CDH16

Summary

CDH16 (cadherin 16, HGNC:1755) is a protein-coding gene on chromosome 16q22.1, encoding Cadherin-16 (O75309). Cadherins are calcium-dependent cell adhesion proteins.

This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. Mapped to a previously identified cluster of cadherin genes on chromosome 16q22.1, the gene localizes with superfamily members CDH1, CDH3, CDH5, CDH8 and CDH11. The protein consists of an extracellular domain containing 6 cadherin domains, a transmembrane region and a truncated cytoplasmic domain but lacks the prosequence and tripeptide HAV adhesion recognition sequence typical of most classical cadherins. Expression is exclusively in kidney, where the protein functions as the principal mediator of homotypic cellular recognition, playing a role in the morphogenic direction of tissue development. Alternatively spliced transcript variants encoding distinct isoforms have been identified.

Source: NCBI Gene 1014 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 164 total
• MANE Select transcript: NM_004062

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1755
Approved symbol	CDH16
Name	cadherin 16
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166589
Ensembl biotype	protein_coding
OMIM	603118
Entrez	1014

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 30 protein_coding, 2 nonsense_mediated_decay

ENST00000299752, ENST00000394055, ENST00000565235, ENST00000565796, ENST00000567009, ENST00000567269, ENST00000568632, ENST00000568698, ENST00000570262, ENST00000867160, ENST00000867161, ENST00000867162, ENST00000867163, ENST00000867164, ENST00000867165, ENST00000867166, ENST00000867167, ENST00000867168, ENST00000867169, ENST00000867170, ENST00000867171, ENST00000867172, ENST00000867173, ENST00000867174, ENST00000867175, ENST00000867176, ENST00000867177, ENST00000867178, ENST00000867179, ENST00000867180, ENST00000867181, ENST00000951240

RefSeq mRNA: 4 — MANE Select: NM_004062 NM_001204744, NM_001204745, NM_001204746, NM_004062

CCDS: CCDS10823, CCDS56002, CCDS58471, CCDS58472

Canonical transcript exons

ENST00000299752 — 18 exons

Exon	Start	End
ENSE00001104515	66918021	66918078
ENSE00001104525	66914216	66914412
ENSE00001104540	66916065	66916203
ENSE00001300836	66908122	66908489
ENSE00001862095	66918804	66918885
ENSE00003466084	66917642	66917725
ENSE00003488107	66912242	66912430
ENSE00003505042	66911182	66911315
ENSE00003509764	66909267	66909383
ENSE00003516092	66909986	66910093
ENSE00003597139	66913491	66913613
ENSE00003603638	66912504	66912580
ENSE00003622258	66910260	66910502
ENSE00003637674	66912664	66912891
ENSE00003677633	66913131	66913281
ENSE00003685757	66916274	66916429
ENSE00003690817	66911899	66912140
ENSE00003791552	66915220	66915378

Expression profiles

Bgee: expression breadth ubiquitous, 114 present calls, max score 99.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8622 / max 495.2301, expressed in 45 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157726	0.4813	32
157727	0.3809	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	99.38	gold quality
adult mammalian kidney	UBERON:0000082	99.24	gold quality
renal medulla	UBERON:0000362	98.93	gold quality
kidney	UBERON:0002113	95.16	gold quality
nephron tubule	UBERON:0001231	92.04	gold quality
cortex of kidney	UBERON:0001225	91.08	gold quality
kidney epithelium	UBERON:0004819	90.06	gold quality
lower esophagus mucosa	UBERON:0035834	89.72	gold quality
adult organism	UBERON:0007023	89.40	gold quality
left lobe of thyroid gland	UBERON:0001120	88.64	gold quality
thyroid gland	UBERON:0002046	88.44	gold quality
right lobe of thyroid gland	UBERON:0001119	87.40	gold quality
metanephros	UBERON:0000081	86.92	gold quality
renal glomerulus	UBERON:0000074	85.83	gold quality
metanephric glomerulus	UBERON:0004736	85.50	gold quality
esophagus mucosa	UBERON:0002469	71.51	gold quality
endometrium epithelium	UBERON:0004811	67.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	61.51	gold quality
caput epididymis	UBERON:0004358	58.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	57.82	gold quality
right uterine tube	UBERON:0001302	57.39	gold quality
colonic epithelium	UBERON:0000397	56.19	silver quality
oocyte	CL:0000023	55.67	gold quality
fallopian tube	UBERON:0003889	55.61	gold quality
right atrium auricular region	UBERON:0006631	55.55	gold quality
cardiac atrium	UBERON:0002081	55.07	gold quality
esophagus	UBERON:0001043	54.73	gold quality
buccal mucosa cell	CL:0002336	53.24	gold quality
duodenum	UBERON:0002114	52.98	gold quality
decidua	UBERON:0002450	52.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	14.65
E-ANND-3	yes	6.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1B

miRNA regulators (miRDB)

8 targeting CDH16, 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-4283	100.00	66.42	2097
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-3620-3P	97.78	64.88	772
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-1287-5P	96.80	65.30	743

Literature-anchored findings (GeneRIF, showing 8)

• These results indicated that LIF induced multi-lineage differentiation of adult stem-like cells in kidney via cadherin 16. (PMID:15670782)
• Ksp-cadherin expression downregulated inrenal cell carcinoma; this cell adhesion molecule may have role in tumour suppression (PMID:15886705)
• Ksp-cad is a useful tumor type associated marker for distinguishing chromophobe renal cell carcinoma and renal oncocytoma from the wide range of nonintercalated cell-related adult renal epithelial neoplasms. (PMID:17895753)
• The interaction of Ksp-cadherin with alpha B-crystallin is important for the connection of Ksp-cadherin to the cytoskeleton and thus for maintaining tissue integrity in the kidney. (PMID:18343407)
• In thyroid carcinomas, as determined by quantitative RT-PCR, CDH16 expression decreases in papillary, follicular, and anaplastic thyroid carcinomas, and the decrease is more pronounced than that of CDH1. (PMID:22028439)
• Our study expands the clinical and allelic spectrum of known Retinal dystrophies genes, and reveals AGBL5, CDH16, and DNAJC17 as novel disease candidates. (PMID:26355662)
• Reduced CDH16 expression is linked to poor prognosis in clear cell renal cell carcinoma 16. (PMID:35606285)
• Loss of CDH16 expression is a strong independent predictor for lymph node metastasis in Middle Eastern papillary thyroid cancer. (PMID:37899424)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdh16	ENSMUSG00000031881
rattus_norvegicus	Cdh16	ENSRNOG00000012222

Paralogs (61): PCDHB4 (ENSG00000081818), PCDHA6 (ENSG00000081842), PCDHGA2 (ENSG00000081853), PCDHB2 (ENSG00000112852), PCDHB3 (ENSG00000113205), PCDHB5 (ENSG00000113209), PCDHB6 (ENSG00000113211), PCDHB7 (ENSG00000113212), PCDHB15 (ENSG00000113248), PCDH12 (ENSG00000113555), PCDH17 (ENSG00000118946), PCDHB8 (ENSG00000120322), PCDHB10 (ENSG00000120324), PCDHB14 (ENSG00000120327), PCDHB12 (ENSG00000120328), PCDH8 (ENSG00000136099), PCDH10 (ENSG00000138650), PCDH15 (ENSG00000150275), PCDH19 (ENSG00000165194), PCDHB1 (ENSG00000171815), PCDHB9 (ENSG00000177839), PCDHB13 (ENSG00000187372), CDHR4 (ENSG00000187492), PCDH18 (ENSG00000189184), PCDHB11 (ENSG00000197479), PCDHGA1 (ENSG00000204956), PCDHA9 (ENSG00000204961), PCDHA8 (ENSG00000204962), PCDHA7 (ENSG00000204963), PCDHA5 (ENSG00000204965), PCDHA4 (ENSG00000204967), PCDHA2 (ENSG00000204969), PCDHA1 (ENSG00000204970), PCDHA13 (ENSG00000239389), PCDHGC3 (ENSG00000240184), PCDHGC5 (ENSG00000240764), PCDHGC4 (ENSG00000242419), PCDHAC2 (ENSG00000243232), PCDHAC1 (ENSG00000248383), PCDHA11 (ENSG00000249158)

Protein

Protein identifiers

Cadherin-16 — O75309 (reviewed: O75309)

Alternative names: Kidney-specific cadherin

All UniProt accessions (6): A0A0B4J288, O75309, H3BSG2, H3BSV3, I3L418, J3QLA1

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. Kidney specific.

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?
O75309-1	1	yes
O75309-2	2
O75309-3	3
O75309-4	4

RefSeq proteins (4): NP_001191673, NP_001191674, NP_001191675, NP_004053* (*=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 (22 total): domain 6, glycosylation site 3, splice variant 3, sequence variant 3, topological domain 2, signal peptide 1, chain 1, region of interest 1, modified residue 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75309-F1	82.17	0.48

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): 822

Glycosylation sites (3): 517, 602, 722

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 121 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, chr16q22, PAX4_01, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, TGACCTY_ERR1_Q2, HNF1_Q6, GOBP_CALCIUM_DEPENDENT_CELL_CELL_ADHESION, PAX2_01, GOBP_CELL_CELL_ADHESION, BROWNE_HCMV_INFECTION_48HR_DN, RGTTAMWNATT_HNF1_01, DELYS_THYROID_CANCER_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP

GO Biological Process (4): cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), calcium-dependent cell-cell adhesion (GO:0016339), cell-cell adhesion (GO:0098609)

GO Molecular Function (4): calcium ion binding (GO:0005509), cell adhesion molecule binding (GO:0050839), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), synapse (GO:0045202), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	2
cellular process	1
cell adhesion	1
metal ion binding	1
protein binding	1
binding	1
cation binding	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
cell junction	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH16	PAX8	Q06710	507
CDH16	PAX2	Q02962	481
CDH16	KRT7	P08729	480
CDH16	AMACR	Q9UHK6	480
CDH16	AQP2	P41181	469
CDH16	TFE3	P19532	448
CDH16	PRCC	Q92733	428
CDH16	MIOX	Q9UGB7	424
CDH16	HNF1B	P35680	409
CDH16	FLCN	Q8NFG4	403
CDH16	MME	P08473	401
CDH16	AQP1	P29972	387
CDH16	CA9	Q16790	375
CDH16	CPO	Q8IVL8	361
CDH16	UMOD	P07911	360

IntAct

9 interactions, top by confidence:

A	B	Type	Score
KLK6	CDH16	psi-mi:“MI:0915”(physical association)	0.560
CDH16	RPL14	psi-mi:“MI:0915”(physical association)	0.400
CDH16	G6PC1	psi-mi:“MI:0915”(physical association)	0.370
	SHTN1	psi-mi:“MI:0914”(association)	0.350
CDH16	EGFR	psi-mi:“MI:0914”(association)	0.350
	CDH16	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): CDH16 (Affinity Capture-MS), RPL14 (Proximity Label-MS), CDH16 (Affinity Capture-MS), PTPRF (Affinity Capture-MS), SLC39A6 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), EFNB1 (Affinity Capture-MS), TFB2M (Affinity Capture-MS), CNTNAP3 (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), EGFR (Affinity Capture-MS), ICAM4 (Affinity Capture-MS), BLK (Affinity Capture-MS), DAG1 (Affinity Capture-MS), GAS6 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A6H8M9, D3YX43, O08644, O15197, O55134, O70394, O70540, O75309, O88338, P0C091, P0C0K6, P0C0K7, P0DP72, P21709, P40223, P59862, P70289, Q00657, Q04912, Q0V8J4, Q28634, Q501P1, Q53RD9, Q58Y75, Q5DRE2, Q5H8B9, Q5R6F5, Q5SZK8, Q60750, Q63315, Q64612, Q6MG64, Q6NVD0, Q6PFX6, Q6UVK1, Q76MJ5, Q7TN88, Q7Z442, Q86UP0

Diamond homologs: A0A8M2BIB6, E9PVD3, F1PAA9, F1QSQ0, H2EQR6, O18926, O35902, O55075, O55111, O75309, O95206, P08641, P12830, P24503, P30944, P32926, P33145, P33148, P33150, P33152, P33450, P55281, P55290, P55291, P55292, P55849, P55850, P79883, Q01107, Q03763, Q08554, Q12864, Q14126, Q28060, Q28634, Q3B7N0, Q3BDI7, Q5DRA9, Q5DRB0, Q5DRF2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
calcium(2+)	“up-regulates activity”	CDH16	“chemical activation”
CDH16	“up-regulates activity”	CTNNB1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	137
Likely benign	18
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3016 predictions. Top by Δscore:

Variant	Effect	Δscore
16:66909381:TCA:T	acceptor_gain	1.0000
16:66909382:CA:C	acceptor_gain	1.0000
16:66909382:CAC:C	acceptor_gain	1.0000
16:66909382:CACT:C	acceptor_loss	1.0000
16:66909383:AC:A	acceptor_loss	1.0000
16:66909384:C:CC	acceptor_gain	1.0000
16:66909384:CTG:C	acceptor_loss	1.0000
16:66909385:T:A	acceptor_loss	1.0000
16:66909980:TCTCA:T	donor_loss	1.0000
16:66909981:CTCAC:C	donor_loss	1.0000
16:66909982:TCACC:T	donor_loss	1.0000
16:66909983:CACC:C	donor_loss	1.0000
16:66909984:A:C	donor_loss	1.0000
16:66909985:C:CT	donor_loss	1.0000
16:66910090:GAACC:G	acceptor_loss	1.0000
16:66910091:AACCT:A	acceptor_loss	1.0000
16:66910093:CCT:C	acceptor_loss	1.0000
16:66910104:A:T	acceptor_gain	1.0000
16:66910397:G:GC	acceptor_gain	1.0000
16:66910405:G:C	acceptor_gain	1.0000
16:66910405:G:GC	acceptor_gain	1.0000
16:66910408:T:C	acceptor_gain	1.0000
16:66910408:T:TC	acceptor_gain	1.0000
16:66911894:CTCA:C	donor_loss	1.0000
16:66911895:TCAC:T	donor_loss	1.0000
16:66911896:CACCT:C	donor_loss	1.0000
16:66911897:A:C	donor_loss	1.0000
16:66911898:C:G	donor_loss	1.0000
16:66912313:C:A	donor_gain	1.0000
16:66912426:CCAAT:C	acceptor_gain	1.0000

AlphaMissense

5379 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:66915264:A:C	F180C	0.981
16:66915264:A:G	F180S	0.980
16:66915308:G:C	F165L	0.980
16:66915308:G:T	F165L	0.980
16:66915310:A:G	F165L	0.980
16:66912517:A:G	F449S	0.977
16:66909368:C:G	C764S	0.974
16:66909369:A:T	C764S	0.974
16:66910281:A:G	W716R	0.973
16:66910281:A:T	W716R	0.973
16:66914353:C:G	D215H	0.972
16:66909350:C:G	C770S	0.971
16:66909351:A:T	C770S	0.971
16:66910059:C:A	W734C	0.968
16:66910059:C:G	W734C	0.968
16:66910400:C:G	C676S	0.968
16:66910401:A:T	C676S	0.968
16:66912326:A:C	F488L	0.967
16:66912326:A:T	F488L	0.967
16:66912328:A:G	F488L	0.967
16:66915309:A:G	F165S	0.966
16:66916137:C:G	D118H	0.966
16:66916118:G:T	P124H	0.965
16:66912862:C:G	D362H	0.964
16:66912293:A:C	F499L	0.963
16:66912293:A:T	F499L	0.963
16:66912295:A:G	F499L	0.963
16:66915263:G:C	F180L	0.963
16:66915263:G:T	F180L	0.963
16:66915265:A:G	F180L	0.963

dbSNP variants (sampled 300 via entrez): RS1000184072 (16:66908667 C>T), RS1000890756 (16:66918991 G>A), RS1001151236 (16:66913918 G>A), RS1001164287 (16:66919164 C>T), RS1001479824 (16:66913836 A>G), RS1001500777 (16:66913667 G>A,T), RS1002219729 (16:66919799 G>A,T), RS1002223477 (16:66914006 G>A,T), RS1002274040 (16:66914198 T>C,G), RS1002292874 (16:66910672 C>G,T), RS1002478109 (16:66908908 C>A), RS1002558845 (16:66915153 G>A,T), RS1002572152 (16:66919614 C>T), RS1002611298 (16:66915470 C>T), RS1002781360 (16:66914454 G>A)

Disease associations

OMIM: gene MIM:603118 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST008075_198	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-07
GCST008075_97	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-08
GCST008084_177	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-07
GCST008084_62	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-09
GCST008085_72	HDL cholesterol levels in current drinkers	5.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Silicon Dioxide	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
2-tert-butylhydroquinone	decreases expression, increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
pentanal	decreases expression	1
ormosil	affects binding, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, increases methylation	1
Aldehydes	decreases expression	1
Arsenic	affects expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Plant Extracts	affects cotreatment, decreases expression	1
Polyethylene Glycols	affects binding, decreases expression	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1
Cadmium Chloride	increases expression	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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