CDH19

protein-coding

cadherin 19, the group of Type II classical cadherins

Gene summary

This gene is one of three related type II cadherin genes situated in a cluster on chromosome 18. The encoded protein is a calcium dependent cell-cell adhesion glycoprotein containing five extracellular cadherin repeats. Loss of cadherins may be associated with cancer formation. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Aug 2012]

MANE transcript

NM_021153.4

Inheritance

—

ClinVar variants

U:117B:18

Top phenotype

CDH19-related disorder

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr18:66,501,083-66,604,138

External References & Databases

Ensembl (ENSG00000071991)

Transcript & Mutation Effects

hg38 • Region Span ~103.1 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 CDH19 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 109

CDH19-related disorderTotal: 23

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021153.4. 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			3 clinvar	1 clinvar	4 clinvar	8
missense			113 clinvar	7 clinvar	6 clinvar	126
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	117	8	10	135

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021153.4	RefSeq	NP_066976.1	11	MANE Select
ENST00000262150.7	Ensembl	ENSP00000262150.2	11	MANE Select
NM_001271028.2	RefSeq	NP_001257957.1	9	Standard
ENST00000454642.3	Ensembl	ENSP00000401998.3	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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: ENST00000262150
Coding exons: 11
Length: 103056
Individuals with no LoFs: 125631
Homozygous LoFs: 2
Heterozygous LoFs: 115
Defined: 125748
p: 0.000465

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.708	450	410	1.10	0.0000202	5094
Missense (PolyPhen)		174	150.14	1.1589		1895
Synonymous	-1.56	170	146	1.16	0.00000763	1431
Loss of Function	1.03	25	31.2	0.801	0.00000149	402

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.00036	0.00035	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00050	0.00049	rare
Finnish	0.000095	0.000092	rare
European (Non-Finnish)	0.00031	0.00028	rare
South Asian	0.0018	0.0017	notable
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: 0.0956

Intolerance Scores

LoFtool: 0.798
RVIS EVS: 1.4
RVIS percentile EVS: 94.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0985

Gene Damage Prediction

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