CLDN17

Summary

CLDN17 (claudin 17, HGNC:2038) is a protein-coding gene on chromosome 21q21.3, encoding Claudin-17 (P56750). Channel-forming tight junction protein with selectivity for anions, including chloride and hydrogencarbonate, and for solutes smaller than 9 Angstrom in diameter.

This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. This gene is intronless and is clustered with CLDN8 on chromosome 21q22.11.

Source: NCBI Gene 26285 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_012131

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2038
Approved symbol	CLDN17
Name	claudin 17
Location	21q21.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC126552, MGC126554
Ensembl gene	ENSG00000156282
Ensembl biotype	protein_coding
OMIM	617005
Entrez	26285

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000286808

RefSeq mRNA: 1 — MANE Select: NM_012131 NM_012131

CCDS: CCDS13586

Canonical transcript exons

ENST00000286808 — 1 exons

Exon	Start	End
ENSE00001025582	30165565	30166805

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 85.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1750 / max 268.6853, expressed in 10 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190106	0.1235	6
190105	0.0153	3
190108	0.0113	2
190103	0.0107	3
190107	0.0089	2
190104	0.0054	1

Top tissues by expression

258 total, 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	85.94	gold quality
lower esophagus mucosa	UBERON:0035834	75.93	gold quality
cervix epithelium	UBERON:0004801	74.57	silver quality
oral cavity	UBERON:0000167	71.72	gold quality
ileal mucosa	UBERON:0000331	71.55	silver quality
cervix squamous epithelium	UBERON:0006922	69.39	gold quality
buccal mucosa cell	CL:0002336	68.43	silver quality
esophagus mucosa	UBERON:0002469	66.77	gold quality
penis	UBERON:0000989	65.79	gold quality
tongue squamous epithelium	UBERON:0006919	64.81	silver quality
tibialis anterior	UBERON:0001385	64.54	silver quality
oviduct epithelium	UBERON:0004804	62.26	silver quality
amniotic fluid	UBERON:0000173	58.28	gold quality
tendon of biceps brachii	UBERON:0008188	57.15	gold quality
deltoid	UBERON:0001476	57.05	gold quality
diaphragm	UBERON:0001103	56.99	gold quality
vastus lateralis	UBERON:0001379	56.54	gold quality
quadriceps femoris	UBERON:0001377	56.53	gold quality
pancreatic ductal cell	CL:0002079	56.19	silver quality
epithelium of esophagus	UBERON:0001976	56.09	silver quality
sperm	CL:0000019	55.76	gold quality
male germ cell	CL:0000015	55.55	gold quality
gingiva	UBERON:0001828	54.40	gold quality
esophagus squamous epithelium	UBERON:0006920	53.40	silver quality
vagina	UBERON:0000996	52.82	gold quality
body of tongue	UBERON:0011876	52.47	silver quality
triceps brachii	UBERON:0001509	52.43	gold quality
uterine cervix	UBERON:0000002	51.45	gold quality
epithelial cell of pancreas	CL:0000083	50.54	gold quality
tongue	UBERON:0001723	50.47	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.64

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• CLDN17, clustered with CLDN8 at human chromosome 21q22.11, is a four-transmembrane protein with WWCC motif, defined by W-X(17-22)-W-X(2)-C-X(8-10)-C. (PMID:12736707)
• Claudin 17 expression was down-regulated in gastric cancer. (PMID:24325792)
• The structural features of Cldn17 contributing to anion channel formation are presented in this work. (PMID:26194246)
• that the upregulated expression of CLDN17 significantly enhances the migration ability of hepatocytes in vitro and we found that the activation of the Stat3 pathway by Tyk2 may an important mechanism by which CLDN17 promotes aggressiveness in hepatocytes (PMID:30219077)
• Tight junction protein CLDN17 serves as a tumor suppressor to reduce the invasion and migration of oral cancer cells by inhibiting epithelial-mesenchymal transition. (PMID:34781072)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cldn17	ENSMUSG00000055811

Paralogs (22): CLDN11 (ENSG00000013297), CLDN18 (ENSG00000066405), CLDN15 (ENSG00000106404), CLDN16 (ENSG00000113946), CLDN10 (ENSG00000134873), CLDN8 (ENSG00000156284), CLDN14 (ENSG00000159261), CLDN1 (ENSG00000163347), CLDN19 (ENSG00000164007), CLDN3 (ENSG00000165215), CLDN2 (ENSG00000165376), CLDN20 (ENSG00000171217), CLDN22 (ENSG00000177300), CLDN7 (ENSG00000181885), CLDN5 (ENSG00000184113), CLDN6 (ENSG00000184697), CLDN24 (ENSG00000185758), CLDN4 (ENSG00000189143), CLDN9 (ENSG00000213937), CLDN25 (ENSG00000228607), CLDN34 (ENSG00000234469), CLDN23 (ENSG00000253958)

Protein

Protein identifiers

Claudin-17 — P56750 (reviewed: P56750)

All UniProt accessions (1): P56750

UniProt curated annotations — full annotation on UniProt →

Function. Channel-forming tight junction protein with selectivity for anions, including chloride and hydrogencarbonate, and for solutes smaller than 9 Angstrom in diameter. In the kidney proximal tubule, may be involved in paracellular reabsorption of filtered anions. Does not affect water permeability.

Subunit / interactions. Cannot form tight junction strands on its own. Interacts with OCLN.

Subcellular location. Cell junction. Tight junction. Basolateral cell membrane.

Tissue specificity. In the kidney, expressed in the proximal tubule and in the Henle’s loop. In the distal convoluted tubule, not expressed in all tubules. Not detected in the collecting duct (at protein level).

Similarity. Belongs to the claudin family.

RefSeq proteins (1): NP_036263* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR006187	Claudin	Family
IPR017974	Claudin_CS	Conserved_site

Pfam: PF00822

Catalyzed reactions (Rhea), 7 shown:

• hydrogencarbonate(in) = hydrogencarbonate(out) (RHEA:28695)
• chloride(in) = chloride(out) (RHEA:29823)
• nitrate(in) = nitrate(out) (RHEA:34923)
• iodide(out) = iodide(in) (RHEA:66324)
• thiocyanate(in) = thiocyanate(out) (RHEA:75347)
• bromide(in) = bromide(out) (RHEA:75383)
• fluoride(in) = fluoride(out) (RHEA:76159)

UniProt features (25 total): mutagenesis site 14, topological domain 5, transmembrane region 4, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56750-F1	77.86	0.31

Functional residue map

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

Mutagenesis-validated functional residues (14):

Position	Phenotype
31	decreased transepithelial resistance and anion selectivity. higher permeability to chloride, sodium and also to larger a
44	decreased transepithelial resistance and anion selectivity.
45	decreased transepithelial resistance, no effect on anion selectivity.
48	decreased transepithelial resistance and anion selectivity. higher permeability to chloride, sodium and also to larger a
56	no effect on transepithelial resistance, nor on anion selectivity. elevated permeabilities not only for chloride, but al
56	decreased anion selectivity. increased permeabilities not only for chloride, but also for sodium and thiocyanate. no eff
59	no effect on transepithelial resistance, nor on anion selectivity. increased permeability for thiocyanate.
61	decreased anion selectivity. no effect on transepithelial resistance.
65	reduced channel formation ability. increased transepithelial resistance. loss of anion selectivity in favor of cation se
65	no effect on channel formation ability. loss of anion selectivity in favor of cation selectivity. no effect on transepit
65	strongly reduced channel formation ability. increased transepithelial resistance. loss of anion selectivity in favor of
68	increased transepithelial resistance. loss of anion selectivity in favor of cation (sodium) selectivity.
149	increased transepithelial resistance. no effect on localization to cell-cell junctions.
154	loss of anion selectivity. strongly increased permeabilities not only for chloride, but also for sodium and the larger a

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions

MSigDB gene sets: 69 (showing top): GOBP_INORGANIC_ANION_TRANSPORT, KEGG_TIGHT_JUNCTION, GOBP_CELL_CELL_ADHESION, GOBP_CHLORIDE_TRANSPORT, GGARNTKYCCA_UNKNOWN, TGANTCA_AP1_C, GOCC_CELL_CELL_JUNCTION, GOBP_TRANSMEMBRANE_TRANSPORT, KEGG_CELL_ADHESION_MOLECULES_CAMS, AR_Q2, TGGAAA_NFAT_Q4_01, TAATTA_CHX10_01, GOCC_CHLORIDE_CHANNEL_COMPLEX, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX

GO Biological Process (8): cell adhesion (GO:0007155), calcium-independent cell-cell adhesion (GO:0016338), bicellular tight junction assembly (GO:0070830), paracellular transport (GO:0160184), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), chloride transmembrane transport (GO:1902476)

GO Molecular Function (6): structural molecule activity (GO:0005198), chloride channel activity (GO:0005254), channel activity (GO:0015267), identical protein binding (GO:0042802), paracellular tight junction channel activity (GO:0160187), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), basolateral plasma membrane (GO:0016323), chloride channel complex (GO:0034707), tight junction (GO:0070160), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cell-cell junction organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
cellular process	1
cell-cell adhesion	1
apical junction assembly	1
tight junction assembly	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
molecular_function	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
passive transmembrane transporter activity	1
protein binding	1
transporter activity	1
binding	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
basal plasma membrane	1
plasma membrane region	1
monoatomic ion channel complex	1
cell-cell junction	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN17	CLDN12	P56749	823
CLDN17	CLDN16	Q9Y5I7	604
CLDN17	CLDN25	C9JDP6	500
CLDN17	GRIK1	P39086	474
CLDN17	FREM3	P0C091	458
CLDN17	CLDN34	H7C241	453
CLDN17	SLC35F1	Q5T1Q4	447
CLDN17	OTOR	Q9NRC9	418
CLDN17	PATJ	Q8NI35	415
CLDN17	ABCA13	Q86UQ4	412
CLDN17	SCAF4	O95104	390
CLDN17	MARVELD2	Q8N4S9	374
CLDN17	PGLYRP4	Q96LB8	374
CLDN17	PGLYRP3	Q96LB9	374
CLDN17	THSD7B	Q9C0I4	374

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CLDN17	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.400
CLDN17	ZDHHC6	psi-mi:“MI:0915”(physical association)	0.400
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): CLDN17 (Affinity Capture-MS), CLDN17 (Proximity Label-MS), ZDHHC6 (Affinity Capture-MS), CLDN17 (Two-hybrid), CLDN17 (Biochemical Activity)

ESM2 similar proteins: A0A8C0N7E5, C3VMW3, D3ZQJ0, O00501, O14493, O15551, O19005, O35054, O35912, O54942, O88551, O95471, O95484, O95832, P56745, P56746, P56747, P56748, P56750, P78369, Q2HJ22, Q2KIY2, Q3B7N4, Q5E9L0, Q5QT56, Q5R8E5, Q63400, Q6BBL6, Q6DHB5, Q6DHP1, Q6L708, Q765N9, Q8BXA6, Q8N6F1, Q95KM5, Q9D1D1, Q9ET38, Q9JKD6, Q9QYW5, Q9YH90

Diamond homologs: A0A8C0N7E5, A6NM45, C3VMW3, C9JDP6, D3ZQJ0, O00501, O14493, O15551, O19005, O35054, O54942, O75508, O88551, O88552, O95471, O95484, O95500, O95832, P56745, P56746, P56747, P56748, P56750, P56856, P56857, P56880, P57739, P78369, Q0VCN0, Q2HJ22, Q2KIY2, Q3B7N4, Q3MHK4, Q4R3L1, Q5E9L0, Q5I0E5, Q5QT56, Q5R8E5, Q60771, Q63400

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LNX1	“down-regulates quantity by destabilization”	CLDN17	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

278 predictions. Top by Δscore:

Variant	Effect	Δscore
21:30166342:C:CT	acceptor_gain	0.7900
21:30166343:A:T	acceptor_gain	0.7800
21:30166625:A:AC	donor_gain	0.7700
21:30166626:C:CC	donor_gain	0.7700
21:30166216:C:CT	acceptor_gain	0.7600
21:30165878:CAG:C	donor_gain	0.6300
21:30165878:C:CG	donor_gain	0.6200
21:30166210:C:CT	acceptor_gain	0.6100
21:30165878:CAGT:C	donor_gain	0.5900
21:30166619:G:A	donor_gain	0.5900
21:30165877:A:AC	donor_gain	0.5800
21:30166085:C:G	acceptor_gain	0.5700
21:30165907:TTG:T	donor_gain	0.5600
21:30166164:C:A	acceptor_gain	0.5600
21:30166487:T:TG	acceptor_gain	0.5500
21:30165878:CA:C	donor_gain	0.5400
21:30166113:A:T	acceptor_gain	0.5400
21:30165908:TG:T	donor_gain	0.5300
21:30166068:C:CT	acceptor_gain	0.5300
21:30166627:T:C	donor_gain	0.5300
21:30165878:CAGTT:C	donor_gain	0.5200
21:30166488:C:G	acceptor_gain	0.5200
21:30166061:C:CT	acceptor_gain	0.5100
21:30166620:CCT:C	donor_gain	0.5100
21:30165995:T:C	donor_gain	0.5000
21:30166211:G:T	acceptor_gain	0.5000
21:30166317:C:CT	acceptor_gain	0.5000
21:30165874:CTTA:C	donor_gain	0.4900
21:30166059:A:T	acceptor_gain	0.4900
21:30166087:A:T	acceptor_gain	0.4900

AlphaMissense

1437 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:30166528:C:A	W30C	0.984
21:30166528:C:G	W30C	0.984
21:30166174:G:C	F148L	0.983
21:30166174:G:T	F148L	0.983
21:30166176:A:G	F148L	0.983
21:30166530:A:G	W30R	0.973
21:30166530:A:T	W30R	0.973
21:30166473:C:G	G49R	0.971
21:30166473:C:T	G49R	0.971
21:30166105:G:C	S171R	0.969
21:30166105:G:T	S171R	0.969
21:30166107:T:G	S171R	0.969
21:30166204:G:C	S138R	0.964
21:30166204:G:T	S138R	0.964
21:30166206:T:G	S138R	0.964
21:30166473:C:A	G49W	0.963
21:30166513:A:C	F35L	0.961
21:30166513:A:T	F35L	0.961
21:30166515:A:G	F35L	0.961
21:30166113:A:G	W169R	0.960
21:30166113:A:T	W169R	0.960
21:30166427:C:G	C64S	0.959
21:30166428:A:T	C64S	0.959
21:30166465:C:A	W51C	0.958
21:30166465:C:G	W51C	0.958
21:30166144:T:A	K158N	0.949
21:30166144:T:G	K158N	0.949
21:30166197:C:G	A141P	0.949
21:30166467:A:G	W51R	0.946
21:30166467:A:T	W51R	0.946

dbSNP variants (sampled 300 via entrez): RS1002013415 (21:30167772 G>A,T), RS1002247060 (21:30165219 C>A,T), RS1002913450 (21:30167564 G>A), RS1005188810 (21:30168387 A>G), RS1005273075 (21:30166205 C>T), RS1005535280 (21:30168677 C>T), RS1005877539 (21:30167200 G>A), RS1006607721 (21:30167245 A>G), RS1009006361 (21:30165670 T>C), RS1009058581 (21:30165512 A>C,G), RS1009407022 (21:30165227 T>A,C), RS1009657729 (21:30165458 A>G), RS1010069110 (21:30167856 G>A), RS1010121186 (21:30165256 T>A,C), RS1012807011 (21:30165978 T>C)

Disease associations

OMIM: gene MIM:617005 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000635_20	Response to statin therapy	8.000000e-06
GCST002987_14	Stroke	1.000000e-06
GCST002987_27	Stroke	1.000000e-06
GCST007326_84	Number of sexual partners	5.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	2
sodium arsenite	affects methylation	1
benzo(k)fluoranthene	decreases expression	1
benz(a)anthracene	decreases expression	1
indeno(1,2,3-cd)pyrene	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Fulvestrant	decreases methylation	1
Aerosols	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Methylcholanthrene	affects binding, increases reaction	1
Tetrachlorodibenzodioxin	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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