CDH18

Summary

CDH18 (cadherin 18, HGNC:1757) is a protein-coding gene on chromosome 5p14.3, encoding Cadherin-18 (Q13634). Cadherins are calcium-dependent cell adhesion proteins.

This gene encodes a type II classical cadherin from the cadherin superfamily of integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins 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 HAV cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is expressed specifically in the central nervous system and is putatively involved in synaptic adhesion, axon outgrowth and guidance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1016 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 150 total
• MANE Select transcript: NM_004934

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1757
Approved symbol	CDH18
Name	cadherin 18
Location	5p14.3
Locus type	gene with protein product
Status	Approved
Aliases	CDH14, EY-CADHERIN
Ensembl gene	ENSG00000145526
Ensembl biotype	protein_coding
OMIM	603019
Entrez	1016

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000274170, ENST00000382275, ENST00000502796, ENST00000503132, ENST00000506372, ENST00000507632, ENST00000507958, ENST00000508350, ENST00000510297, ENST00000511273, ENST00000511423, ENST00000515257, ENST00000871941, ENST00000959452, ENST00000959453

RefSeq mRNA: 11 — MANE Select: NM_004934 NM_001167667, NM_001291956, NM_001291957, NM_001349556, NM_001349558, NM_001349559, NM_001349560, NM_001349561, NM_001349562, NM_001349563, NM_004934

CCDS: CCDS3889, CCDS54835, CCDS75229

Canonical transcript exons

ENST00000382275 — 13 exons

Exon	Start	End
ENSE00001021722	19571579	19571832
ENSE00001021725	19520657	19520778
ENSE00001021726	19483301	19483552
ENSE00001021728	19543869	19544005
ENSE00001021729	19502992	19503109
ENSE00001021733	19591057	19591244
ENSE00001136559	19612434	19612601
ENSE00001491526	19471296	19473716
ENSE00001491537	19838759	19839242
ENSE00001491539	19981060	19981178
ENSE00001491542	19988086	19988200
ENSE00001602150	19721347	19721466
ENSE00003687797	19746942	19747236

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 95.83.

FANTOM5 (CAGE): breadth broad, TPM avg 5.7530 / max 1180.2863, expressed in 421 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61085	2.4640	293
61102	0.8157	154
61098	0.5474	108
61097	0.5109	104
61095	0.3918	90
61101	0.3123	99
61086	0.2521	92
61094	0.1685	55
61093	0.0919	22
61092	0.0620	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	95.83	gold quality
cerebellar vermis	UBERON:0004720	95.20	gold quality
paraflocculus	UBERON:0005351	93.16	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.63	gold quality
cerebellum	UBERON:0002037	90.77	gold quality
frontal pole	UBERON:0002795	90.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.52	gold quality
orbitofrontal cortex	UBERON:0004167	90.32	gold quality
cerebellar cortex	UBERON:0002129	90.20	gold quality
cerebellar hemisphere	UBERON:0002245	90.04	gold quality
Brodmann (1909) area 10	UBERON:0013541	89.97	gold quality
superior frontal gyrus	UBERON:0002661	89.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.16	gold quality
postcentral gyrus	UBERON:0002581	87.62	gold quality
parietal lobe	UBERON:0001872	87.56	gold quality
entorhinal cortex	UBERON:0002728	86.33	gold quality
prefrontal cortex	UBERON:0000451	86.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.00	gold quality
primary visual cortex	UBERON:0002436	85.91	gold quality
frontal lobe	UBERON:0016525	85.64	gold quality
frontal cortex	UBERON:0001870	85.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.12	gold quality
occipital lobe	UBERON:0002021	84.92	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.76	gold quality
sperm	CL:0000019	84.46	gold quality
lateral nuclear group of thalamus	UBERON:0002736	84.00	gold quality
neocortex	UBERON:0001950	83.96	gold quality
pons	UBERON:0000988	83.90	gold quality
superior vestibular nucleus	UBERON:0007227	83.76	gold quality
right frontal lobe	UBERON:0002810	83.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	18095.30
E-HCAD-25	yes	83.40
E-ANND-3	yes	5.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting CDH18, 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-3692-3P	99.98	70.27	2139
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-3130-5P	98.14	66.00	711
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-1912-5P	97.94	67.98	832
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-4482-5P	97.53	65.68	598
HSA-MIR-616-3P	96.82	66.99	784
HSA-MIR-4436B-5P	96.71	68.37	1346

Literature-anchored findings (GeneRIF, showing 5)

• Azoospermic testis showed down-regulation of CDH18 and PCDH17. (PMID:20180417)
• A role for PDLIM7 and CDH18, regulating MDM2 protein in CDK4/6 inhibitor-treated cells. (PMID:29789718)
• CDH18 overexpression significantly inhibited the invasion and migration ability but not proliferation ability in glioma cell lines. (PMID:30078018)
• Effect of COP1 in Promoting the Tumorigenesis of Gastric Cancer by Down-Regulation of CDH18 via PI3K/AKT Signal Pathway. (PMID:37025097)
• A duodenal mucosa transcriptome study identified reduced expression of a novel gene CDH18 in celiac disease. (PMID:37813809)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdh18a	ENSDARG00000061371
danio_rerio	CDH18	ENSDARG00000102769
mus_musculus	Cdh18	ENSMUSG00000040420
rattus_norvegicus	Cdh18	ENSRNOG00000010535

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), 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-18 — Q13634 (reviewed: Q13634)

Alternative names: Cadherin-14

All UniProt accessions (4): D6RER2, D6RIH8, Q13634, H0YAK3

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.

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?
Q13634-1	1	yes
Q13634-2	2

RefSeq proteins (11): NP_001161139, NP_001278885, NP_001278886, NP_001336485, NP_001336487, NP_001336488, NP_001336489, NP_001336490, NP_001336491, NP_001336492, NP_004925* (*=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 (21 total): domain 5, glycosylation site 4, sequence conflict 4, topological domain 2, signal peptide 1, propeptide 1, modified residue 1, splice variant 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13634-F1	77.57	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.

Post-translational modifications (1): 786

Glycosylation sites (4): 36, 255, 455, 536

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

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

MSigDB gene sets: 90 (showing top): XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_CALCIUM_DEPENDENT_CELL_CELL_ADHESION, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, MODULE_66, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION, ONDER_CDH1_TARGETS_2_UP, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_ADHERENS_JUNCTION_ORGANIZATION, GOBP_CELL_CELL_JUNCTION_ASSEMBLY, GOCC_CELL_CELL_JUNCTION, SHEN_SMARCA2_TARGETS_DN, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_ANCHORING_JUNCTION, GOCC_EXTRINSIC_COMPONENT_OF_MEMBRANE

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

Rollup of top-3 pathways:

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

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
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

880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH18	BASP1	P80723	702
CDH18	CTNNB1	P35222	522
CDH18	TAF11	Q15544	462
CDH18	ARID1A	O14497	458
CDH18	SH3BP5L	Q7L8J4	454
CDH18	KNDC1	Q76NI1	446
CDH18	PKD1	P98161	438
CDH18	CDH15	P55291	436
CDH18	CDH19	Q9H159	425
CDH18	CDH10	Q9Y6N8	424
CDH18	CDH6	P55285	424
CDH18	CDH2	P19022	424
CDH18	HDAC4	P56524	423
CDH18	CDH9	Q9ULB4	421
CDH18	CDH12	P55289	415

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MYOG	CDH18	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (7): CDH18 (Affinity Capture-Western), CDH18 (Co-localization), CDH18 (Co-localization), CDH18 (Affinity Capture-MS), CDH18 (Protein-peptide), CDH18 (Affinity Capture-RNA), MYOG (Two-hybrid)

ESM2 similar proteins: A0A8M2BIB6, F1QSQ0, F8W3X3, H2EQR6, O35902, O54800, O55111, O93319, P32926, P33545, P55280, P55285, P55286, P55287, P55288, P55289, P55292, P55849, P55850, P70407, P70408, P79995, P97291, P97326, Q01107, Q02413, Q02487, Q08554, Q08DJ5, Q13634, Q14126, Q14574, Q28060, Q3SWX5, Q5DWV1, Q5RJH3, Q61495, Q68SP4, Q6W3B0, Q7TMD7

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

2 interactions.

A	Effect	B	Mechanism
calcium(2+)	“up-regulates activity”	CDH18	“chemical activation”
CDH18	“up-regulates activity”	CTNNB1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	125
Likely benign	13
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4306 predictions. Top by Δscore:

Variant	Effect	Δscore
5:19473712:AATTG:A	acceptor_gain	1.0000
5:19473713:ATTG:A	acceptor_gain	1.0000
5:19473714:TTG:T	acceptor_gain	1.0000
5:19473715:TG:T	acceptor_gain	1.0000
5:19473716:GC:G	acceptor_loss	1.0000
5:19473717:C:CC	acceptor_gain	1.0000
5:19473717:CTGA:C	acceptor_loss	1.0000
5:19519487:ATAC:A	donor_gain	1.0000
5:19520651:ACTT:A	donor_loss	1.0000
5:19520652:CTTA:C	donor_loss	1.0000
5:19520653:TTAC:T	donor_loss	1.0000
5:19520654:TAC:T	donor_loss	1.0000
5:19520655:A:AC	donor_gain	1.0000
5:19520655:A:T	donor_loss	1.0000
5:19520656:C:A	donor_loss	1.0000
5:19520656:C:CC	donor_gain	1.0000
5:19520656:CCTGG:C	donor_gain	1.0000
5:19520775:TTAT:T	acceptor_gain	1.0000
5:19520775:TTATC:T	acceptor_loss	1.0000
5:19520776:TAT:T	acceptor_gain	1.0000
5:19520778:TC:T	acceptor_loss	1.0000
5:19520779:C:CA	acceptor_loss	1.0000
5:19520779:C:CC	acceptor_gain	1.0000
5:19520780:T:A	acceptor_loss	1.0000
5:19543847:TGTGA:T	donor_gain	1.0000
5:19544001:AGTAT:A	acceptor_gain	1.0000
5:19544002:GTAT:G	acceptor_gain	1.0000
5:19544003:TAT:T	acceptor_gain	1.0000
5:19544004:AT:A	acceptor_gain	1.0000
5:19544004:ATC:A	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003094 (5:20318340 C>T), RS1000006536 (5:20219544 C>A,G), RS1000012778 (5:20442904 C>T), RS1000015203 (5:20134381 C>G), RS1000017440 (5:20155933 A>G,T), RS1000021816 (5:19970657 C>T), RS1000022951 (5:19677776 T>C), RS1000023290 (5:20322646 T>G), RS1000031033 (5:20537667 A>G), RS1000034427 (5:19929978 G>C,T), RS1000037060 (5:19479548 C>T), RS1000039595 (5:19636429 T>C), RS1000041081 (5:19516295 T>A), RS1000041834 (5:19597210 C>T), RS1000042926 (5:20408715 A>T)

Disease associations

OMIM: gene MIM:603019 | disease phenotypes: MIM:602081

GenCC curated gene-disease

Mondo (1): childhood apraxia of speech (MONDO:0011184)

Orphanet (1): Isolated childhood apraxia of speech (Orphanet:209908)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000779_4	Depression (quantitative trait)	2.000000e-06
GCST002616_20	Mitochondrial DNA levels	5.000000e-06
GCST002900_3	Obesity in adult survivors of childhood cancer exposed to cranial radiation	1.000000e-07
GCST003329_12	Response to anti-TNF therapy in rheumatoid arthritis	6.000000e-06
GCST004227_10	Obstetric antiphospholipid syndrome	6.000000e-06
GCST005648_40	Serum metabolite concentrations in chronic kidney disease	1.000000e-08
GCST006956_18	Erectile dysfunction	9.000000e-06
GCST007690_1	Metabolic coherence (transcriptomic)	2.000000e-07
GCST008114_36	Type 2 diabetes	4.000000e-06
GCST008448_1	Diabetes (gestational)	7.000000e-06
GCST009100_2	Resistant hypertension	5.000000e-07
GCST90002409_31	Childhood body mass index	4.000000e-07

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006312	mitochondrial DNA measurement
EFO:0004653	response to TNF antagonist
EFO:0009864	metabolic network measurement
EFO:0009865	transcriptome measurement
EFO:1002006	treatment-resistant hypertension
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
bisphenol A	affects expression, affects methylation, affects cotreatment, decreases methylation	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Ethinyl Estradiol	decreases expression, affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
methylmercuric chloride	increases expression	1
trichostatin A	increases expression	1
benzo(e)pyrene	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
belinostat	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	increases expression	1
Lead	affects expression	1
Methapyrilene	decreases methylation	1
Polychlorinated Biphenyls	affects expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Vanadates	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05185583	PHASE2	COMPLETED	Methylphenidate in Childhood Apraxia of Speech
NCT07216001	PHASE2	NOT_YET_RECRUITING	Role of Omega-DEK in Childhood Apraxia of Speech
NCT03903120	PHASE1	COMPLETED	ASSIST: Treatment for Childhood Apraxia of Speech
NCT01097161	Not specified	COMPLETED	Stuttering and Apraxia of Speech: the Efficacy of an Intervention Program
NCT02022410	Not specified	COMPLETED	CAS and Length of Hospital Stay After TKA
NCT03238677	Not specified	COMPLETED	Treating Childhood Apraxia of Speech
NCT03700151	Not specified	UNKNOWN	Efficacy of an Intervention for the Children With Severe Speech Sounds Disorders
NCT04642053	Not specified	RECRUITING	A Randomized Control Trial of Motor-based Intervention for CAS
NCT04825145	Not specified	COMPLETED	Preeclampsia and Contact Activation
NCT04832503	Not specified	COMPLETED	Childhood Apraxia of Speech: Experience Dependent Changes Induced by Treatment
NCT05066178	Not specified	RECRUITING	Speech Treatment for Minimally Verbal Children With ASD and CAS
NCT05675306	Not specified	ACTIVE_NOT_RECRUITING	Dose Frequency RCT on DTTC in Children With CAS
NCT05916222	Not specified	RECRUITING	The Effects of Caregiver Training on DTTC Treatment Outcomes in CAS
NCT06385470	Not specified	UNKNOWN	Treatment of Cantonese Speakers With Childhood Apraxia of Speech
NCT07087249	Not specified	NOT_YET_RECRUITING	Efficacy of Ultrasound Biofeedback in Brazilian Childhood Apraxia of Speech
NCT07526246	Not specified	NOT_YET_RECRUITING	Motor-based Intervention for Childhood Apraxia of Speech: DTTC-Connect