CDH9

Summary

CDH9 (cadherin 9, HGNC:1768) is a protein-coding gene on chromosome 5p14.1, encoding Cadherin-9 (Q9ULB4). Cadherins are calcium-dependent cell adhesion proteins.

This gene encodes a type II classical cadherin from the cadherin superfamily, 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. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein’s homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins.

Source: NCBI Gene 1007 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 105 total — 2 pathogenic
• MANE Select transcript: NM_016279

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1768
Approved symbol	CDH9
Name	cadherin 9
Location	5p14.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113100
Ensembl biotype	protein_coding
OMIM	609974
Entrez	1007

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000231021, ENST00000505020, ENST00000505045, ENST00000511822, ENST00000513289

RefSeq mRNA: 1 — MANE Select: NM_016279 NM_016279

CCDS: CCDS3893

Canonical transcript exons

ENST00000231021 — 12 exons

Exon	Start	End
ENSE00000804464	26890428	26890564
ENSE00000908825	26903637	26903824
ENSE00000908826	26902476	26902729
ENSE00001156298	26880597	26881623
ENSE00002071430	27038463	27038586
ENSE00003463474	26889836	26889957
ENSE00003508097	26885614	26885865
ENSE00003533128	26906719	26906838
ENSE00003564063	26988106	26988382
ENSE00003569244	26915630	26915924
ENSE00003654945	26885966	26886083
ENSE00003692569	26905959	26906126

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 82.55.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.1787 / max 947.3385, expressed in 158 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61134	1.7356	137
61135	0.3269	89
61133	0.1162	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	82.55	gold quality
prefrontal cortex	UBERON:0000451	78.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.91	gold quality
anterior cingulate cortex	UBERON:0009835	76.59	gold quality
cingulate cortex	UBERON:0003027	76.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.40	gold quality
right frontal lobe	UBERON:0002810	76.33	gold quality
frontal cortex	UBERON:0001870	74.22	gold quality
nucleus accumbens	UBERON:0001882	74.08	gold quality
neocortex	UBERON:0001950	73.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	73.18	gold quality
cerebral cortex	UBERON:0000956	71.71	gold quality
middle temporal gyrus	UBERON:0002771	71.70	gold quality
telencephalon	UBERON:0001893	70.08	gold quality
primary visual cortex	UBERON:0002436	70.00	gold quality
amygdala	UBERON:0001876	69.47	gold quality
caudate nucleus	UBERON:0001873	68.07	gold quality
putamen	UBERON:0001874	66.89	gold quality
forebrain	UBERON:0001890	65.82	gold quality
temporal lobe	UBERON:0001871	65.37	gold quality
Ammon’s horn	UBERON:0001954	64.99	gold quality
occipital lobe	UBERON:0002021	63.97	gold quality
superior frontal gyrus	UBERON:0002661	63.51	gold quality
hypothalamus	UBERON:0001898	62.17	gold quality
adult mammalian kidney	UBERON:0000082	61.65	gold quality
brain	UBERON:0000955	60.72	gold quality
entorhinal cortex	UBERON:0002728	58.85	silver quality
corpus callosum	UBERON:0002336	58.78	gold quality
mucosa of urinary bladder	UBERON:0001259	57.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	99.76
E-ANND-3	no	4.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting CDH9, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-12132	99.47	68.90	1341

Literature-anchored findings (GeneRIF, showing 3)

• Cadherin-9 is a reliable cell surface marker for fibroblasts in healthy and diseased kidneys. (PMID:17668045)
• The CC genotype of rs4307059 located in the region between CDH9 and CDH10 is associated with completed suicide in a Polish cohort (PMID:22846907)
• MiR-130b-3p promotes colorectal cancer progression by targeting CHD9. (PMID:35100082)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdh9	ENSMUSG00000025370
rattus_norvegicus	Cdh9	ENSRNOG00000033837

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), CDH6 (ENSG00000113361), CDH26 (ENSG00000124215), 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-9 — Q9ULB4 (reviewed: Q9ULB4)

All UniProt accessions (3): D6RBT9, E7EPN0, Q9ULB4

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.

RefSeq proteins (1): NP_057363* (*=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 (19 total): domain 5, glycosylation site 4, sequence variant 2, topological domain 2, signal peptide 1, propeptide 1, modified residue 1, sequence conflict 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULB4-F1	77.60	0.47

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): 255, 437, 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: 117 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, CHX10_01, GOBP_CALCIUM_DEPENDENT_CELL_CELL_ADHESION, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, EVI1_05, GOBP_CELL_CELL_ADHESION, GTGCCTT_MIR506, GOBP_CELL_JUNCTION_ORGANIZATION, AACTTT_UNKNOWN, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_ADHERENS_JUNCTION_ORGANIZATION, FOXJ2_02, GOBP_CELL_CELL_JUNCTION_ASSEMBLY, GOCC_CELL_CELL_JUNCTION, CTTTGTA_MIR524

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), cell-cell adhesion mediated by cadherin (GO:0044331), cell-cell adhesion (GO:0098609), synaptic membrane adhesion (GO:0099560), cell adhesion (GO:0007155)

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	4
cell-cell junction organization	2
anatomical structure morphogenesis	1
cell junction assembly	1
cell motility	1
cell adhesion	1
synapse organization	1
cellular process	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

1168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH9	TAS2R1	Q9NYW7	804
CDH9	SEMA5A	Q13591	787
CDH9	NLGN4X	Q8N0W4	762
CDH9	CNTN4	Q8IWV2	732
CDH9	NLGN3	Q9NZ94	730
CDH9	FBXO40	Q9UH90	691
CDH9	NLGN1	Q8N2Q7	687
CDH9	NRXN1	Q9ULB1	680
CDH9	ASTN2	O75129	676
CDH9	COP1	Q8NHY2	630
CDH9	PTCHD1	Q96NR3	593
CDH9	SHANK3	Q9BYB0	584
CDH9	SHANK2	Q9UPX8	567
CDH9	DLGAP2	Q9P1A6	563
CDH9	ATP1A2	P50993	553

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CDH9	MEOX2	psi-mi:“MI:0915”(physical association)	0.370
CTNNB1	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): CDH9 (Affinity Capture-MS), CDH9 (Affinity Capture-MS), CDH9 (Affinity Capture-Western), CDH9 (Positive Genetic), CDH9 (Affinity Capture-MS), CDH9 (Protein-peptide), CDH9 (Affinity Capture-RNA), MEOX2 (Two-hybrid)

ESM2 similar proteins: A0A1S4GGP7, B1Q236, B8V7Q1, B8VIW9, F1QSQ0, F8W3X3, G5EDK5, H2A0L8, O02466, O15943, O44386, O44730, P28827, P34616, P35822, P55289, P70408, Q02763, Q02858, Q03600, Q03763, Q06807, Q09165, Q15262, Q19319, Q24247, Q24298, Q5RJH3, Q60ZN5, Q61495, Q68SP4, Q6W3B0, Q7TMD7, Q7TSF0, Q7TSF1, Q86SJ6, Q86WI1, Q8JHW2, Q8VHN7, Q8WXG9

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”	CDH9	“chemical activation”
CDH9	“up-regulates activity”	CTNNB1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	92
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
144287	GRCh38/hg38 5p14.1(chr5:25801575-27125347)x3	Pathogenic
393852	GRCh37/hg19 5p15.33-13.3(chr5:3159498-30585683)x3	Pathogenic

SpliceAI

2688 predictions. Top by Δscore:

Variant	Effect	Δscore
5:26881619:TAAAA:T	acceptor_gain	1.0000
5:26881620:AAAA:A	acceptor_gain	1.0000
5:26881624:C:CC	acceptor_gain	1.0000
5:26884140:T:A	donor_gain	1.0000
5:26885880:A:C	acceptor_gain	1.0000
5:26886084:C:CC	acceptor_gain	1.0000
5:26889831:TTTAC:T	donor_loss	1.0000
5:26889832:TTAC:T	donor_loss	1.0000
5:26889833:TACCT:T	donor_loss	1.0000
5:26889834:A:AG	donor_loss	1.0000
5:26889835:C:CT	donor_loss	1.0000
5:26890108:C:CT	acceptor_gain	1.0000
5:26902472:TTACT:T	donor_loss	1.0000
5:26902473:TA:T	donor_loss	1.0000
5:26902474:A:AC	donor_gain	1.0000
5:26902474:AC:A	donor_loss	1.0000
5:26902475:C:A	donor_loss	1.0000
5:26902475:C:CA	donor_gain	1.0000
5:26902475:CT:C	donor_gain	1.0000
5:26902475:CTT:C	donor_gain	1.0000
5:26902475:CTTT:C	donor_gain	1.0000
5:26902475:CTTTA:C	donor_gain	1.0000
5:26902728:TT:T	acceptor_gain	1.0000
5:26902730:C:CC	acceptor_gain	1.0000
5:26903652:AATC:A	donor_gain	1.0000
5:26903655:C:A	donor_gain	1.0000
5:26903659:T:TA	donor_gain	1.0000
5:26903660:C:A	donor_gain	1.0000
5:26903667:AT:A	donor_gain	1.0000
5:26903668:T:TA	donor_gain	1.0000

AlphaMissense

5276 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:26906063:A:T	I236K	1.000
5:26906739:A:G	F208S	1.000
5:26906829:A:T	V178D	1.000
5:26915692:T:G	D154A	1.000
5:26915719:A:G	F145S	1.000
5:26915776:A:G	L126P	1.000
5:26915830:C:T	G108E	1.000
5:26915851:A:G	F101S	1.000
5:26915885:A:C	Y90D	1.000
5:26881490:A:C	F672L	0.999
5:26881490:A:T	F672L	0.999
5:26881492:A:G	F672L	0.999
5:26881503:T:A	D668V	0.999
5:26881503:T:G	D668A	0.999
5:26881504:C:G	D668H	0.999
5:26906051:T:G	D240A	0.999
5:26906052:C:G	D240H	0.999
5:26906057:G:T	A238D	0.999
5:26906058:C:G	A238P	0.999
5:26906063:A:C	I236R	0.999
5:26906120:A:C	I217R	0.999
5:26906120:A:T	I217K	0.999
5:26906739:A:C	F208C	0.999
5:26906767:A:C	Y199D	0.999
5:26906802:T:A	D187V	0.999
5:26906802:T:C	D187G	0.999
5:26906802:T:G	D187A	0.999
5:26906803:C:G	D187H	0.999
5:26906808:T:G	D185A	0.999
5:26906809:C:G	D185H	0.999

dbSNP variants (sampled 300 via entrez): RS1000009062 (5:27036028 T>A,G), RS1000024331 (5:26930547 C>A,T), RS1000025636 (5:26916771 G>C,T), RS1000090460 (5:26883215 T>A,G), RS1000102756 (5:26973205 C>T), RS1000106393 (5:27002178 A>C), RS1000130934 (5:26898492 C>G,T), RS1000136289 (5:26955199 C>A,G), RS1000144788 (5:26889628 C>A), RS1000163049 (5:26964622 A>G,T), RS1000188464 (5:26927730 A>G), RS1000191237 (5:26898566 G>T), RS1000224166 (5:27018962 C>T), RS1000254417 (5:27008519 C>A,G), RS1000255964 (5:26895472 A>C)

Disease associations

OMIM: gene MIM:609974 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000382_1	Autism	2.000000e-10
GCST000873_8	Anorexia nervosa	8.000000e-06
GCST001525_29	Visceral fat	3.000000e-06
GCST001629_1	Response to platinum-based chemotherapy in non-small-cell lung cancer	2.000000e-06
GCST001629_4	Response to platinum-based chemotherapy in non-small-cell lung cancer	3.000000e-06
GCST001800_8	β2-Glycoprotein I (β2-GPI) plasma levels	2.000000e-06
GCST002097_11	Coronary artery calcification	8.000000e-06
GCST003081_7	Glucocorticoid-induced osteonecrosis (age 10 years and older)	4.000000e-06
GCST003225_25	Pelvic organ prolapse (moderate/severe)	2.000000e-07
GCST004069_2	Cerebrospinal fluid AB1-42 levels	1.000000e-06
GCST007324_104	Adventurousness	1.000000e-08
GCST007325_95	General risk tolerance (MTAG)	1.000000e-10
GCST007627_1	Impulsivity (attentional)	9.000000e-07
GCST007637_29	Diffusing capacity of carbon monoxide	3.000000e-07
GCST008295_25	Number of decayed, missing and filled tooth surfaces or use of dentures	3.000000e-08
GCST008306_40	Dentures	9.000000e-08
GCST010572_2	Sweet taste preference	5.000000e-06
GCST90011898_129	Alanine aminotransferase levels	6.000000e-25
GCST90011899_46	Aspartate aminotransferase levels	1.000000e-14

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004555	glycoprotein measurement
EFO:0004723	coronary artery calcification
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0008579	risk-taking behaviour
EFO:0006946	behavioural disinhibition measurement
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0010078	dentures
EFO:0010156	sweet liking measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression	3
trichostatin A	affects cotreatment, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	decreases expression, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases methylation	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment, increases expression	1
perfluorobutanesulfonic acid	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Ethanol	affects cotreatment, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Fluorocarbons	affects cotreatment, decreases expression	1
Folic Acid	affects cotreatment, increases expression	1
Hydrocarbons, Chlorinated	affects cotreatment, decreases expression	1
Metals	decreases expression, affects cotreatment	1
Pentachlorophenol	affects cotreatment, decreases expression	1
Polychlorinated Biphenyls	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Teratogens	decreases expression	1

Clinical trials (associated diseases)

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