CDH8

protein-coding

cadherin 8, the group of Type II classical cadherins

Gene summary

This gene encodes a type II classical cadherin from the cadherin superfamily, 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. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. 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 in brain and is putatively involved in synaptic adhesion, axon outgrowth and guidance. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001796.5

Inheritance

—

ClinVar variants

U:79B:10

Top phenotype

See cases

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr16:61,647,242-62,037,035

External References & Databases

Ensembl (ENSG00000150394)

Transcript & Mutation Effects

hg38 • Region Span ~389.8 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 CDH8 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 73

not providedTotal: 12

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001796.5. 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				6 clinvar	2 clinvar	8
missense			77 clinvar	2 clinvar		79
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	0	0	79	8	2	89

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001796.5	RefSeq	NP_001787.2	11	MANE Select
ENST00000577390.6	Ensembl	ENSP00000462701.1	11	MANE Select
NM_001410893.1	RefSeq	NP_001397822.1	8	Standard
ENST00000299345.10	Ensembl	ENSP00000299345.6	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

cell morphogenesis
cell-cell junction assembly
cell adhesion
homophilic cell adhesion via plasma membrane adhesion molecules
response to cold

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: ENST00000577390
Coding exons: 11
Length: 389794
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125748
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.42	315	461	0.683	0.0000253	5266
Missense (PolyPhen)		107	196.3	0.54508		2198
Synonymous	-0.592	185	175	1.06	0.0000102	1574
Loss of Function	4.49	4	31.0	0.129	0.00000165	381

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	0.000033	0.000033	rare
Other	0	0.0	absent

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: 0.194
RVIS EVS: -0.49
RVIS percentile EVS: 22.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.815

Gene Damage Prediction

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