CDH12

Summary

CDH12 (cadherin 12, HGNC:1751) is a protein-coding gene on chromosome 5p14.3, encoding Cadherin-12 (P55289). Cadherins are calcium-dependent cell adhesion proteins.

This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature cadherin protein. These integral membrane proteins mediate calcium-dependent cell-cell adhesion and are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. This particular cadherin appears to be expressed specifically in the brain and its temporal pattern of expression would be consistent with a role during a critical period of neuronal development, perhaps specifically during synaptogenesis.

Source: NCBI Gene 1010 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 167 total — 1 pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 14 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.67 (unconstrained)
• MANE Select transcript: NM_004061
• Notable: 167 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1751
Approved symbol	CDH12
Name	cadherin 12
Location	5p14.3
Locus type	gene with protein product
Status	Approved
Aliases	Br-cadherin, CDHB
Ensembl gene	ENSG00000154162
Ensembl biotype	protein_coding
OMIM	600562
Entrez	1010

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000382254

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 1, TSL 4: 2, TSL 5: 1

ENST00000382254, ENST00000504376, ENST00000517378, ENST00000518209, ENST00000520668, ENST00000521384, ENST00000521745, ENST00000522262, ENST00000880753, ENST00000954356, ENST00001131005

RefSeq mRNA: 9 — MANE Select: NM_004061 NM_001317227, NM_001317228, NM_001364104, NM_001364105, NM_001364106, NM_001364107, NM_001364108, NM_001364109, NM_004061

CCDS: CCDS3890, CCDS82991

Canonical transcript exons

ENST00000382254 — 15 exons

Exon	Start	End
ENSE00001402656	22212498	22212643
ENSE00001404736	22505270	22505364
ENSE00001406275	22405257	22405351
ENSE00002072306	21750673	21752236
ENSE00003462950	21842161	21842328
ENSE00003462989	21802167	21802420
ENSE00003465765	21760558	21760675
ENSE00003525376	22078446	22078862
ENSE00003529986	21764978	21765099
ENSE00003535159	21975091	21975385
ENSE00003625935	21783358	21783494
ENSE00003632046	21755591	21755842
ENSE00003675761	21816945	21817132
ENSE00003694264	21854671	21854790
ENSE00004782469	22853058	22853344

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 78.25.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7445 / max 229.6578, expressed in 127 samples.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, middle temporal gyrus, postcentral gyrus, adrenal tissue, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CDH12 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellar Hemisphere	eqtl	3.0e-17	+0.59	5:22382472:G:A
Brain Cerebellum	eqtl	8.0e-15	+0.62	5:22382472:G:A
Brain Spinal cord cervical c-1	eqtl	2.0e-13	-0.86	5:22176168:T:C
Adipose Subcutaneous	eqtl	2.7e-07	-0.27	5:22698434:T:C
Adrenal Gland	eqtl	1.3e-05	-0.39	5:21888596:TA:T
Testis	eqtl	7.8e-05	-0.37	5:22208822:A:G
Uterus	eqtl	1.1e-04	-0.54	5:22182234:G:A
Skin Sun Exposed Lower leg	eqtl	1.2e-03	+0.17	5:22228799:TA:T
Brain Caudate basal ganglia	eqtl	5.0e-03	-0.11	5:22744323:G:A
Skin Not Sun Exposed Suprapubic	eqtl	7.7e-03	+0.17	5:22225803:A:G
Brain Frontal Cortex BA9	eqtl	2.2e-02	-0.72	5:21919601:A:G
Breast Mammary Tissue	eqtl	2.5e-02	-0.19	5:22683551:C:T
Brain Putamen basal ganglia	eqtl	3.1e-02	-0.62	5:21900339:G:T
Nerve Tibial	eqtl	3.5e-02	-0.20	5:22765456:T:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
61104	0.6135	113
61105	0.1310	61

Top tissues by expression

showing 100 of 262 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.25	gold quality
middle temporal gyrus	UBERON:0002771	77.10	gold quality
postcentral gyrus	UBERON:0002581	76.00	gold quality
adrenal tissue	UBERON:0018303	75.78	gold quality
cortical plate	UBERON:0005343	75.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	75.02	gold quality
parietal lobe	UBERON:0001872	74.82	gold quality
right uterine tube	UBERON:0001302	74.75	gold quality
primary visual cortex	UBERON:0002436	74.32	gold quality
frontal pole	UBERON:0002795	73.36	gold quality
occipital lobe	UBERON:0002021	73.19	gold quality
Brodmann (1909) area 10	UBERON:0013541	73.06	gold quality
superior frontal gyrus	UBERON:0002661	72.58	gold quality
paraflocculus	UBERON:0005351	72.54	gold quality
middle frontal gyrus	UBERON:0002702	71.95	gold quality
prefrontal cortex	UBERON:0000451	71.89	gold quality
entorhinal cortex	UBERON:0002728	71.34	gold quality
Brodmann (1909) area 46	UBERON:0006483	71.33	gold quality
cerebellar vermis	UBERON:0004720	69.57	silver quality
endometrium epithelium	UBERON:0004811	69.57	gold quality
right adrenal gland	UBERON:0001233	68.70	gold quality
ventricular zone	UBERON:0003053	68.64	gold quality
frontal cortex	UBERON:0001870	68.54	gold quality
right adrenal gland cortex	UBERON:0035827	68.52	gold quality
ganglionic eminence	UBERON:0004023	68.08	gold quality
upper leg skin	UBERON:0004262	67.43	gold quality
adrenal gland	UBERON:0002369	66.96	gold quality
neocortex	UBERON:0001950	66.88	gold quality
left adrenal gland	UBERON:0001234	66.55	gold quality
orbitofrontal cortex	UBERON:0004167	66.49	silver quality
pigmented layer of retina	UBERON:0001782	66.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.66	gold quality
cerebral cortex	UBERON:0000956	65.26	gold quality
adrenal cortex	UBERON:0001235	65.10	gold quality
left adrenal gland cortex	UBERON:0035825	64.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.38	gold quality
pons	UBERON:0000988	64.36	silver quality
nucleus accumbens	UBERON:0001882	63.03	gold quality
telencephalon	UBERON:0001893	62.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.68	gold quality
forebrain	UBERON:0001890	61.62	gold quality
fallopian tube	UBERON:0003889	61.27	gold quality
right frontal lobe	UBERON:0002810	60.71	gold quality
hair follicle	UBERON:0002073	60.58	gold quality
embryo	UBERON:0000922	60.20	gold quality
islet of Langerhans	UBERON:0000006	60.02	gold quality
oviduct epithelium	UBERON:0004804	60.00	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	59.84	gold quality
pituitary gland	UBERON:0000007	59.72	gold quality
brain	UBERON:0000955	59.56	gold quality
central nervous system	UBERON:0001017	59.54	gold quality
spinal cord	UBERON:0002240	58.77	gold quality
cingulate cortex	UBERON:0003027	58.20	gold quality
temporal lobe	UBERON:0001871	57.99	gold quality
anterior cingulate cortex	UBERON:0009835	57.95	gold quality
superior surface of tongue	UBERON:0007371	57.90	gold quality
hypothalamus	UBERON:0001898	57.37	gold quality
Ammon’s horn	UBERON:0001954	56.75	gold quality
corpus callosum	UBERON:0002336	56.35	gold quality
adenohypophysis	UBERON:0002196	55.98	gold quality
caudate nucleus	UBERON:0001873	55.42	gold quality
minor salivary gland	UBERON:0001830	55.22	gold quality
endocervix	UBERON:0000458	54.92	gold quality
buccal mucosa cell	CL:0002336	54.24	silver quality
mouth mucosa	UBERON:0003729	53.26	gold quality
saliva-secreting gland	UBERON:0001044	52.45	gold quality
quadriceps femoris	UBERON:0001377	51.77	gold quality
putamen	UBERON:0001874	51.31	gold quality
bone marrow cell	CL:0002092	50.81	gold quality
vastus lateralis	UBERON:0001379	50.70	gold quality
cranial nerve II	UBERON:0000941	49.75	silver quality
thymus	UBERON:0002370	49.62	gold quality
skin of abdomen	UBERON:0001416	49.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	49.34	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
skin of hip	UBERON:0001554	49.27	silver quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
cerebellum	UBERON:0002037	49.18	gold quality
stromal cell of endometrium	CL:0002255	49.01	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
substantia nigra	UBERON:0002038	48.90	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
calcaneal tendon	UBERON:0003701	48.68	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
epithelial cell of pancreas	CL:0000083	48.47	gold quality
uterine cervix	UBERON:0000002	48.40	gold quality
midbrain	UBERON:0001891	48.33	gold quality
zone of skin	UBERON:0000014	48.29	gold quality
amygdala	UBERON:0001876	48.27	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
cortex of kidney	UBERON:0001225	48.19	gold quality
skin of leg	UBERON:0001511	48.10	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
cerebellar cortex	UBERON:0002129	47.80	gold quality
nasal cavity epithelium	UBERON:0005384	47.70	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	92.01
E-MTAB-7606	no	3.96
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

55 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Cerebral cortex	tissue	25.7
Somatosensory cortex	tissue	25.7
Occipital cortex	tissue	25.2
Temporal cortex	tissue	22.9
Motor cortex	tissue	22.5
Prefrontal cortex	tissue	22.1
Retrosplenial and cingulate cortex	tissue	20.7
Spinal cord	tissue	19.8
Retrosplenial cortex	tissue	19.1
Hippocampal formation	tissue	18.6
Entorhinal cortex	tissue	18.6
Insular cortex	tissue	16.3
Superior colliculi	tissue	13.9
Choroid plexus	tissue	13.4
Thalamus	tissue	13.3
Midbrain	tissue	13.1
Pons	tissue	12.6
Putamen	tissue	12.5
Medulla oblongata	tissue	11.5
Retina	tissue	10.8
Postcentral gyrus	tissue	10.3
Nucleus accumbens	tissue	10.1
Olfactory bulb	tissue	9.3
Corpus callosum	tissue	8.8
Basal ganglia	tissue	8.5
Hypothalamus	tissue	8.2
Ventral forebrain	tissue	8.1
Periaqueductal gray	tissue	7.6
Septum	tissue	7.0
Hippocampus	tissue	6.5
Amygdala	tissue	6.4
Frontal cortex	tissue	5.7
Substantia nigra	tissue	5.6
Cerebellum	tissue	3.3
Locus coeruleus	tissue	2.9
Cervix	tissue	2.8
Fallopian tube	tissue	2.1
Caudate putamen	tissue	2.0
Adrenal gland	tissue	1.6
Pituitary gland	tissue	1.3
Testis	tissue	0.9
Skin 1	tissue	0.7
Breast	tissue	0.4
Urinary bladder	tissue	0.3
Endometrium 1	tissue	0.3
Salivary gland	tissue	0.2
Epididymis	tissue	0.2
Ovary	tissue	0.1
Seminal vesicle	tissue	0.1
Rectum	tissue	0.1
Smooth muscle	tissue	0.1
Tongue	tissue	0.1
Placenta	tissue	0.1
Lung	tissue	0.1
Kidney	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Claustrum (22.4), Ventral spinal cord (19.8), Subiculum (17.1), Posterior insular cortex (16.7), Parieto-insular cortex (15.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CDH12 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 97 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248

Functional genomics

gnomAD constraint: pLI 0.00247, LOEUF 0.668, missense Z 0.946 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000382254 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:21,751,740–21,975,153	791 / 792.8	1.00	no
5:21,975,154–21,975,210	6 / 21.7	0.28	yes (p 7.6e-04)
5:21,975,211–22,078,676	148 / 162.8	0.91	no

Literature-anchored findings (GeneRIF, showing 6)

• E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in non-small-cell lung cancer geneses (PMID:19473719)
• CDH12 may play an important role in the invasion and metastasis of salivary adenoid cystic carcinoma (PMID:21573496)
• CDH12 may influence CRC cell progression. (PMID:26762412)
• Identification of a CDH12 potential candidate genetic variant for an autosomal dominant form of transgrediens and progrediens palmoplantar keratoderma in a Tunisian family. (PMID:31911611)
• An N-Cadherin 2 expressing epithelial cell subpopulation predicts response to surgery, chemotherapy and immunotherapy in bladder cancer. (PMID:34385456)
• The Role of Cadherin 12 (CDH12) in the Peritoneal Fluid among Patients with Endometriosis and Endometriosis-Related Infertility. (PMID:36141853)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdh12	ENSMUSG00000040452
rattus_norvegicus	Cdh12	ENSRNOG00000026392

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), CDH22 (ENSG00000149654), CDH8 (ENSG00000150394), 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:109503) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal coat/ hair morphology	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
Sus scrofa	O02840	86.0%	Diamond
Canis lupus familiaris	F1PAA9	82.9%	Diamond
Danio rerio	Q90275	80.3%	Diamond
Drosophila melanogaster	O15943	74.9%	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
CDH12-AS5	ncRNA	101929617
CDH12-AS4	ncRNA	105374681
CDH12-AS3	ncRNA	105374682
CDH12-AS2	ncRNA	107986345
SNORA105A	snoRNA	106635539
CDH12-AS1	ncRNA	105374683

Protein

Protein identifiers

Cadherin-12 — P55289 (reviewed: P55289)

Alternative names: Brain cadherin, Neural type cadherin 2

All UniProt accessions (1): P55289

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.

Subcellular location. Cell membrane.

Tissue specificity. Brain.

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 (2)

UniProt ID	Names	Canonical?
P55289-1	1	yes
P55289-2	2

RefSeq proteins (9): NP_001304156, NP_001304157, NP_001351033, NP_001351034, NP_001351035, NP_001351036, NP_001351037, NP_001351038, NP_004052* (*=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 (25 total): domain 5, sequence conflict 5, glycosylation site 4, sequence variant 3, topological domain 2, signal peptide 1, propeptide 1, modified residue 1, splice variant 1, chain 1, transmembrane region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55289-F1	77.19	0.47

Human Protein Atlas

Protein class: Predicted membrane proteins, Plasma proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH uncertain · IF uncertain

Functional residue map

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

Post-translational modifications (1)

Type	Positions
Phosphoserine	787

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	256, 456, 537, 545

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-418990	Adherens junctions interactions	curated
R-HSA-446728	Cell junction organization	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-421270	Cell-cell junction organization	—

MSigDB gene sets: 100 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_CALCIUM_DEPENDENT_CELL_CELL_ADHESION, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION, MCLACHLAN_DENTAL_CARIES_DN, HOOI_ST7_TARGETS_DN, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_ADHERENS_JUNCTION_ORGANIZATION, GOBP_CELL_CELL_JUNCTION_ASSEMBLY, GOCC_CELL_CELL_JUNCTION, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_ANCHORING_JUNCTION

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

Reactome top-level categories

3 top-level categories:

Category	Pathways
Cell-cell junction organization	1
Cell junction organization	1
Cell-Cell communication	1

GO top-level categories

17 GO namespaces:

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
membrane	1
cell periphery	1
cell-cell junction	1
extrinsic component of plasma membrane	1
plasma membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 15 of 612 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH12	LRRIQ3	A6PVS8	386
CDH12	DRC4	O95995	370
CDH12	ABCB10	Q9NRK6	370
CDH12	TDG	Q13569	370
CDH12	BRINP3	Q76B58	369
CDH12	CRACD	Q6ZU35	365
CDH12	ABCB8	Q9NUT2	363
CDH12	KIRREL3	Q8IZU9	362
CDH12	KLK2	P20151	358
CDH12	WFIKKN1	Q96NZ8	356
CDH12	RNF157	Q96PX1	353
CDH12	ZNF804B	A4D1E1	346
CDH12	CDH17	Q12864	340
CDH12	DCHS1	Q96JQ0	332
CDH12	CDADC1	Q9BWV3	321

IntAct

Human interaction partners of CDH12 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
ARVCF	association	0.350	2

BioGRID (17 interactions; top human partners by supporting records): CTNNA3 (Affinity Capture-MS; 2 records), ARVCF (Affinity Capture-MS), CDC20B (Affinity Capture-MS), CDH24 (Affinity Capture-MS), CDH8 (Affinity Capture-MS), CHEK2 (Affinity Capture-MS), CTNNA1 (Affinity Capture-MS), CTNNA2 (Affinity Capture-MS), CTNNB1 (Affinity Capture-MS), FRMD4A (Affinity Capture-MS), PCDH1 (Affinity Capture-MS), PKP4 (Affinity Capture-MS), PSEN1 (Affinity Capture-MS), RBM14-RBM4 (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
calcium(2+)	“up-regulates activity”	CDH12	“chemical activation”
CDH12	“up-regulates activity”	CTNNB1	binding

Disease & clinical

Genetic variants

Variant evidence for CDH12: 167 ClinVar records (1 pathogenic / likely pathogenic); 11 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	127
Likely benign	15
Benign	11

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1809200	GRCh37/hg19 5p15.33-14.1(chr5:113577-26164852)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CDH12’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

AlphaMissense

1,909 missense substitutions predicted likely pathogenic (of 5,230 scored), across 470 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
D152	8	0.998	1.000
D186	8	0.997	0.999
D188	8	0.997	0.999
D155	8	0.996	1.000
D241	8	0.996	0.999
D297	8	0.994	0.997
F102	8	0.993	1.000
D295	8	0.991	0.996
D261	8	0.988	0.998
D264	8	0.988	0.999
N154	8	0.987	0.999
F209	8	0.985	0.999
D516	8	0.984	0.995
D669	8	0.981	0.993
F160	8	0.976	0.999
F269	8	0.974	0.999
D514	8	0.974	0.990
D226	8	0.971	0.996
F317	8	0.969	0.998
F384	8	0.968	0.997

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Chromophobe)

Disease associations

OMIM: gene MIM:600562 | disease phenotypes:

GWAS associations

11 associations:

Study	Trait	p-value
GCST008810_38	Smoking initiation (ever regular vs never regular)	1e-8
GCST004568_1	Body mass index (physical activity interaction)	3e-8
GCST007603_35	Smoking initiation	5e-8
GCST005578_5	Low white blood cell count (conditioned on rs2814778)	2e-7
GCST004568_2	Body mass index (physical activity interaction)	3e-7
GCST005578_4	Low white blood cell count (conditioned on rs2814778)	4e-7
GCST005760_6	Dimensional psychopathology (Cognitive)	4e-7
GCST007678_2	Brooding (response to stress)	5e-7
GCST004558_118	Body mass index (joint analysis main effects and physical activity interaction)	7e-7
GCST000427_5	Waist circumference	2e-6
GCST004863_33	Mosquito bite size	9e-6

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008002	physical activity measurement
EFO:0003940	physical activity
EFO:0008378	mosquito bite reaction size measurement
EFO:0009098	cognitive domain measurement
EFO:0005670	smoking initiation
EFO:0009858	brooding stress response

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation, affects expression, decreases expression	4
sodium arsenite	decreases methylation, affects methylation, decreases expression, increases reaction	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Copper	affects cotreatment, decreases expression, affects binding	2
Valproic Acid	decreases expression	2
methyleugenol	decreases expression	1
bisphenol A	affects methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
glycidamide	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Coumestrol	affects cotreatment, increases expression	1
Lead	affects methylation	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Niclosamide	decreases reaction, increases expression	1
Silicon Dioxide	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Cyclosporine	decreases expression	1
Silver Compounds	increases expression	1
Cadmium Chloride	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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