Select
NM_032402.2	RefSeq	NP_115778.1	1	Standard
NM_032403.3	RefSeq	NP_115779.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell adhesion
homophilic cell adhesion via plasma membrane adhesion molecules
calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules
synapse organization

Molecular Function

calcium ion binding

Cellular Component

integral component of plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000308177
Coding exons: 4
Length: 36963
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.41	472	567	0.833	0.0000330	6015
Missense (PolyPhen)		151	214.97	0.70243		2341
Synonymous	0.857	233	250	0.931	0.0000159	2073
Loss of Function	3.59	7	27.2	0.257	0.00000149	292

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000079	0.000079	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.443
RVIS EVS: -1.55
RVIS percentile EVS: 3.25

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0980

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium