CDH18

protein-coding

cadherin 18, the group of Type II classical cadherins

Gene summary

This gene encodes a type II classical cadherin from the cadherin superfamily of integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is expressed specifically in the central nervous system and is putatively involved in synaptic adhesion, axon outgrowth and guidance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

MANE transcript

NM_004934.5

Inheritance

—

ClinVar variants

U:106B:11

Top phenotype

CDH18-related disorder

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr5:19,471,296-20,575,873

External References & Databases

Ensembl (ENSG00000145526)

Transcript & Mutation Effects

hg38 • Region Span ~1,104.6 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 CDH18 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 108

CDH18-related disorderTotal: 3

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004934.5. 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	6 clinvar	2 clinvar	9
missense			103 clinvar	3 clinvar		106
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	106	9	2	117

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004934.5	RefSeq	NP_004925.1	11	MANE Select
ENST00000382275.6	Ensembl	ENSP00000371710.1	11	MANE Select
NM_001167667.3	RefSeq	NP_001161139.1	10	Standard
NM_001291956.3	RefSeq	NP_001278885.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell-cell junction organization
Adherens junctions interactions
Cell junction organization
Cell-Cell communication

Biological Process

cell morphogenesis
cell-cell junction assembly
homophilic cell adhesion via plasma membrane adhesion molecules
calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules
adherens junction organization

Molecular Function

calcium ion binding
cytoskeletal protein binding
protein homodimerization activity
cadherin binding

Cellular Component

plasma membrane
cell-cell adherens junction
cell surface
integral component of membrane
catenin complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000507958
Coding exons: 11
Length: 1102923
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.808	395	443	0.892	0.0000233	5192
Missense (PolyPhen)		136	193.47	0.70294		2271
Synonymous	0.0709	162	163	0.993	0.00000914	1555
Loss of Function	3.78	7	28.9	0.242	0.00000129	397

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.;

Recessive Scores

pRec: 0.123

Intolerance Scores

LoFtool: 0.357
RVIS EVS: -1.22
RVIS percentile EVS: 5.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.794

Gene Damage Prediction

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