CDH9

protein-coding

cadherin 9, 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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_016279.4

Inheritance

—

ClinVar variants

U:88B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr5:26,880,597-27,121,150

External References & Databases

Ensembl (ENSG00000113100)

Transcript & Mutation Effects

hg38 • Region Span ~240.6 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 CDH9 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 85

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016279.4. 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			1 clinvar	2 clinvar	1 clinvar	4
missense			87 clinvar		2 clinvar	89
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	88	2	3	93

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016279.4	RefSeq	NP_057363.3	11	MANE Select
ENST00000231021.9	Ensembl	ENSP00000231021.4	11	MANE Select
ENST00000511822.1	Ensembl	ENSP00000422538.1	2	Standard
ENST00000513289.5	Ensembl	ENSP00000426239.1	2	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
synapse assembly
calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules

Molecular Function

molecular_function
calcium ion binding
cytoskeletal protein binding
protein homodimerization activity
cadherin binding

Cellular Component

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000231021
Coding exons: 11
Length: 240549
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125738
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.76	345	450	0.767	0.0000246	5243
Missense (PolyPhen)		128	206.47	0.61993		2396
Synonymous	-2.81	209	163	1.28	0.00000961	1476
Loss of Function	4.29	6	32.3	0.186	0.00000168	402

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	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: 0.0943

Intolerance Scores

LoFtool: 0.353
RVIS EVS: -0.38
RVIS percentile EVS: 28.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.876

Gene Damage Prediction

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