CDH22

protein-coding

cadherin 22, the group of Type II classical cadherins

Gene summary

This gene is a member of the cadherin superfamily. The gene product is composed of five cadherin repeat domains and a cytoplasmic tail similar to the highly conserved cytoplasmic region of classical cadherins. Expressed predominantly in the brain, this putative calcium-dependent cell adhesion protein may play an important role in morphogenesis and tissue formation in neural and non-neural cells during development and maintenance of the brain and neuroendocrine organs. [provided by RefSeq, Jul 2008]

Previous symbols:

C20orf25

MANE transcript

NM_021248.3

Inheritance

—

ClinVar variants

U:119B:4

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr20:46,173,739-46,308,498

External References & Databases

Ensembl (ENSG00000149654)

Transcript & Mutation Effects

hg38 • Region Span ~134.8 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 CDH22 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 3

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021248.3. 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 clinvar	1 clinvar	3
missense			115 clinvar	1 clinvar	1 clinvar	117
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	119	2	2	123

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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_021248.3	RefSeq	NP_067071.1	11	MANE Select
ENST00000537909.4	Ensembl	ENSP00000437790.1	11	MANE Select
ENST00000946368.1	Ensembl	ENSP00000616427.1	11	Standard
ENST00000946368.2	Ensembl	ENSP00000616427.1	11	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
brain development
calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules

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: ENST00000372262
Coding exons: 11
Length: 134766
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125746
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.78	333	510	0.653	0.0000330	5274
Missense (PolyPhen)		136	231.62	0.58718		2246
Synonymous	1.39	209	236	0.885	0.0000172	1744
Loss of Function	3.85	6	28.0	0.214	0.00000129	307

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00012	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000065	0.000065	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. PB-cadherins may have a role in the morphological organization of pituitary gland and brain tissues (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.226
RVIS EVS: -1.15
RVIS percentile EVS: 6.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.309

Gene Damage Prediction

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