CDH22

Summary

CDH22 (cadherin 22, HGNC:13251) is a protein-coding gene on chromosome 20q13.12, encoding Cadherin-22 (Q9UJ99). Cadherins are calcium-dependent cell adhesion proteins.

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.

Source: NCBI Gene 64405 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 126 total
• MANE Select transcript: NM_021248

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13251
Approved symbol	CDH22
Name	cadherin 22
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ998H6.1
Ensembl gene	ENSG00000149654
Ensembl biotype	protein_coding
OMIM	609920
Entrez	64405

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000474438, ENST00000537909, ENST00000946368, ENST00000946369, ENST00000946370

RefSeq mRNA: 1 — MANE Select: NM_021248 NM_021248

CCDS: CCDS13395

Canonical transcript exons

ENST00000537909 — 12 exons

Exon	Start	End
ENSE00000906926	46177946	46178197
ENSE00000906927	46186588	46186705
ENSE00000906928	46186826	46186947
ENSE00000906929	46199423	46199559
ENSE00000906933	46227508	46227627
ENSE00000906934	46240963	46241257
ENSE00001043481	46210307	46210560
ENSE00001457376	46173739	46175077
ENSE00002231316	46308255	46308498
ENSE00002320582	46251040	46251693
ENSE00003561952	46216826	46216993
ENSE00003641751	46212995	46213188

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 94.66.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5114 / max 309.6971, expressed in 218 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187548	0.5543	111
187550	0.4693	130
187551	0.1775	68
187547	0.1535	66
187552	0.1123	53
187549	0.0332	21
209149	0.0113	4

Top tissues by expression

252 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	94.66	gold quality
paraflocculus	UBERON:0005351	94.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.43	gold quality
cerebellar cortex	UBERON:0002129	92.04	gold quality
cerebellum	UBERON:0002037	91.99	gold quality
cerebellar hemisphere	UBERON:0002245	91.95	gold quality
endothelial cell	CL:0000115	89.85	gold quality
Brodmann (1909) area 10	UBERON:0013541	87.51	gold quality
vena cava	UBERON:0004087	86.68	silver quality
frontal pole	UBERON:0002795	85.49	gold quality
middle temporal gyrus	UBERON:0002771	85.39	gold quality
right frontal lobe	UBERON:0002810	84.56	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.84	gold quality
superior frontal gyrus	UBERON:0002661	82.73	gold quality
frontal cortex	UBERON:0001870	82.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.36	gold quality
parotid gland	UBERON:0001831	82.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.00	gold quality
Brodmann (1909) area 23	UBERON:0013554	81.98	gold quality
neocortex	UBERON:0001950	81.60	gold quality
prefrontal cortex	UBERON:0000451	81.57	gold quality
occipital lobe	UBERON:0002021	81.56	gold quality
primary visual cortex	UBERON:0002436	81.40	gold quality
cingulate cortex	UBERON:0003027	81.21	gold quality
anterior cingulate cortex	UBERON:0009835	81.11	gold quality
orbitofrontal cortex	UBERON:0004167	81.08	gold quality
temporal lobe	UBERON:0001871	81.03	gold quality
parietal lobe	UBERON:0001872	80.95	gold quality
nipple	UBERON:0002030	80.94	silver quality
ventral tegmental area	UBERON:0002691	80.89	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	5.80
E-ANND-3	no	1.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting CDH22, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-455-5P	98.74	67.31	795
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-1227-3P	97.36	66.94	834
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048

Literature-anchored findings (GeneRIF, showing 5)

• PRL-3 promoted downregulation of CDH22 expression. (PMID:19440036)
• Our results reveal for the first time a new role of CDH22 in progression of colorectal cancer. (PMID:19546606)
• Results present evidence that CDH22 is hypermethylated and its expression is downregulated in breast cancer. (PMID:28149335)
• cadherin-22 is upregulated in hypoxia via mTORC1-independent translational control by the initiation factor eIF4E2 functioning as a hypoxia-specific cell-surface molecule involved in cancer cell migration, invasion and adhesion. (PMID:28991229)
• This paper deals primarily with the rat ortholog of the human CDH22 gene. (PMID:8626716)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdh22	ENSDARG00000098824
mus_musculus	Cdh22	ENSMUSG00000053166
rattus_norvegicus	Cdh22	ENSRNOG00000018557

Paralogs (33): CDH1 (ENSG00000039068), CDH10 (ENSG00000040731), CDH3 (ENSG00000062038), CDH19 (ENSG00000071991), CDHR2 (ENSG00000074276), CDH17 (ENSG00000079112), CDH7 (ENSG00000081138), PCDH11Y (ENSG00000099715), CDHR5 (ENSG00000099834), CDH20 (ENSG00000101542), PCDH11X (ENSG00000102290), CDH23 (ENSG00000107736), CDH9 (ENSG00000113100), CDH6 (ENSG00000113361), CDH26 (ENSG00000124215), CDHR3 (ENSG00000128536), CDH15 (ENSG00000129910), CDH24 (ENSG00000139880), CDH11 (ENSG00000140937), CDH13 (ENSG00000140945), CDH18 (ENSG00000145526), CDHR1 (ENSG00000148600), CDH8 (ENSG00000150394), CDH12 (ENSG00000154162), PCDH1 (ENSG00000156453), DCHS1 (ENSG00000166341), PCDH7 (ENSG00000169851), CDH2 (ENSG00000170558), CDH4 (ENSG00000179242), CDH5 (ENSG00000179776), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410), PCDH20 (ENSG00000280165)

Protein

Protein identifiers

Cadherin-22 — Q9UJ99 (reviewed: Q9UJ99)

Alternative names: Pituitary and brain cadherin

All UniProt accessions (1): Q9UJ99

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Cell membrane.

Domain organisation. Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.

RefSeq proteins (1): NP_067071* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000233	Cadherin_Y-type_LIR	Domain
IPR002126	Cadherin-like_dom	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR027397	Catenin-bd_sf	Homologous_superfamily
IPR039808	Cadherin	Family

Pfam: PF00028, PF01049

UniProt features (15 total): domain 5, glycosylation site 3, topological domain 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJ99-F1	76.19	0.44

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (3): 162, 466, 612

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): MODULE_255, MODULE_317, GOBP_CALCIUM_DEPENDENT_CELL_CELL_ADHESION, MODULE_66, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION, OCT1_03, GOBP_CELL_JUNCTION_ASSEMBLY, CCCAGAG_MIR326, GOBP_ADHERENS_JUNCTION_ORGANIZATION, GOBP_CELL_CELL_JUNCTION_ASSEMBLY, GOCC_CELL_CELL_JUNCTION, MODULE_11, GOCC_MEMBRANE_PROTEIN_COMPLEX, MODULE_69

GO Biological Process (9): cell morphogenesis (GO:0000902), cell-cell junction assembly (GO:0007043), homophilic cell-cell adhesion (GO:0007156), calcium-dependent cell-cell adhesion (GO:0016339), cell migration (GO:0016477), adherens junction organization (GO:0034332), cell-cell adhesion mediated by cadherin (GO:0044331), cell adhesion (GO:0007155), cell-cell adhesion (GO:0098609)

GO Molecular Function (4): calcium ion binding (GO:0005509), beta-catenin binding (GO:0008013), cadherin binding (GO:0045296), metal ion binding (GO:0046872)

GO Cellular Component (4): adherens junction (GO:0005912), catenin complex (GO:0016342), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	3
cell-cell junction organization	2
anatomical structure morphogenesis	1
cell junction assembly	1
cell motility	1
cellular process	1
cell adhesion	1
metal ion binding	1
protein binding	1
cell adhesion molecule binding	1
cation binding	1
cell-cell junction	1
extrinsic component of plasma membrane	1
plasma membrane protein complex	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH22	CTNNB1	P35222	731
CDH22	K7ELQ4	K7ELQ4	561
CDH22	NCOA5	Q9HCD5	509
CDH22	ATF7	P17544	463
CDH22	SLC35D4	Q24JQ0	460
CDH22	CFAP20DC	Q6ZVT6	447
CDH22	NTNG2	Q96CW9	406
CDH22	ANKRD29	Q8N6D5	398
CDH22	PEX11A	O75192	385
CDH22	GLRX2	Q9NS18	383
CDH22	KLHL35	Q6PF15	382
CDH22	EIF4E2	O60573	371
CDH22	EEF2	P13639	354
CDH22	ITGA1	P56199	351
CDH22	DNTTIP1	Q9H147	349

IntAct

0 interactions, top by confidence:

BioGRID (2): CDH22 (Positive Genetic), CDH22 (Reconstituted Complex)

ESM2 similar proteins: A0A140LHF2, A6H8M9, D3YX43, O08644, O15197, O55134, O70394, O70540, O75309, O88338, P0C091, P0C0K6, P0C0K7, P0DP72, P21709, P40223, P59862, P70289, Q00657, Q04912, Q0V8J4, Q28634, Q501P1, Q53RD9, Q58Y75, Q5DRE2, Q5H8B9, Q5R6F5, Q5SZK8, Q60750, Q63315, Q64612, Q6MG64, Q6NVD0, Q6PFX6, Q6UVK1, Q76MJ5, Q7TN88, Q7Z442, Q86UP0

Diamond homologs: A0A1S4GGP7, Q5DRC7, Q5DRD9, Q5DRE2, Q5R9Q9, Q91XZ2, Q91Y13, Q9H158, Q9UJ99, Q9UN67, Q9VJB6, Q9Y5E2, A0A8M2BIB6, B0KW95, B2KI42, B4USZ0, F1PAA9, F1QSQ0, O02840, O35902, O54800, O55075, O55111, O93319, P08641, P09803, P10287, P10288, P12830, P15116, P19022, P19534, P19535, P20310, P22223, P24503, P30944, P32926, P33145, P33146

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
calcium(2+)	“up-regulates activity”	CDH22	“chemical activation”
CDH22	“up-regulates activity”	CTNNB1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

126 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1712 predictions. Top by Δscore:

Variant	Effect	Δscore
20:46175073:CAGCA:C	acceptor_gain	1.0000
20:46175074:AGCA:A	acceptor_gain	1.0000
20:46175075:GCA:G	acceptor_gain	1.0000
20:46175076:CA:C	acceptor_gain	1.0000
20:46175076:CAC:C	acceptor_gain	1.0000
20:46175077:ACTGC:A	acceptor_loss	1.0000
20:46175078:C:CC	acceptor_gain	1.0000
20:46186582:GCTCA:G	donor_loss	1.0000
20:46186583:CTCAC:C	donor_loss	1.0000
20:46186584:TCA:T	donor_loss	1.0000
20:46186585:CA:C	donor_loss	1.0000
20:46186586:A:AG	donor_loss	1.0000
20:46186587:C:CA	donor_loss	1.0000
20:46186702:TGAG:T	acceptor_gain	1.0000
20:46186706:C:CC	acceptor_gain	1.0000
20:46186713:G:C	acceptor_gain	1.0000
20:46186713:G:GC	acceptor_gain	1.0000
20:46186842:T:TA	donor_gain	1.0000
20:46186944:TTGT:T	acceptor_gain	1.0000
20:46186945:TGT:T	acceptor_gain	1.0000
20:46186948:C:CC	acceptor_gain	1.0000
20:46210556:AGGCG:A	acceptor_gain	1.0000
20:46210557:GGCG:G	acceptor_gain	1.0000
20:46210558:GCG:G	acceptor_gain	1.0000
20:46210558:GCGC:G	acceptor_loss	1.0000
20:46210559:CG:C	acceptor_gain	1.0000
20:46210559:CGC:C	acceptor_gain	1.0000
20:46210560:GCTG:G	acceptor_loss	1.0000
20:46210561:C:CC	acceptor_gain	1.0000
20:46210562:T:C	acceptor_loss	1.0000

AlphaMissense

5383 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:46213087:A:C	Y314D	1.000
20:46213113:T:A	D305V	1.000
20:46213113:T:C	D305G	1.000
20:46213113:T:G	D305A	1.000
20:46213114:C:G	D305H	1.000
20:46213119:T:G	D303A	1.000
20:46213120:C:G	D303H	1.000
20:46213125:G:T	A301D	1.000
20:46216834:A:G	F277S	1.000
20:46216840:G:C	P275R	1.000
20:46216840:G:T	P275H	1.000
20:46216849:T:A	D272V	1.000
20:46216849:T:C	D272G	1.000
20:46216849:T:G	D272A	1.000
20:46216850:C:G	D272H	1.000
20:46216851:A:C	N271K	1.000
20:46216851:A:T	N271K	1.000
20:46216859:C:G	D269H	1.000
20:46216870:A:T	I265N	1.000
20:46216876:A:T	V263D	1.000
20:46216930:A:T	I245N	1.000
20:46216960:C:G	R235P	1.000
20:46216987:A:T	I226N	1.000
20:46227528:A:G	F217S	1.000
20:46241010:A:G	F168S	1.000
20:46241016:G:T	P166H	1.000
20:46241025:T:G	D163A	1.000
20:46241027:A:C	N162K	1.000
20:46241027:A:T	N162K	1.000
20:46241033:G:C	D160E	1.000

dbSNP variants (sampled 300 via entrez): RS1000005946 (20:46198207 G>A), RS1000006263 (20:46201551 A>T), RS1000026411 (20:46287616 G>T), RS1000030502 (20:46246867 T>G), RS1000038775 (20:46269553 G>A), RS1000049063 (20:46228530 T>G), RS1000072606 (20:46282157 G>A), RS1000089059 (20:46269912 G>T), RS1000110990 (20:46237644 C>A,G,T), RS1000112387 (20:46179523 C>T), RS1000136741 (20:46309908 G>A,C), RS1000172161 (20:46210705 G>A,C,T), RS1000181929 (20:46293877 T>C), RS1000212755 (20:46293606 C>T), RS1000214352 (20:46294255 T>C)

Disease associations

OMIM: gene MIM:609920 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005359_27	Disease progression in age-related macular degeneration	9.000000e-06
GCST006448_3	Eye movement in schizophrenia (horizontal position gain)	2.000000e-08
GCST010136_52	Fruit consumption	4.000000e-09
GCST010988_326	Adult body size	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Silicon Dioxide	increases expression, decreases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
MRK 003	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Troglitazone	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Testosterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.