CDH17

Summary

CDH17 (cadherin 17, HGNC:1756) is a protein-coding gene on chromosome 8q22.1, encoding Cadherin-17 (Q12864). Cadherins are calcium-dependent cell adhesion proteins.

This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. The encoded protein is cadherin-like, consisting of an extracellular region, containing 7 cadherin domains, and a transmembrane region but lacking the conserved cytoplasmic domain. The protein is a component of the gastrointestinal tract and pancreatic ducts, acting as an intestinal proton-dependent peptide transporter in the first step in oral absorption of many medically important peptide-based drugs. The protein may also play a role in the morphological organization of liver and intestine. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1015 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 160 total
• MANE Select transcript: NM_004063

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1756
Approved symbol	CDH17
Name	cadherin 17
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	HPT-1, cadherin
Ensembl gene	ENSG00000079112
Ensembl biotype	protein_coding
OMIM	603017
Entrez	1015

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 nonsense_mediated_decay

ENST00000027335, ENST00000441892, ENST00000450165, ENST00000520952, ENST00000521491, ENST00000877574, ENST00000877575, ENST00000877576, ENST00000877577, ENST00000877578, ENST00000877579, ENST00000877580, ENST00000877581, ENST00000877582, ENST00000951168, ENST00000951169, ENST00000951170, ENST00000951171

RefSeq mRNA: 13 — MANE Select: NM_004063 NM_001144663, NM_001413951, NM_001413952, NM_001413953, NM_001413954, NM_001413955, NM_001413956, NM_001413957, NM_001413958, NM_001413959, NM_001413960, NM_001413961, NM_004063

CCDS: CCDS6260

Canonical transcript exons

ENST00000027335 — 18 exons

Exon	Start	End
ENSE00000980940	94130876	94130992
ENSE00000980941	94130626	94130739
ENSE00000980942	94127162	94128340
ENSE00001024750	94145928	94146167
ENSE00001088917	94194635	94194705
ENSE00001088921	94173797	94173996
ENSE00001088926	94170397	94170547
ENSE00001088927	94170854	94170985
ENSE00001227798	94151868	94152112
ENSE00001227809	94159971	94160162
ENSE00001227819	94162086	94162162
ENSE00001227827	94165761	94165976
ENSE00001227862	94174102	94174260
ENSE00001227870	94176541	94176679
ENSE00001227879	94177587	94177721
ENSE00001227889	94189187	94189285
ENSE00002106993	94208483	94208555
ENSE00003573922	94148744	94148874

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 99.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.0965 / max 984.4487, expressed in 98 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93976	3.0232	90
93978	0.0284	5
93977	0.0207	7
93979	0.0160	4
93980	0.0083	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic mucosa	UBERON:0000317	99.49	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.45	gold quality
ileal mucosa	UBERON:0000331	99.22	gold quality
jejunal mucosa	UBERON:0000399	99.18	gold quality
ileum	UBERON:0002116	99.18	gold quality
rectum	UBERON:0001052	99.05	gold quality
mucosa of transverse colon	UBERON:0004991	98.74	gold quality
duodenum	UBERON:0002114	95.57	gold quality
pancreatic ductal cell	CL:0002079	91.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.50	gold quality
secondary oocyte	CL:0000655	91.12	gold quality
small intestine	UBERON:0002108	90.69	gold quality
transverse colon	UBERON:0001157	90.68	gold quality
vermiform appendix	UBERON:0001154	89.06	gold quality
caecum	UBERON:0001153	88.37	gold quality
oocyte	CL:0000023	87.74	gold quality
colonic epithelium	UBERON:0000397	85.11	gold quality
intestine	UBERON:0000160	84.93	gold quality
epithelial cell of pancreas	CL:0000083	83.04	silver quality
large intestine	UBERON:0000059	82.83	gold quality
colon	UBERON:0001155	82.09	gold quality
jejunum	UBERON:0002115	80.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.28	gold quality
islet of Langerhans	UBERON:0000006	76.30	gold quality
buccal mucosa cell	CL:0002336	71.58	silver quality
smooth muscle tissue	UBERON:0001135	70.93	gold quality
sigmoid colon	UBERON:0001159	68.74	gold quality
gall bladder	UBERON:0002110	68.52	gold quality
palpebral conjunctiva	UBERON:0001812	65.38	gold quality
muscle layer of sigmoid colon	UBERON:0035805	61.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	48.95
E-ANND-3	yes	18.19
E-GEOD-125970	yes	15.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ARID1A, CDX2, CTBP2, DNMT1, DNMT3B, EGR1, ESR1, ESR2, EZH2, FOXA1, FOXA2, FOXC1, FOXM1, FOXO3, FOXQ1, GATA3, GCM1, GLI1, HMGA2, HNF1A, ID1, JUN, KDM5A, KLF2, KLF4, KLF8, LMO2, MTA1, MXD1, MYC, NCOA3, NEUROD1, PARP1, PAX8, PPARG, PROX1, RARB, REST, SNAI1

miRNA regulators (miRDB)

70 targeting CDH17, 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-6873-3P	100.00	71.42	2626
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 40)

• High xpression of liver-intestine cadherin and its possible interaction with galectin-3 is associated with ductal adenocarcinoma of the pancreas (PMID:12824888)
• tumor staging and LI-cadherin expression were found to be independent factors associated with lymph node metastasis. (PMID:15178443)
• LI-cadherin may have a role in lymph node metastasis and progression of human colorectal carcinoma (PMID:15279905)
• Aberrant alternative splicing of LI-cadherin is associated with hepatocellular carcinoma (PMID:15701831)
• The functional T-G haplotype of CDH17 (651 C>T and IVS6+35A>G) is a genetic susceptibility factor for the development of Hepatocellular carcinoma (HCC) in a Chinese population. (PMID:16951245)
• Reduced expression of liver intestine-cadherin had a significant correlation with tumoral dedifferentiation and short overall survival in colorectal cancer. (PMID:17828401)
• The heterotypic trans-interaction of LI- and E-cadherin might play a role during development of the intestinal epithelium when the cells do not yet have elaborate membrane specializations. (PMID:18342884)
• combined detection of CDH17/CDX2 co-expression may benefit us in predicting the prognosis of gastric carcinoma. (PMID:18353622)
• Cadherin-17 is a useful immunohistochemical marker for diagnosis of adenocarcinomas of the digestive system. (PMID:18552820)
• CDH17 is a novel oncogene in hepatocellular carcinoma. CDH17 is a biomarker and attractive therapeutic target for this aggressive malignancy. (PMID:19676131)
• Loss of LI-cadherin results in up-regulation of MTF-1 and PlGF, thereby regulating angiogenesis in intrahepatic cholangiocarcinoma (PMID:19956853)
• Li-cadherin participates in the multiple steps of invasion and metastasis in a colorectal cancer cell line. (PMID:20204409)
• we proposed that CDH17 may be an oncogene up-regulating invasive features of gastric cancer cells (PMID:20393816)
• Expression of CDH17 and MUC13 was up-regulated in gastric cancer tissues. CDH17 is a promising prognostic marker for early stage gastric cancer. (PMID:20398667)
• CDX2 and LI-cadherin are sensitive markers of intestinal metaplasia with or without dysplasia in the upper gastrointestinal tract. (PMID:20444732)
• CDH17 maybe a positive regulator for proliferative, adhesive, and invasive behaviors of gastric cancer. (PMID:20500517)
• identified the minimal promoter region of CDH17 that is regulated by HNF1alpha and CDX2 transcriptional factors; Suppression of HNF1alpha and CDX2 expression by siRNA down-regulated expressions of CDH17 and cyclin D1 and the viability of HCC cells (PMID:20568120)
• Targeting CDH17 in HCC can inhibit tumor growth and inactivate Wnt signaling pathway in concomitance with activation of tumor suppressor genes.[review] (PMID:20580775)
• CDH17 expression may be well preserved during the metastatic process and therefore be a useful marker for identifying colorectal adenocarcinomas in a metastatic setting with an unknown primary site (PMID:21323956)
• CDH17 was positively associated with larger tumor size, deeper invasion, diffuse/mixed histotype, LVI, and LNMM, predicting a poor prognosis in pN0 gastric cancer. (PMID:22009269)
• LI cadherin is associated with an intestinal phenotype and an ‘intestinal pathway’ of carcinogenesis in intraductal papillary mucinous neoplasm. (PMID:22286087)
• Report less aggressive behavior of gastric tumors after CDH17 gene knockdown. (PMID:22791949)
• Up-regulation of cadherin 17 is associated with epithelial ovarian cancer progression. (PMID:22810971)
• LI-cadherin is a sensitive marker of intestinal metaplasia and can be helpful for early histologic diagnosis of Barrett’s esophagus (BE); it is not, however, significantly different between BE with and without intestinal epithelial neoplasia. (PMID:23053896)
• Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFkappaB signaling pathway. (PMID:23298905)
• The SNPs of the CDH17 gene c.2216 A>C might be clinically important in the prognosis of colorectal carcinoma. (PMID:23326130)
• results identify CDH17 as a biomarker of gastric carcinoma and attractive therapeutic target for this aggressive malignancy. (PMID:23554857)
• This study demonstrates that the secreted form of cadherin-17 (ectodomain) is truncated at the C-terminus. (PMID:23557862)
• Data reveal a new function for CDH17, which is to regulate alpha2beta1 integrin signaling in cell adhesion and proliferation in colon cancer cells for liver metastasis. (PMID:23604127)
• Data suggest that combined tumor expression of CDH17 (cadherin-17) and SATB2 (special AT-rich sequence binding protein 2) may be used as diagnostic biomarkers in subjects with medullary carcinoma of the large intestine (colon; cecum). (PMID:24437456)
• RGD motif present in cadherin 17 induces integrin activation and tumor growth (PMID:25336636)
• CDH17 is a sensitive marker for midgut WDNETs, and the CDH17+/CDX2-/TTF1- phenotype was found to be sensitive (92%) and specific (91%) for hindgut well-differentiated neuroendocrine tumours (WDNETs). (PMID:25388236)
• CDH17 is a sensitive (81%) and highly specific (100%) marker for metanephric adenoma. (PMID:25768256)
• Review/Meta-analysis: data reflect the role of CDH17 in tumor proliferation and metastasis among gastric cancer patients. (PMID:25834338)
• Mutations in CDH17 gene is associated with idiopathic hypereosinophilic syndrome. (PMID:26497854)
• Fascin-1 expression, cadherin-17 expression, tumor size, and differentiation were independent risk factors for GC. (PMID:26743780)
• These data indicate that knockdown of LIcadherin facilitates the invasion of cancer cells by degrading extracellular matrix components via activation of MMP2 and 9, and increases cancer cell adhesion and migration via altered expression of galectin3. (PMID:27035870)
• CDH17 and CLDN18 are useful target molecules. Their coupling can aid in the comprehensive detection and localization of gastric cancer metastases in vivo to overcome challenges associated with intratumoral heterogeneity. (PMID:27580354)
• Using a lentiviral system as a delivery mediator of RNA interference, we found that inhibition of CDH17 can lead to reduce proliferation and increase apoptosis of gastric cancer cell line MKN28 in vitro and significantly diminish their tumorigenicity in vivo. Our results of the present study suggest that CDH17 may be a promising candidate for the therapeutic targeting of gastric cancer. (PMID:27909714)
• In stomach adenocarcinomas, CDH17 positively stained 64.0% (112 of 175) of tissues, compared to CK20 and CDX2, where staining was observed in only 24.6% (43 of 175) and 46.9% (82 of 175), respectively. (PMID:28029907)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdh17	ENSDARG00000005112
mus_musculus	Cdh17	ENSMUSG00000028217
rattus_norvegicus	Cdh17	ENSRNOG00000015562

Paralogs (33): CDH1 (ENSG00000039068), CDH10 (ENSG00000040731), CDH3 (ENSG00000062038), CDH19 (ENSG00000071991), CDHR2 (ENSG00000074276), 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), CDH12 (ENSG00000154162), PCDH1 (ENSG00000156453), DCHS1 (ENSG00000166341), PCDH7 (ENSG00000169851), CDH2 (ENSG00000170558), CDH4 (ENSG00000179242), CDH5 (ENSG00000179776), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410), PCDH20 (ENSG00000280165)

Protein

Protein identifiers

Cadherin-17 — Q12864 (reviewed: Q12864)

Alternative names: Intestinal peptide-associated transporter HPT-1, Liver-intestine cadherin

All UniProt accessions (4): Q12864, E5RJT3, E7EN24, H0YBL0

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. LI-cadherin may have a role in the morphological organization of liver and intestine. Involved in intestinal peptide transport.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the gastrointestinal tract and pancreatic duct. Not detected in kidney, lung, liver, brain, adrenal gland and skin.

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 (13): NP_001138135, NP_001400880, NP_001400881, NP_001400882, NP_001400883, NP_001400884, NP_001400885, NP_001400886, NP_001400887, NP_001400888, NP_001400889, NP_001400890, NP_004054* (*=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 (66 total): strand 31, glycosylation site 8, turn 8, domain 7, sequence variant 4, helix 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7EV1	X-RAY DIFFRACTION	1.38
6ULM	X-RAY DIFFRACTION	2.15
7CYM	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12864-F1	86.98	0.61

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 (8): 149, 184, 250, 419, 456, 546, 587, 722

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: 196 (showing top): GOBP_B_CELL_ACTIVATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOCC_CELL_SURFACE, HNF1_Q6, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CALCIUM_DEPENDENT_CELL_CELL_ADHESION, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_CELL_CELL_ADHESION, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_HEMATOPOIETIC_OR_LYMPHOID_ORGAN_DEVELOPMENT, RYTAAWNNNTGAY_UNKNOWN, HOSHIDA_LIVER_CANCER_LATE_RECURRENCE_DN, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY

GO Biological Process (17): cell morphogenesis (GO:0000902), germinal center B cell differentiation (GO:0002314), marginal zone B cell differentiation (GO:0002315), oligopeptide transport (GO:0006857), cell-cell junction assembly (GO:0007043), cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), integrin-mediated signaling pathway (GO:0007229), calcium-dependent cell-cell adhesion (GO:0016339), cell migration (GO:0016477), positive regulation of integrin activation by cell surface receptor linked signal transduction (GO:0033626), adherens junction organization (GO:0034332), cell-cell adhesion mediated by cadherin (GO:0044331), spleen development (GO:0048536), B cell differentiation (GO:0030183), oligopeptide transmembrane transport (GO:0035672), cell-cell adhesion (GO:0098609)

GO Molecular Function (7): integrin binding (GO:0005178), proton-dependent oligopeptide secondary active transmembrane transporter activity (GO:0005427), calcium ion binding (GO:0005509), beta-catenin binding (GO:0008013), cadherin binding (GO:0045296), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), adherens junction (GO:0005912), cell surface (GO:0009986), basolateral plasma membrane (GO:0016323), catenin complex (GO:0016342), cell junction (GO:0030054), 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
cellular anatomical structure	4
cell-cell adhesion	3
mature B cell differentiation involved in immune response	2
cell-cell junction organization	2
cell surface receptor signaling pathway	2
cell adhesion molecule binding	2
anatomical structure morphogenesis	1
peptide transport	1
nitrogen compound transport	1
cell junction assembly	1
cellular process	1
cell motility	1
integrin activation	1
positive regulation of integrin activation	1
hematopoietic or lymphoid organ development	1
lymphocyte differentiation	1
B cell activation	1
oligopeptide transport	1
transmembrane transport	1
cell adhesion	1
signaling receptor binding	1
protein-containing complex binding	1
secondary active transmembrane transporter activity	1
metal ion binding	1
protein binding	1
binding	1
cation binding	1
nuclear lumen	1
membrane	1
cell periphery	1
cell-cell junction	1
basal plasma membrane	1
plasma membrane region	1
extrinsic component of plasma membrane	1
plasma membrane protein complex	1

Protein interactions and networks

STRING

4496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH17	CTNNB1	P35222	999
CDH17	CTNND1	O60716	998
CDH17	PECAM1	P16284	995
CDH17	NECTIN1	Q15223	992
CDH17	KDR	P35968	991
CDH17	CTNND2	Q9UQB3	991
CDH17	VCL	P18206	990
CDH17	CTNNA1	P35221	964
CDH17	TJP1	Q07157	950
CDH17	OCLN	Q16625	949
CDH17	KLRG1	Q96E93	929
CDH17	DSP	P15924	925
CDH17	PSEN1	P49768	925
CDH17	CLDN5	O00501	885
CDH17	AFDN	P55196	871

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CDH17	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
CDH17	TNFSF9	psi-mi:“MI:0914”(association)	0.350
CDH17	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): UBQLN2 (Two-hybrid), CDH17 (Affinity Capture-MS), CDH17 (Proximity Label-MS), CDH17 (Proximity Label-MS), PCDH18 (Affinity Capture-MS), PCDHGC3 (Affinity Capture-MS), TMTC4 (Affinity Capture-MS), TNFSF9 (Affinity Capture-MS)

ESM2 similar proteins: E9Q7P9, O88277, O93319, P55280, P55281, P55285, P55289, P70408, P79995, P97326, Q08DJ5, Q12864, Q13634, Q14517, Q24298, Q2PZL6, Q3SWX5, Q5DWV1, Q5DWV2, Q5F226, Q63315, Q6B3P0, Q6KEQ9, Q6V0I7, Q6WXV7, Q6WYY1, Q6X862, Q6ZTQ4, Q71M42, Q8BIZ0, Q8BL00, Q8BM92, Q8BNA6, Q8N6Y1, Q8QGH3, Q8R508, Q8TDW7, Q90762, Q90763, Q91838

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

4 interactions.

A	Effect	B	Mechanism
CDX2	“up-regulates quantity by expression”	CDH17	“transcriptional regulation”
HNF1A	“up-regulates quantity by expression”	CDH17	“transcriptional regulation”
calcium(2+)	“up-regulates activity”	CDH17	“chemical activation”
CDH17	“up-regulates activity”	CTNNB1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	127
Likely benign	8
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2581 predictions. Top by Δscore:

Variant	Effect	Δscore
8:94130871:TCTAC:T	donor_loss	1.0000
8:94130872:CTAC:C	donor_loss	1.0000
8:94130873:TACC:T	donor_loss	1.0000
8:94130875:CC:C	donor_loss	1.0000
8:94130896:T:TA	donor_gain	1.0000
8:94146163:CCCCC:C	acceptor_gain	1.0000
8:94146164:CCCCC:C	acceptor_gain	1.0000
8:94148881:CAAA:C	acceptor_gain	1.0000
8:94159966:TTTA:T	donor_loss	1.0000
8:94159967:TTA:T	donor_loss	1.0000
8:94159968:TACC:T	donor_loss	1.0000
8:94159969:A:AT	donor_loss	1.0000
8:94159970:C:CG	donor_loss	1.0000
8:94160073:C:CA	donor_gain	1.0000
8:94160158:CCATA:C	acceptor_gain	1.0000
8:94160159:CATA:C	acceptor_gain	1.0000
8:94160159:CATAC:C	acceptor_gain	1.0000
8:94160160:ATAC:A	acceptor_loss	1.0000
8:94160161:TA:T	acceptor_gain	1.0000
8:94160161:TAC:T	acceptor_loss	1.0000
8:94160162:ACTAA:A	acceptor_loss	1.0000
8:94160163:C:CA	acceptor_loss	1.0000
8:94160163:C:CC	acceptor_gain	1.0000
8:94160164:T:C	acceptor_loss	1.0000
8:94162084:A:AC	donor_gain	1.0000
8:94162085:C:CC	donor_gain	1.0000
8:94162085:CAT:C	donor_gain	1.0000
8:94165757:TAA:T	donor_loss	1.0000
8:94165758:AACC:A	donor_loss	1.0000
8:94165759:A:AC	donor_gain	1.0000

AlphaMissense

5494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:94162105:G:T	P447H	0.992
8:94173954:A:G	L209P	0.991
8:94176613:C:G	D118H	0.990
8:94170870:C:G	R300P	0.989
8:94173863:C:A	W239C	0.989
8:94173863:C:G	W239C	0.989
8:94174117:A:G	S190P	0.989
8:94173865:A:G	W239R	0.988
8:94173865:A:T	W239R	0.988
8:94159984:A:T	V513D	0.987
8:94174225:C:G	D154H	0.987
8:94162105:G:C	P447R	0.986
8:94162116:A:C	N443K	0.985
8:94162116:A:T	N443K	0.985
8:94174119:A:T	I189N	0.985
8:94174242:A:T	V148D	0.985
8:94174146:A:G	F180S	0.984
8:94174236:G:T	A150D	0.984
8:94176594:G:T	P124H	0.984
8:94160057:A:C	Y489D	0.983
8:94160101:G:T	A474D	0.983
8:94177591:A:G	L94P	0.983
8:94152067:C:G	A533P	0.982
8:94162099:A:C	F449C	0.981
8:94165940:T:G	D368A	0.981
8:94165941:C:G	D368H	0.981
8:94173937:C:G	D215H	0.981
8:94176612:T:G	D118A	0.981
8:94162099:A:G	F449S	0.980
8:94174224:T:G	D154A	0.980

dbSNP variants (sampled 300 via entrez): RS1000034615 (8:94217325 C>G), RS1000067947 (8:94175659 G>A), RS1000076083 (8:94128631 A>G), RS1000128211 (8:94128300 A>G), RS1000150846 (8:94211514 T>C,G), RS1000190711 (8:94159572 C>T), RS1000197228 (8:94169647 C>A,T), RS1000200178 (8:94163000 C>A), RS1000207685 (8:94154264 C>T), RS1000248386 (8:94182417 T>C), RS1000281167 (8:94136400 C>A,T), RS1000355281 (8:94215960 T>C), RS1000360934 (8:94205176 T>G), RS1000414727 (8:94172753 G>C), RS1000422543 (8:94199615 A>G)

Disease associations

OMIM: gene MIM:603017 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): megacolon (MONDO:0001273)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002875_129	Diisocyanate-induced asthma	1.000000e-08
GCST004387_1	Pulse pressure	6.000000e-12
GCST004388_8	Blood pressure traits (multi-trait analysis)	2.000000e-13
GCST006168_6	Pulse pressure x alcohol consumption interaction (2df test)	1.000000e-08
GCST010796_2197	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_2198	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09
GCST010866_131	Coronary artery disease	1.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004329	alcohol drinking
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008531	Megacolon	C06.405.469.158.701

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression	2
ethyl-p-hydroxybenzoate	decreases expression	1
zinc chloride	decreases expression	1
butyraldehyde	decreases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases expression, decreases reaction, increases expression	1
sulindac sulfide	decreases expression	1
bathocuproine sulfonate	affects cotreatment, decreases expression, decreases reaction, increases expression	1
casticin	increases expression	1
CGP 52608	increases reaction, affects binding	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Cocaine	decreases expression	1
Curcumin	decreases expression	1
Silicon Dioxide	decreases expression	1
Tetradecanoylphorbol Acetate	affects cotreatment, decreases expression, decreases reaction	1
Ionomycin	decreases expression, decreases reaction, affects cotreatment	1
Crack Cocaine	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	affects expression	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E4IN	Genomeditech HCT116 H_CDH17	Cancer cell line	Male
CVCL_E6TH	Genomeditech HEK-293 H_CDH17	Transformed cell line	Female
CVCL_E8SI	SNU-16 CDH17 KO clone 1C1	Cancer cell line	Female
CVCL_E8SJ	SNU-16 CDH17 KO clone 2A1	Cancer cell line	Female
CVCL_F1MR	HyCyte AsPC-1 KO-hCDH17	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04340856	Not specified	COMPLETED	Retrospective, Uncontrolled Cohort Study on the Therapy of Chronic Megalon
NCT07470892	Not specified	NOT_YET_RECRUITING	Preoperative Fish Oil PN and Prognosis After Constipation Surgery