CDH26

Summary

CDH26 (cadherin 26, HGNC:15902) is a protein-coding gene on chromosome 20q13.33, encoding Cadherin-like protein 26 (Q8IXH8). Cadherins are calcium-dependent cell adhesion proteins.

This gene encodes a member of the cadherin protein family. Cadherins are a family of calcium-dependent adhesion molecules that mediate cell-cell adhesion in all solid tissues and modulate a wide variety of processes, including cell polarization, migration and differentiation. Cadherin domains occur as repeats in the extracellular region and are thought to contribute to the sorting of heterogeneous cell types and the maintenance of orderly structures such as epithelium. This protein is expressed in gastrointestinal epithelial cells and may be upregulated during allergic inflammation. This protein interacts with alpha integrins and may also be involved in leukocyte migration and adhesion.

Source: NCBI Gene 60437 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 172 total
• MANE Select transcript: NM_177980

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15902
Approved symbol	CDH26
Name	cadherin 26
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	VR20
Ensembl gene	ENSG00000124215
Ensembl biotype	protein_coding
OMIM	617685
Entrez	60437

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000244049, ENST00000348616, ENST00000350849, ENST00000370991, ENST00000456106, ENST00000477058, ENST00000497614, ENST00000896767

RefSeq mRNA: 3 — MANE Select: NM_177980 NM_001348204, NM_021810, NM_177980

CCDS: CCDS13485, CCDS13486, CCDS86964

Canonical transcript exons

ENST00000348616 — 18 exons

Exon	Start	End
ENSE00001029949	60001343	60001411
ENSE00001599147	59982923	59983070
ENSE00001623472	59994250	59994489
ENSE00001623525	59971962	59972123
ENSE00001634787	59985001	59985129
ENSE00001642296	59968967	59969023
ENSE00001655117	59988904	59989163
ENSE00001662384	59970082	59970186
ENSE00001750902	59992378	59992520
ENSE00001790884	59984639	59984805
ENSE00001834742	60012527	60014529
ENSE00002262024	59958423	59958795
ENSE00003484685	59996631	59996761
ENSE00003497486	59987453	59987638
ENSE00003519266	59995833	59996054
ENSE00003602232	60002813	60002866
ENSE00003649916	60006713	60006787
ENSE00003660929	59999586	59999663

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 95.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2088 / max 71.7739, expressed in 67 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185653	0.1566	47
185650	0.0243	13
185652	0.0206	12
185651	0.0046	1
185654	0.0027	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	95.81	gold quality
bronchus	UBERON:0002185	94.20	gold quality
lower esophagus mucosa	UBERON:0035834	89.10	gold quality
epithelium of nasopharynx	UBERON:0001951	88.07	gold quality
nasopharynx	UBERON:0001728	88.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.34	gold quality
upper arm skin	UBERON:0004263	83.61	gold quality
prostate gland	UBERON:0002367	82.06	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.00	gold quality
tibialis anterior	UBERON:0001385	80.42	silver quality
buccal mucosa cell	CL:0002336	78.99	silver quality
oral cavity	UBERON:0000167	78.12	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.02	gold quality
esophagus mucosa	UBERON:0002469	74.79	gold quality
right lung	UBERON:0002167	74.76	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.48	gold quality
nasal cavity mucosa	UBERON:0001826	74.47	gold quality
left ventricle myocardium	UBERON:0006566	74.32	gold quality
ileal mucosa	UBERON:0000331	73.81	silver quality
minor salivary gland	UBERON:0001830	73.51	gold quality
esophagus squamous epithelium	UBERON:0006920	73.41	gold quality
pancreatic ductal cell	CL:0002079	72.71	silver quality
deltoid	UBERON:0001476	71.79	silver quality
endocervix	UBERON:0000458	71.62	gold quality
mouth mucosa	UBERON:0003729	71.49	gold quality
right uterine tube	UBERON:0001302	71.40	gold quality
upper lobe of left lung	UBERON:0008952	71.25	gold quality
corpus callosum	UBERON:0002336	71.08	gold quality
blood	UBERON:0000178	70.33	gold quality
upper lobe of lung	UBERON:0008948	70.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting CDH26, 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-12118	100.00	65.88	1270
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-5571-3P	97.80	66.07	640
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-517-5P	97.13	68.43	781

Literature-anchored findings (GeneRIF, showing 3)

• this study shows that cadherin 26 is an alpha integrin-binding epithelial receptor regulated during allergic inflammation (PMID:28051089)
• Epithelial cell-adhesion protein cadherin 26 is dysregulated in congenital diaphragmatic hernia and congenital pulmonary airway malformation. (PMID:33161446)
• Knockdown of Cadherin 26 Prevents the Inflammatory Responses of Allergic Rhinitis. (PMID:36069256)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdh26.1	ENSDARG00000078404
mus_musculus	Cdh26	ENSMUSG00000039155
rattus_norvegicus	Cdh26	ENSRNOG00000053332

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), CDHR3 (ENSG00000128536), CDH15 (ENSG00000129910), CDH24 (ENSG00000139880), CDH11 (ENSG00000140937), CDH13 (ENSG00000140945), CDH18 (ENSG00000145526), CDHR1 (ENSG00000148600), CDH22 (ENSG00000149654), 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-like protein 26 — Q8IXH8 (reviewed: Q8IXH8)

Alternative names: Cadherin-like protein VR20

All UniProt accessions (3): Q8IXH8, H7BY79, Q9NTY2

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. Ligand for integrins alpha-E/beta-7, ITGAE:ITGAB7, alpha-4/beta-7, ITGA4:ITGAB7 and alpha-4/beta-1, ITGA4:ITGAB1 through which modulates CD4(+) T cells activation.

Subunit / interactions. Homodimer. Component of a cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed by epithelial cells of gastrointestinal tissue.

Post-translational modifications. N-glycosylated.

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.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8IXH8-4	3	yes
Q8IXH8-1	1, a
Q8IXH8-2	2, b
Q8IXH8-5	4

RefSeq proteins (3): NP_001335133, NP_068582, NP_817089* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR039808	Cadherin	Family

Pfam: PF00028

UniProt features (24 total): glycosylation site 5, sequence variant 5, splice variant 4, domain 4, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXH8-F1	72.84	0.45

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 (5): 81, 85, 171, 177, 462

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_CALCIUM_DEPENDENT_CELL_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_CD4_POSITIVE_ALPHA_BETA_T_CELL_ACTIVATION, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_ADHERENS_JUNCTION_ORGANIZATION, GOBP_CELL_CELL_JUNCTION_ASSEMBLY, GOMF_SIGNALING_RECEPTOR_BINDING, GOCC_CELL_CELL_JUNCTION, NOUZOVA_METHYLATED_IN_APL, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_ANCHORING_JUNCTION

GO Biological Process (10): 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), CD4-positive, alpha-beta T cell activation (GO:0035710), cell-cell adhesion mediated by cadherin (GO:0044331), cell adhesion (GO:0007155), cell-cell adhesion (GO:0098609)

GO Molecular Function (8): integrin binding (GO:0005178), calcium ion binding (GO:0005509), beta-catenin binding (GO:0008013), alpha-catenin binding (GO:0045294), cadherin binding (GO:0045296), delta-catenin binding (GO:0070097), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): plasma membrane (GO:0005886), adherens junction (GO:0005912), microtubule cytoskeleton (GO:0015630), catenin complex (GO:0016342), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	3
protein binding	3
cell-cell junction organization	2
cell adhesion molecule binding	2
anatomical structure morphogenesis	1
cell junction assembly	1
cell motility	1
alpha-beta T cell activation	1
cellular process	1
cell adhesion	1
signaling receptor binding	1
protein-containing complex binding	1
metal ion binding	1
binding	1
cation binding	1
membrane	1
cell periphery	1
cell-cell junction	1
cytoskeleton	1
extrinsic component of plasma membrane	1
plasma membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH26	CAPN14	A8MX76	584
CDH26	CCL26	Q9Y258	462
CDH26	FBXL7	Q9UJT9	437
CDH26	METTL1	Q9UBP6	404
CDH26	ALOX15	P16050	367
CDH26	CPA3	P15088	358
CDH26	CPA4	Q9UI42	348
CDH26	CTNNAL1	Q9UBT7	346
CDH26	SLC9A3	P48764	335
CDH26	PCSK6	P29122	328
CDH26	CDHR3	Q6ZTQ4	310
CDH26	MAP3K14	Q99558	306
CDH26	POSTN	Q15063	304
CDH26	TPSD1	Q9BZJ3	277
CDH26	TUSC1	Q2TAM9	277

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CDH26	MNAT1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (3): CDH26 (Affinity Capture-RNA), MNAT1 (Affinity Capture-MS), CDH26 (Affinity Capture-MS)

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: 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, P33147, P33148, P33150, P33151, P33152, P33545, P39038, P55280, P55283, P55284, P55285, P55286

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	151
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3237 predictions. Top by Δscore:

Variant	Effect	Δscore
20:59958796:GTAAG:G	donor_loss	1.0000
20:59958797:T:A	donor_loss	1.0000
20:59984807:T:G	donor_gain	1.0000
20:59985126:GAAC:G	donor_gain	1.0000
20:59985130:G:GG	donor_gain	1.0000
20:59989159:A:G	donor_gain	1.0000
20:59992373:A:AG	acceptor_gain	1.0000
20:59992374:C:G	acceptor_gain	1.0000
20:59992375:A:AG	acceptor_gain	1.0000
20:59992376:A:G	acceptor_gain	1.0000
20:59992377:GATAT:G	acceptor_gain	1.0000
20:59995940:G:GG	donor_gain	1.0000
20:59999655:GGAGT:G	donor_gain	1.0000
20:59966523:T:TA	acceptor_gain	0.9900
20:59971946:T:G	acceptor_gain	0.9900
20:59982440:TACAG:T	donor_gain	0.9900
20:59982441:ACAGA:A	donor_gain	0.9900
20:59982917:TCCTA:T	acceptor_loss	0.9900
20:59982919:CTA:C	acceptor_loss	0.9900
20:59982920:TA:T	acceptor_loss	0.9900
20:59982921:A:G	acceptor_loss	0.9900
20:59982922:G:A	acceptor_loss	0.9900
20:59983034:G:GT	donor_gain	0.9900
20:59984741:A:T	donor_gain	0.9900
20:59984998:T:G	acceptor_gain	0.9900
20:59985096:C:T	donor_gain	0.9900
20:59985124:G:GT	donor_gain	0.9900
20:59985125:A:T	donor_gain	0.9900
20:59985127:A:T	donor_gain	0.9900
20:59985135:GCTCC:G	donor_gain	0.9900

AlphaMissense

5446 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:59984749:T:C	F218L	0.978
20:59984751:C:A	F218L	0.978
20:59984751:C:G	F218L	0.978
20:59972047:T:C	F106S	0.974
20:59983022:T:C	F165L	0.972
20:59983024:T:A	F165L	0.972
20:59983024:T:G	F165L	0.972
20:59984750:T:C	F218S	0.969
20:59985074:T:A	V261D	0.967
20:59987625:T:C	L337S	0.963
20:59987585:T:C	F324L	0.959
20:59987587:T:A	F324L	0.959
20:59987587:T:G	F324L	0.959
20:59994470:G:C	W549C	0.957
20:59994470:G:T	W549C	0.957
20:59984750:T:G	F218C	0.955
20:59994429:T:C	F536L	0.955
20:59994431:T:A	F536L	0.955
20:59994431:T:G	F536L	0.955
20:59972101:G:C	R124P	0.953
20:59970166:T:C	F71L	0.952
20:59970168:T:A	F71L	0.952
20:59970168:T:G	F71L	0.952
20:59972118:T:C	F130L	0.952
20:59972120:C:A	F130L	0.952
20:59972120:C:G	F130L	0.952
20:59983023:T:C	F165S	0.950
20:59985013:T:C	F241L	0.950
20:59985015:T:A	F241L	0.950
20:59985015:T:G	F241L	0.950

dbSNP variants (sampled 300 via entrez): RS1000026614 (20:60027205 A>G,T), RS1000037434 (20:59970536 C>T), RS1000043285 (20:59992018 G>A), RS1000109487 (20:60006164 C>T), RS1000131931 (20:59979274 C>T), RS1000133034 (20:60020902 G>A), RS1000165946 (20:59979195 T>C), RS1000166251 (20:60021133 G>A,T), RS1000240212 (20:59991745 G>A), RS1000277277 (20:60013630 T>C), RS1000284744 (20:59973106 G>A), RS1000295992 (20:60032665 G>A), RS1000306133 (20:60013975 C>T), RS1000307637 (20:60027387 C>T), RS1000325525 (20:60008845 G>T)

Disease associations

OMIM: gene MIM:617685 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005851_8	Delirium	5.000000e-07
GCST008597_4	Fish intake frequency	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010139	fish consumption measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, increases expression	3
Air Pollutants	affects expression, increases abundance, increases expression	2
butyraldehyde	decreases expression	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
Allergens	increases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	decreases expression, decreases reaction	1
Ozone	affects expression, increases abundance	1
Smoke	increases abundance, increases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Antirheumatic Agents	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery