PCDH9

protein-coding

protocadherin 9, the group of Non-clustered protocadherins

Gene summary

This gene encodes a member of the protocadherin family, and cadherin superfamily, of transmembrane proteins containing cadherin domains. These proteins mediate cell adhesion in neural tissues in the presence of calcium. The encoded protein may be involved in signaling at neuronal synaptic junctions. Sharing a characteristic with other protocadherin genes, this gene has a notably large exon that encodes multiple cadherin domains and a transmembrane region. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

MANE transcript

NM_203487.3

Inheritance

—

ClinVar variants

U:132B:9

Top phenotype

PCDH9-related disorder

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr13:66,302,834-67,230,445

External References & Databases

Ensembl (ENSG00000184226)

Transcript & Mutation Effects

hg38 • Region Span ~927.6 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 PCDH9 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 124

PCDH9-related disorderTotal: 7

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_203487.3. 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			2 clinvar	3 clinvar	1 clinvar	6
missense			130 clinvar	5 clinvar		135
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	132	8	1	141

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_203487.3	RefSeq	NP_982354.1	4	MANE Select
ENST00000377865.7	Ensembl	ENSP00000367096.2	4	MANE Select
NM_001318372.2	RefSeq	NP_001305301.1	4	Standard
NM_001318373.2	RefSeq	NP_001305302.1	3	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

Molecular Function

calcium ion binding

Cellular Component

integral component of plasma membrane
growth cone
cell-cell contact zone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000544246
Coding exons: 4
Length: 927502
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125747
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.33	495	664	0.746	0.0000349	8202
Missense (PolyPhen)		143	276.07	0.51799		3636
Synonymous	-0.335	264	257	1.03	0.0000145	2478
Loss of Function	4.25	6	31.9	0.188	0.00000178	425

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Potential calcium-dependent cell-adhesion protein.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.212
RVIS EVS: -0.13
RVIS percentile EVS: 44.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.906

Gene Damage Prediction

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