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): 174 total
• GTEx eGene: eQTL in 20 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.03 (unconstrained)
• MANE Select transcript: NM_177980
• Notable: 174 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 9 — 7 protein_coding, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000348616

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 1, TSL 5: 2

ENST00000348616, ENST00000244049, ENST00000350849, ENST00000370991, ENST00000456106, ENST00000477058, ENST00000497614, ENST00000896767, ENST00001132561

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.

Highest expression (Bgee): bronchial epithelial cell, bronchus, lower esophagus mucosa, epithelium of nasopharynx, nasopharynx.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CDH26 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	9.6e-12	+0.89	20:59936932:A:C
Whole Blood	eqtl	4.5e-05	-0.40	20:59834176:C:T
Esophagus Muscularis	eqtl	7.0e-05	+0.70	20:59988428:C:T
Brain Putamen basal ganglia	eqtl	2.3e-04	+0.87	20:59988428:C:T
Brain Caudate basal ganglia	eqtl	3.5e-04	+0.88	20:59966676:T:C
Esophagus Gastroesophageal Junction	eqtl	1.4e-03	+0.64	20:59988428:C:T
Skin Sun Exposed Lower leg	eqtl	3.5e-03	+0.25	20:59862502:CTA:C
Artery Tibial	eqtl	8.3e-03	+0.50	20:59977182:C:T
Adipose Subcutaneous	eqtl	1.0e-02	-0.31	20:59889789:A:G
Skin Not Sun Exposed Suprapubic	eqtl	1.1e-02	+0.22	20:60431804:G:T
Thyroid	eqtl	1.4e-02	-0.35	20:59783536:A:G
Brain Hypothalamus	eqtl	2.2e-02	+0.81	20:60001394:T:G
Brain Hippocampus	eqtl	2.2e-02	+1.19	20:60711398:T:G
Brain Cerebellum	eqtl	2.5e-02	-0.74	20:59993317:G:A
Small Intestine Terminal Ileum	eqtl	2.6e-02	-1.49	20:59725497:A:C
Brain Nucleus accumbens basal ganglia	eqtl	3.0e-02	-1.46	20:59932995:G:A
Prostate	eqtl	3.8e-02	-0.57	20:60216880:C:T
Testis	eqtl	4.0e-02	-0.41	20:59997087:G:A
Stomach	eqtl	4.0e-02	+0.72	20:59958349:C:A
Brain Frontal Cortex BA9	eqtl	4.9e-02	+0.61	20:59988428:C:T

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

showing 100 of 254 tissues 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
urinary bladder	UBERON:0001255	69.58	gold quality
esophagus	UBERON:0001043	69.38	gold quality
adenohypophysis	UBERON:0002196	69.25	gold quality
myocardium	UBERON:0002349	69.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.01	gold quality
omental fat pad	UBERON:0010414	68.94	gold quality
saliva-secreting gland	UBERON:0001044	68.92	gold quality
peritoneum	UBERON:0002358	68.91	gold quality
apex of heart	UBERON:0002098	68.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	68.57	gold quality
pituitary gland	UBERON:0000007	68.51	gold quality
epithelial cell of pancreas	CL:0000083	68.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	68.42	gold quality
cerebellar hemisphere	UBERON:0002245	68.39	gold quality
sperm	CL:0000019	68.38	gold quality
leukocyte	CL:0000738	68.30	gold quality
cerebellar cortex	UBERON:0002129	68.24	gold quality
monocyte	CL:0000576	68.22	gold quality
adipose tissue of abdominal region	UBERON:0007808	68.16	gold quality
granulocyte	CL:0000094	68.13	gold quality
vagina	UBERON:0000996	67.85	gold quality
tibial nerve	UBERON:0001323	67.35	gold quality
ectocervix	UBERON:0012249	67.19	gold quality
cerebellum	UBERON:0002037	67.17	gold quality
spinal cord	UBERON:0002240	66.99	gold quality
uterine cervix	UBERON:0000002	66.69	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	66.39	gold quality
tonsil	UBERON:0002372	66.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.17	gold quality
muscle tissue	UBERON:0002385	66.12	gold quality
bone marrow	UBERON:0002371	66.07	gold quality
left uterine tube	UBERON:0001303	65.91	gold quality
gastrocnemius	UBERON:0001388	65.82	gold quality
lung	UBERON:0002048	65.82	gold quality
substantia nigra	UBERON:0002038	65.74	gold quality
muscle of leg	UBERON:0001383	65.67	gold quality
heart left ventricle	UBERON:0002084	65.57	gold quality
medial globus pallidus	UBERON:0002477	65.46	silver quality
cardiac ventricle	UBERON:0002082	65.30	gold quality
myometrium	UBERON:0001296	65.22	gold quality
putamen	UBERON:0001874	65.20	gold quality
skeletal muscle tissue	UBERON:0001134	65.18	gold quality
lymph node	UBERON:0000029	65.16	gold quality
quadriceps femoris	UBERON:0001377	64.91	gold quality
right frontal lobe	UBERON:0002810	64.84	gold quality
muscle layer of sigmoid colon	UBERON:0035805	64.84	gold quality
subcutaneous adipose tissue	UBERON:0002190	64.71	gold quality
kidney epithelium	UBERON:0004819	64.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	64.62	gold quality
midbrain	UBERON:0001891	64.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	64.52	gold quality
left coronary artery	UBERON:0001626	64.36	gold quality
smooth muscle tissue	UBERON:0001135	64.33	gold quality
cardiac atrium	UBERON:0002081	64.31	gold quality
caudate nucleus	UBERON:0001873	64.29	gold quality
adipose tissue	UBERON:0001013	64.24	gold quality
descending thoracic aorta	UBERON:0002345	64.19	gold quality
spleen	UBERON:0002106	64.17	gold quality
ascending aorta	UBERON:0001496	64.14	gold quality
skin of abdomen	UBERON:0001416	64.13	gold quality
body of uterus	UBERON:0009853	64.08	gold quality
amniotic fluid	UBERON:0000173	64.06	silver quality
heart	UBERON:0000948	64.03	gold quality
thoracic aorta	UBERON:0001515	64.02	gold quality
gall bladder	UBERON:0002110	63.96	gold quality
globus pallidus	UBERON:0001875	63.93	silver quality
right atrium auricular region	UBERON:0006631	63.89	gold quality
endothelial cell	CL:0000115	63.85	gold quality
coronary artery	UBERON:0001621	63.70	gold quality
lower esophagus	UBERON:0013473	63.68	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Prostate	tissue	7.5	low
Medulla oblongata	tissue	6.8
Putamen	tissue	5.6
Postcentral gyrus	tissue	5.5
Nucleus accumbens	tissue	5.2
Substantia nigra	tissue	4.9
Locus coeruleus	tissue	4.7
Spinal cord	tissue	4.7
Hippocampus	tissue	4.5	low
Retrosplenial cortex	tissue	4.3
Choroid plexus	tissue	3.9
Tonsil	tissue	2.8	high
Urinary bladder	tissue	2.5	medium
Basal ganglia	tissue	2.3	not detected
Septum	tissue	2.3
Cervix	tissue	1.9	medium
Thalamus	tissue	1.9
Lung	tissue	1.9	low
Fallopian tube	tissue	1.9	not detected
Esophagus	tissue	1.4	low
Pituitary gland	tissue	1.1
Stomach 1	tissue	1.1	medium
Bone marrow	tissue	1.0	not detected
Vagina	tissue	0.9	not detected
Skeletal muscle	tissue	0.9	not detected
Thymus	tissue	0.9
Adipose tissue	tissue	0.7	not detected
Corpus callosum	tissue	0.6
Breast	tissue	0.5	medium
Testis	tissue	0.5	medium
Seminal vesicle	tissue	0.5	medium
Pancreas	tissue	0.5	medium
Endometrium 1	tissue	0.5	low
Hippocampal formation	tissue	0.5
Lymph node	tissue	0.4	not detected
Smooth muscle	tissue	0.4	not detected
Epididymis	tissue	0.4	high
Placenta	tissue	0.4	low
Spleen	tissue	0.4	not detected
Small intestine	tissue	0.4	medium
Gallbladder	tissue	0.4	medium
Duodenum	tissue	0.4	low
Adrenal gland	tissue	0.4	low
Caudate putamen	tissue	0.4
Skin 1	tissue	0.3	not detected
Retina	tissue	0.3
Rectum	tissue	0.3	high
Tongue	tissue	0.3
Midbrain	tissue	0.3
Appendix	tissue	0.3	high
Heart muscle	tissue	0.2	not detected
Cerebral cortex	tissue	0.2	medium
Salivary gland	tissue	0.2	not detected
Parathyroid gland	tissue	0.2	medium
Colon	tissue	0.2	high
Frontal cortex	tissue	0.2
Amygdala	tissue	0.2
Hypothalamus	tissue	0.2
Thyroid gland	tissue	0.2	low
Liver	tissue	0.2	not detected

Brain sub-regions (HPA Brain Atlas): detected in 187; highest nTPM — Parieto-temporal junction (white matter) (8.5), Temporal white matter (8.4), Centromedial thalamic nucleus (7.3), Area striata (white matter) (7.2), Paraventricular nucleus (7.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CDH26 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 35 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 2.1e-21, LOEUF 1.03, missense Z 0.829 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000348616 — one region, missense o/e 0.98.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2685856) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased pulmonary ventilation	1
decreased pulmonary ventilation	1
decreased tidal volume	1
eye hemorrhage	1
decreased bronchoconstrictive response	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R9X1	99.4%	Diamond
Callithrix jacchus	B0KW95	99.0%	Diamond
Cricetulus griseus	O55075	98.3%	Diamond
Otolemur garnettii	B4USZ0	98.1%	Diamond
Rhinolophus ferrumequinum	B2KI42	97.6%	Diamond
Bos taurus	P19534	97.6%	Diamond
Xenopus laevis	P20310	95.9%	Diamond
Gallus gallus	P24503	94.6%	Diamond
Canis lupus familiaris	F1PAA9	82.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PHACTR3-AS1	ncRNA	100506384
PHACTR3	protein-coding	116154
PPP1R3D	protein-coding	5509
FAM217B	protein-coding	63939
SYCP2	protein-coding	10388
LINC02910	ncRNA	284756
MIR646HG	ncRNA	284757
MIR646	ncRNA	693231

Protein

Protein identifiers

Cadherin-like protein 26 — Q8IXH8 (reviewed: Q8IXH8)

Alternative names: Cadherin-like protein VR20

All UniProt accessions (3): H7BY79, Q8IXH8, 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; microtubules

Antibody reliability (HPA): IH uncertain · IF supported

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)

Type	Positions
N-linked (glcnac…) asparagine	81, 85, 171, 177, 462

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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

GO top-level categories

21 GO namespaces:

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
extrinsic component of plasma membrane	1
plasma membrane protein complex	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
CD4-positive, alpha-beta T cell activation	BP	direct assay
plasma membrane	CC	direct assay
alpha-catenin binding	MF	direct assay
beta-catenin binding	MF	direct assay
delta-catenin binding	MF	direct assay
integrin binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 352 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH26	CAPN14	A8MX76	568
CDH26	CCL26	Q9Y258	428
CDH26	CPA3	P15088	420
CDH26	PCSK6	P29122	412
CDH26	FBXL7	Q9UJT9	410
CDH26	CPA4	Q9UI42	390
CDH26	SLC9A3	P48764	347
CDH26	ALOX15	P16050	347
CDH26	METTL1	Q9UBP6	340
CDH26	GCNT3	O95395	314
CDH26	MAP3K14	Q99558	314
CDH26	GCNT4	Q9P109	313
CDH26	CDHR3	Q6ZTQ4	311
CDH26	POSTN	Q15063	304
CDH26	KIAA1210	Q9ULL0	304

IntAct

Human interaction partners of CDH26 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
MNAT1	physical association	0.400	1

BioGRID (4 interactions; top human partners by supporting records): HNRNPL (Affinity Capture-RNA), MNAT1 (Affinity Capture-MS), PARK2 (Affinity Capture-MS), VDAC1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for CDH26: 174 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	153
Likely benign	10
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 18 predictions of 1,896):

Position(s)	Effect	Δscore	Sites
20:59958796–59958797	donor_loss	1.0000	4
20:59984807	donor_gain	1.0000
20:59989159	donor_gain	1.0000
20:59992374–59992376	acceptor_gain	1.0000	2
20:59958796	donor_loss	0.9900
20:59971946	acceptor_gain	0.9900
20:59982921–59982922	acceptor_loss	0.9900	5
20:59984741	donor_gain	0.9900
20:59984998	acceptor_gain	0.9900
20:59985096	donor_gain	0.9900

AlphaMissense

656 missense substitutions predicted likely pathogenic (of 5,446 scored), across 199 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F218	8	0.886	0.978
D191	8	0.851	0.925
F106	8	0.846	0.974
D193	8	0.842	0.887
D249	8	0.835	0.921
N359	8	0.802	0.900
D300	8	0.775	0.896
D524	8	0.764	0.858
D302	8	0.737	0.828
F165	7	0.897	0.972
N159	7	0.875	0.941
F324	7	0.868	0.959
W56	7	0.859	0.943
W549	7	0.855	0.957
D160	7	0.838	0.888
F130	7	0.832	0.952
F71	7	0.826	0.952
D157	7	0.813	0.889
F534	7	0.802	0.925
C510	7	0.772	0.839

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	favorable	3.8e-05

Disease associations

OMIM: gene MIM:617685 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST005851_6	Delirium	5e-7
GCST008597_4	Fish intake frequency	5e-7

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0010139	fish consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, affects expression, increases abundance	3
Estradiol	increases expression, affects binding	3
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	affects binding, increases reaction	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 expression, increases abundance	1
Sodium Dodecyl Sulfate	increases expression	1
Antirheumatic Agents	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

12 trials:

NCT	Phase	Status	Title
NCT03414970	Phase 3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	Phase 2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	Phase 2	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	Phase 1/2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	Phase 1/2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	Early Phase 1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	Early Phase 1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT07628634	Early Phase 1	RECRUITING	Feasibility Study on the Effect of a Methionine-Reduced Diet on Serum Levels in Pts w/ Solid Tumors
NCT01208974	Not specified	COMPLETED	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