PCDH18

protein-coding

protocadherin 18, the group of Non-clustered protocadherins

Gene summary

This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This gene encodes a protein which contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. Although its specific function is undetermined, the cadherin-related neuronal receptor is thought to play a role in the establishment and function of specific cell-cell connections in the brain. [provided by RefSeq, Jul 2008]

MANE transcript

NM_019035.5

Inheritance

—

ClinVar variants

U:143B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr4:137,518,918-137,532,494

External References & Databases

Ensembl (ENSG00000189184)

Transcript & Mutation Effects

hg38 • Region Span ~13.6 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 PCDH18 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 142

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019035.5. 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				1 clinvar		1
missense			142 clinvar	2 clinvar		144
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	143	3	0	146

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019035.5	RefSeq	NP_061908.1	4	MANE Select
ENST00000344876.9	Ensembl	ENSP00000355082.4	4	MANE Select
NM_001300828.2	RefSeq	NP_001287757.1	4	Standard
ENST00000412923.6	Ensembl	ENSP00000390688.2	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pcdh18b	Danio rerio	Structure: primary motor neuron Quality: has fewer parts of type abnormal

Gene / Model

Organism

Observed Phenotype

pcdh18b

Danio rerio

Structure: primary motor neuron

Quality: has fewer parts of type

abnormal

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
brain development

Molecular Function

calcium ion binding

Cellular Component

integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000344876
Coding exons: 4
Length: 13577
Individuals with no LoFs: 125664
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125687
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.629	563	607	0.928	0.0000301	7498
Missense (PolyPhen)		192	239.15	0.80284		3007
Synonymous	-0.952	250	232	1.08	0.0000124	2251
Loss of Function	3.90	8	31.7	0.253	0.00000169	416

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

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

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.514
RVIS EVS: -1.26
RVIS percentile EVS: 5.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.287

Gene Damage Prediction

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