CLDN19

Summary

CLDN19 (claudin 19, HGNC:2040) is a protein-coding gene on chromosome 1p34.2, encoding Claudin-19 (Q8N6F1). Forms paracellular channels: coassembles with CLDN16 into tight junction strands with cation-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability.

The product of this gene belongs to the claudin family. It plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Defects in this gene are the cause of hypomagnesemia renal with ocular involvement (HOMGO). HOMGO is a progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 149461 — RefSeq curated summary.

At a glance

• Gene–disease (curated): renal hypomagnesemia 5 with ocular involvement (Definitive, GenCC)
• Clinical variants (ClinVar): 213 total — 8 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 29
• MANE Select transcript: NM_148960

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2040
Approved symbol	CLDN19
Name	claudin 19
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164007
Ensembl biotype	protein_coding
OMIM	610036
Entrez	149461

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000296387, ENST00000372539, ENST00000539749

RefSeq mRNA: 3 — MANE Select: NM_148960 NM_001123395, NM_001185117, NM_148960

CCDS: CCDS44125, CCDS471, CCDS53306

Canonical transcript exons

ENST00000296387 — 5 exons

Exon	Start	End
ENSE00001080455	42738229	42738313
ENSE00001080458	42738421	42738585
ENSE00001189798	42735878	42736030
ENSE00001277057	42733093	42735134
ENSE00003891358	42739841	42740236

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 98.54.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3951 / max 199.4628, expressed in 249 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11996	1.3405	243
11997	0.0546	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trigeminal ganglion	UBERON:0001675	98.54	gold quality
dorsal root ganglion	UBERON:0000044	98.14	gold quality
pigmented layer of retina	UBERON:0001782	96.66	gold quality
renal medulla	UBERON:0000362	96.64	gold quality
tibial nerve	UBERON:0001323	96.07	gold quality
vena cava	UBERON:0004087	93.37	gold quality
epithelium of nasopharynx	UBERON:0001951	89.42	silver quality
body of tongue	UBERON:0011876	89.35	silver quality
superficial temporal artery	UBERON:0001614	89.22	silver quality
tongue	UBERON:0001723	89.20	silver quality
ventral tegmental area	UBERON:0002691	88.99	silver quality
trachea	UBERON:0003126	88.97	silver quality
superior surface of tongue	UBERON:0007371	88.88	silver quality
pharyngeal mucosa	UBERON:0000355	88.35	silver quality
lateral globus pallidus	UBERON:0002476	88.18	silver quality
lateral nuclear group of thalamus	UBERON:0002736	87.97	silver quality
pericardium	UBERON:0002407	87.87	silver quality
decidua	UBERON:0002450	87.83	gold quality
medulla oblongata	UBERON:0001896	87.82	silver quality
mucosa of paranasal sinus	UBERON:0005030	87.80	silver quality
saphenous vein	UBERON:0007318	87.61	silver quality
pons	UBERON:0000988	87.58	silver quality
substantia nigra pars reticulata	UBERON:0001966	87.57	silver quality
nipple	UBERON:0002030	87.55	silver quality
cerebellar vermis	UBERON:0004720	86.19	gold quality
sural nerve	UBERON:0015488	86.13	gold quality
placenta	UBERON:0001987	85.13	gold quality
mammary duct	UBERON:0001765	84.73	gold quality
synovial joint	UBERON:0002217	84.57	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	158.98
E-MTAB-6701	yes	78.57
E-ANND-3	yes	2.62

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
BEST1	Activation
EGFR	Repression
FRZB	Activation
MYC	Repression
SFRP5	Activation
SLC38A11	Activation
TTR	Activation

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

47 targeting CLDN19, 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-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4270	99.02	66.26	1987

Literature-anchored findings (GeneRIF, showing 16)

• The identification of CLDN19 mutations in patients with chronic renal failure and severe visual impairment supports the fundamental role of claudin-19 for normal renal tubular function and undisturbed organization and development of the retina. (PMID:17033971)
• Ocular manifestations and exercise intolerance mimicking mild to moderate periodic paralysis are two symptoms that may occur in patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis and may indicate CLDN19 mutations. (PMID:21030577)
• The risk of end-stage renal disease in patients with CLDN19 mutations was two times the risk of patients with CLDN16 mutations. Ocular abnormalities were observed only in patients with CLDN19 mutations. (PMID:22422540)
• In a patient with consanguineous parents, history of disturbed organization and development of the retina, a diagnosis of Familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by claudin-19 mutation should be considered. (PMID:22734304)
• patients with CLDN19 mutations have a high risk of progression to chronic renal disease (PMID:23301036)
• Case Reports: novel CLDN19 mutation in familial hypomagnesemia with hypercalciuria and nephrocalcinosis. (PMID:23538362)
• CLDN19 genetic mutation is responsible for familial magnesium deficiency with hypercalciuria and nephrocalcinosis. (PMID:25410674)
• analysis of a novel mutation c.241C>T in exon 2 of CLDN19 in a Chinese patient (PMID:25555744)
• Claudin-19, the most abundant claudin in myelin, exhibited no binding to ZO2 protein. (PMID:25712527)
• permeability barriers and affected cell morphology, proliferation, migration, AKT signaling, and gene expression. When claudins are exogenously expressed, ARPE-19 more closely model native RPE. (PMID:27593915)
• Homozygous CLDN19 mutation is associated with Familial non-syndromic macular pseudocoloboma. (PMID:30067419)
• No significant associations were found among claudin-16 and claudin-19 single-nucleotide polymorphisms and calcium excretion and between claudin-14, claudin-16, and claudin-19 single-nucleotide polymorphisms and stones. (PMID:30232134)
• Results show that CLDN16 mutation c.602G>A had no effect on pre-mRNA splicing in familial hypomagnesemia with hypercalciuria and nephrocalcinosis. This study expands the genotypic classification of this rare disease and provides the first report of a CLDN19 mutation affecting splicing. (PMID:30576809)
• Mutated claudin-19 affects multiple stages of RPE and retinal differentiation through its effects on multiple functions of the RPE. (PMID:30937396)
• Knockdown of Claudin-19 in the Retinal Pigment Epithelium Is Accompanied by Slowed Phagocytosis and Increased Expression of SQSTM1. (PMID:33591357)
• Heterogeneity is a common ground in familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by CLDN19 gene mutations. (PMID:33929692)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cldn19	ENSDARG00000044569
mus_musculus	Cldn19	ENSMUSG00000066058
rattus_norvegicus	Cldn19	ENSRNOG00000007922

Paralogs (22): CLDN11 (ENSG00000013297), CLDN18 (ENSG00000066405), CLDN15 (ENSG00000106404), CLDN16 (ENSG00000113946), CLDN10 (ENSG00000134873), CLDN17 (ENSG00000156282), CLDN8 (ENSG00000156284), CLDN14 (ENSG00000159261), CLDN1 (ENSG00000163347), 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-19 — Q8N6F1 (reviewed: Q8N6F1)

All UniProt accessions (1): Q8N6F1

UniProt curated annotations — full annotation on UniProt →

Function. Forms paracellular channels: coassembles with CLDN16 into tight junction strands with cation-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability. Involved in the maintenance of ion gradients along the nephron. In the thick ascending limb (TAL) of Henle’s loop, facilitates sodium paracellular permeability from the interstitial compartment to the lumen, contributing to the lumen-positive transepithelial potential that drives paracellular magnesium and calcium reabsorption. Forms paracellular barriers on its own. In the peripheral nervous system, represents a major constituent of the tight junctions in Schwann cells and contributes to electrical sealing. During retinal neurogenesis, may regulate the barrier properties of tight junctions in retinal pigment epithelium, required for proper retinal tissue differentiation and vision.

Subunit / interactions. Can form homo- and heteropolymeric tight junction strands. Interacts with other claudins including CLDN3, CLDN10, CLDN16 and CLDN18 with highest affinity for CLDN16. Interacts (via PDZ-binding motif TRV) with TJP1 (via PDZ domain).

Subcellular location. Cell junction. Tight junction. Cell membrane.

Disease relevance. Hypomagnesemia 5, renal, with or without ocular involvement (HOMG5) [MIM:248190] A progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus. The renal phenotype is virtually undistinguishable from that of patients with HOMG3. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the claudin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N6F1-1	1	yes
Q8N6F1-2	2
Q8N6F1-3	3

RefSeq proteins (3): NP_001116867, NP_001172046, NP_683763* (*=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:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Mg(2+)(in) = Mg(2+)(out) (RHEA:29827)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• Rb(+)(in) = Rb(+)(out) (RHEA:78547)
• Li(+)(in) = Li(+)(out) (RHEA:78551)
• Cs(+)(in) = Cs(+)(out) (RHEA:78555)

UniProt features (22 total): sequence variant 6, topological domain 5, transmembrane region 4, splice variant 2, sequence conflict 2, chain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6F1-F1	81.08	0.46

Functional residue map

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

Disulfide bonds (1): 54–64

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions

MSigDB gene sets: 180 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_APICAL_JUNCTION_ASSEMBLY, KEGG_TIGHT_JUNCTION, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION, RGTTAMWNATT_HNF1_01, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_TRANSEPITHELIAL_TRANSPORT, chr1p34, GOBP_SENSORY_PERCEPTION, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_CELL_CELL_JUNCTION_ASSEMBLY, GOBP_RENAL_ABSORPTION

GO Biological Process (17): retinal pigment epithelium development (GO:0003406), cell adhesion (GO:0007155), visual perception (GO:0007601), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), calcium-independent cell-cell adhesion (GO:0016338), neuronal action potential propagation (GO:0019227), actin cytoskeleton organization (GO:0030036), negative regulation of cell migration (GO:0030336), cell junction assembly (GO:0034329), renal absorption (GO:0070293), bicellular tight junction assembly (GO:0070830), regulation of transepithelial transport (GO:0150111), paracellular transport (GO:0160184), apical junction assembly (GO:0043297), tight junction organization (GO:0120193)

GO Molecular Function (5): structural molecule activity (GO:0005198), identical protein binding (GO:0042802), cell-cell adhesion mediator activity (GO:0098632), paracellular tight junction channel activity (GO:0160187), protein binding (GO:0005515)

GO Cellular Component (14): nucleus (GO:0005634), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), basolateral plasma membrane (GO:0016323), paranodal junction (GO:0033010), Schmidt-Lanterman incisure (GO:0043220), apical junction complex (GO:0043296), perinuclear region of cytoplasm (GO:0048471), tight junction (GO:0070160), mesaxon (GO:0097453), cytoplasm (GO:0005737), membrane (GO:0016020), cell junction (GO:0030054), 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
cellular anatomical structure	5
cell-cell junction	3
gene expression	2
regulation of gene expression	2
cell-cell adhesion	2
retina development in camera-type eye	1
epithelium development	1
cellular process	1
sensory perception of light stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
transmission of nerve impulse	1
nervous system process	1
action potential propagation	1
cytoskeleton organization	1
actin filament-based process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
cellular component assembly	1
cell junction organization	1
renal system process	1
apical junction assembly	1
tight junction assembly	1
regulation of transport	1
transepithelial transport	1
transport	1
cell-cell junction assembly	1
cell-cell junction organization	1
molecular_function	1
protein binding	1
cell adhesion mediator activity	1
transporter activity	1
binding	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

777 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN19	CLDN16	Q9Y5I7	972
CLDN19	TJP1	Q07157	868
CLDN19	FXYD2	P54710	853
CLDN19	TRPM6	Q9BX84	809
CLDN19	CLDN12	P56749	633
CLDN19	PTH	P01270	626
CLDN19	OCLN	Q16625	614
CLDN19	CLDN3	O15551	610
CLDN19	TRPM7	Q96QT4	610
CLDN19	CNNM2	Q9H8M5	583
CLDN19	CLCNKB	P51801	580
CLDN19	CASR	P41180	571
CLDN19	SLC41A1	Q8IVJ1	547
CLDN19	KCNJ1	P48048	545
CLDN19	SLC12A1	Q13621	526

IntAct

135 interactions, top by confidence:

A	B	Type	Score
CLDN19	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CLDN19	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	PTPN13	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	RAPGEF6	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	DLG5	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	LIN7B	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	DVL3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN19	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (67): CREB3 (Two-hybrid), PKD2L1 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid), CLDN19 (Two-hybrid)

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	50.1×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	47.7×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	47.7×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	44.5×	1e-12
Dopamine Neurotransmitter Release Cycle	5	43.5×	2e-06
Long-term potentiation	5	41.7×	3e-06
Neurexins and neuroligins	11	38.0×	7e-13
Protein-protein interactions at synapses	7	32.6×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	77.0×	4e-16
protein localization to synapse	6	55.4×	1e-07
receptor clustering	7	52.6×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	41.8×	5e-08
bicellular tight junction assembly	5	19.9×	2e-04
protein-containing complex assembly	9	12.3×	3e-06
cell-cell adhesion	10	12.2×	7e-07
regulation of small GTPase mediated signal transduction	5	8.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	14
Uncertain significance	113
Likely benign	50
Benign	14

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1333609	NM_148960.3(CLDN19):c.427del (p.Leu143fs)	Pathogenic
1362	NM_148960.3(CLDN19):c.169C>G (p.Gln57Glu)	Pathogenic
1363	NM_148960.3(CLDN19):c.269T>C (p.Leu90Pro)	Pathogenic
1687613	NM_148960.3(CLDN19):c.474-1G>C	Pathogenic
2501010	NM_148960.3(CLDN19):c.181C>T (p.Gln61Ter)	Pathogenic
2747879	NM_148960.3(CLDN19):c.201C>A (p.Tyr67Ter)	Pathogenic
548637	NM_148960.3(CLDN19):c.169C>T (p.Gln57Ter)	Pathogenic
560599	NM_148960.3(CLDN19):c.388G>T (p.Gly130Cys)	Pathogenic
1333489	NM_148960.3(CLDN19):c.83C>T (p.Pro28Leu)	Likely pathogenic
2119983	NM_148960.3(CLDN19):c.474-1G>A	Likely pathogenic
3068324	NM_148960.3(CLDN19):c.162C>A (p.Cys54Ter)	Likely pathogenic
3242162	NM_148960.3(CLDN19):c.535G>C (p.Gly179Arg)	Likely pathogenic
3384045	NM_148960.3(CLDN19):c.263T>A (p.Val88Glu)	Likely pathogenic
3384048	NM_148960.3(CLDN19):c.241C>T (p.Arg81Trp)	Likely pathogenic
3583940	NM_148960.3(CLDN19):c.263_270dup (p.Gly91fs)	Likely pathogenic
3583944	NM_148960.3(CLDN19):c.223+1G>A	Likely pathogenic
3583947	NM_148960.3(CLDN19):c.178_182delinsCCC (p.Gly60fs)	Likely pathogenic
3583982	NM_148960.3(CLDN19):c.140_141del (p.Leu46_Tyr47insTer)	Likely pathogenic
3777110	NM_148960.3(CLDN19):c.223G>C (p.Gly75Arg)	Likely pathogenic
4074278	NM_148960.3(CLDN19):c.392T>G (p.Leu131Arg)	Likely pathogenic
4294299	NM_148960.3(CLDN19):c.220del (p.Asp74fs)	Likely pathogenic
974422	NM_148960.3(CLDN19):c.530T>G (p.Leu177Arg)	Likely pathogenic

SpliceAI

591 predictions. Top by Δscore:

Variant	Effect	Δscore
1:42736604:C:A	donor_gain	1.0000
1:42738224:CCCA:C	donor_loss	1.0000
1:42738226:CACCT:C	donor_loss	1.0000
1:42738227:ACC:A	donor_loss	1.0000
1:42738309:GAGGC:G	acceptor_gain	1.0000
1:42738311:GGC:G	acceptor_gain	1.0000
1:42738311:GGCC:G	acceptor_loss	1.0000
1:42738312:GC:G	acceptor_gain	1.0000
1:42738312:GCCTA:G	acceptor_loss	1.0000
1:42738313:CC:C	acceptor_gain	1.0000
1:42738314:C:CC	acceptor_gain	1.0000
1:42738314:C:CG	acceptor_loss	1.0000
1:42738314:C:T	acceptor_gain	1.0000
1:42738315:T:G	acceptor_loss	1.0000
1:42738416:CTCA:C	donor_loss	1.0000
1:42738418:CACC:C	donor_loss	1.0000
1:42738419:A:AC	donor_gain	1.0000
1:42738420:C:CC	donor_gain	1.0000
1:42738420:C:CT	donor_loss	1.0000
1:42739835:GCCTA:G	donor_loss	1.0000
1:42739836:CCTAC:C	donor_loss	1.0000
1:42739838:TA:T	donor_loss	1.0000
1:42739839:A:AT	donor_loss	1.0000
1:42739840:C:CA	donor_loss	1.0000
1:42735876:A:AC	donor_gain	0.9900
1:42735877:C:CC	donor_gain	0.9900
1:42735877:CT:C	donor_gain	0.9900
1:42736026:CATAC:C	acceptor_gain	0.9900
1:42736028:TAC:T	acceptor_gain	0.9900
1:42736030:CCTG:C	acceptor_loss	0.9900

AlphaMissense

1413 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:42739873:C:G	C64S	1.000
1:42739874:A:T	C64S	1.000
1:42739974:C:A	W30C	1.000
1:42739974:C:G	W30C	1.000
1:42735999:A:G	W169R	0.999
1:42735999:A:T	W169R	0.999
1:42736019:C:A	G162V	0.999
1:42736019:C:T	G162D	0.999
1:42738258:G:C	F148L	0.999
1:42738258:G:T	F148L	0.999
1:42738260:A:G	F148L	0.999
1:42739874:A:G	C64R	0.999
1:42739903:C:T	C54Y	0.999
1:42739911:C:A	W51C	0.999
1:42739911:C:G	W51C	0.999
1:42739913:A:G	W51R	0.999
1:42739913:A:T	W51R	0.999
1:42739918:C:T	G49E	0.999
1:42739919:C:A	G49W	0.999
1:42739919:C:G	G49R	0.999
1:42739919:C:T	G49R	0.999
1:42739976:A:G	W30R	0.999
1:42739976:A:T	W30R	0.999
1:42740006:C:G	G20R	0.999
1:42735968:C:T	G179D	0.998
1:42735969:C:G	G179R	0.998
1:42735971:C:T	G178D	0.998
1:42735972:C:G	G178R	0.998
1:42736001:C:T	G168D	0.998
1:42736002:C:G	G168R	0.998

dbSNP variants (sampled 300 via entrez): RS1000192988 (1:42733339 G>A), RS1000254006 (1:42737722 A>G), RS1000309581 (1:42737428 G>A), RS1000414286 (1:42732845 C>G), RS1000530698 (1:42734547 C>T), RS1000749435 (1:42734293 T>C), RS1000775945 (1:42738873 C>T), RS1001149177 (1:42738932 T>C), RS1001158726 (1:42739247 T>C,G), RS1001193331 (1:42736251 G>A), RS1001707873 (1:42733723 G>GGACA), RS1001800620 (1:42738315 T>C), RS1002138865 (1:42733988 A>T), RS1002446383 (1:42734952 C>T), RS1002805551 (1:42739530 G>A,T)

Disease associations

OMIM: gene MIM:610036 | disease phenotypes: MIM:248190

GenCC curated gene-disease

Disease	Classification	Inheritance
renal hypomagnesemia 5 with ocular involvement	Definitive	Autosomal recessive

Mondo (3): renal hypomagnesemia 5 with ocular involvement (MONDO:0009548), nephrocalcinosis (MONDO:0001567), nephrolithiasis (MONDO:0008171)

Orphanet (1): Primary hypomagnesemia with hypercalciuria and nephrocalcinosis with severe ocular involvement (Orphanet:2196)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000112	Nephropathy
HP:0000121	Nephrocalcinosis
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000510	Rod-cone dystrophy
HP:0000545	Myopia
HP:0000567	Chorioretinal coloboma
HP:0000639	Nystagmus
HP:0000705	Amelogenesis imperfecta
HP:0000787	Nephrolithiasis
HP:0000790	Hematuria
HP:0001116	Macular pseudocoloboma
HP:0001537	Umbilical hernia
HP:0002150	Hypercalciuria
HP:0002917	Hypomagnesemia
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003774	Stage 5 chronic kidney disease
HP:0004363	Abnormal circulating calcium concentration
HP:0005567	Renal magnesium wasting
HP:0007703	Abnormal retinal pigmentation
HP:0011463	Childhood onset
HP:0012608	Hypermagnesiuria
HP:0012622	Chronic kidney disease
HP:0012637	Renal calcium wasting
HP:0100530	Abnormal circulating calcium-phosphate regulating hormone concentration

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009397	Nephrocalcinosis	C12.050.351.968.419.590; C12.200.777.419.590; C12.950.419.590; C18.452.174.130.560
D053040	Nephrolithiasis	C12.050.351.968.419.600; C12.050.351.968.967.249; C12.200.777.419.600; C12.200.777.967.249; C12.950.419.600; C12.950.967.249
C536148	Meier Blumberg Imahorn syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	4
bisphenol A	affects expression	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
avobenzone	decreases expression	1
licochalcone B	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Parathion	increases methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Tetrachlorodibenzodioxin	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00765128	PHASE4	COMPLETED	Intravenous Ketorolac for Postoperative Pain in Percutaneous Nephrolithotomy
NCT01295879	PHASE4	COMPLETED	Vitamin D Repletion in Stone Formers With Hypercalciuria
NCT01329042	PHASE4	COMPLETED	Efficacy of Potassium Sodium Hydrogen Citrate Therapy on Renal Stone Recurrence and/or Residual Fragments After Shockwave Lithotripsy and Percutaneous Nephrolithotomy in Calcium Oxalate Urolithiasis
NCT01452880	PHASE4	COMPLETED	Remifentanil in Extracorporeal Shock Wave Lithotripsy
NCT01675362	PHASE4	COMPLETED	Are There Protective Effects of Antioxidants, Calcium Channel Blocker and Angiotensin Receptor Blocker Against Extracorporeal Shockwaves Lithotripsy Induced Renal Injury?
NCT02011737	PHASE4	UNKNOWN	Naftopidil 75mg for Improving Clearance of Urinary Stones
NCT02095665	PHASE4	COMPLETED	Ureteral Stent-related Pain and Mirabegron (SPAM) Trial
NCT02375295	PHASE4	UNKNOWN	Struvite Stones Antibiotic Study
NCT02384200	PHASE4	COMPLETED	A Randomized Trial of Preoperative Prophylactic Antibiotics Prior to Kidney Stone Surgery (Percutaneous Nephrolithotomy [PCNL])
NCT02430168	PHASE4	UNKNOWN	Comparison of RIRS Versus PCNL Methods, According to Postoperative Pain and Analgesic Demand in 2 to 4 cm Renal Stones
NCT02430883	PHASE4	UNKNOWN	Is There Any Relation Between Pain and Stone Location in Retrograde Intrarenal Surgery?
NCT02443909	PHASE4	UNKNOWN	Comparison of Safety and Efficiency of 20w and 30w Holmium Laser Device in Management of 2-3 cm Diameter Kidney Stones With Retrograde Intrarenal Surgery
NCT02451319	PHASE4	UNKNOWN	Comparison of Safety and Efficiency of 20w 30w Holmium Laser Device in Treatment of 1-2 cm Diameter Kidney Stones With RIRS
NCT02489656	PHASE4	UNKNOWN	Quality of Life in Patients With Double Loop Ureteral Stent (JJ Silicone Hydrogel Study)
NCT02818140	PHASE4	COMPLETED	Ultrasound-guided Transmuscular Quadratus Lumborum Block for Percutaneous Nephrolithotomy
NCT02966236	PHASE4	UNKNOWN	Impact of Tranexamic Acid Use in Percutaneous Nephrolithotomy
NCT03035812	PHASE4	COMPLETED	Alkalinization by Urologists & Nephrologists
NCT03229889	PHASE4	COMPLETED	Trial of Tadalafil, Tamsulosin and Combination for Access Sheath Deployment
NCT03332056	PHASE4	COMPLETED	The Use of Belladonna and Opium Suppository in the Treatment of Postoperative Stent Pain
NCT03549611	PHASE4	WITHDRAWN	Pre-induction Analgesia: Multimodel Regimen vs Aceteminophen for Post Ureteroscopy Pain
NCT03692715	PHASE4	COMPLETED	Antibiotic Prophylaxis Before Shock Wave Lithotripsy
NCT03872843	PHASE4	COMPLETED	Opioid Free Management After Ureteroscopy
NCT03888144	PHASE4	COMPLETED	Study of Ketorolac Versus Opioid for Pain After Endoscopy
NCT04095975	PHASE4	COMPLETED	Effectiveness of Urinary Alkalinizing Agents on Kidney Stone Risk
NCT04663269	PHASE4	TERMINATED	Regional Erector Spinae Analgesic Block vs Standard of Care Undergoing Percutaneous Nephrolithotomy
NCT05082142	PHASE4	COMPLETED	Tranexamic Acid to Improve Same-day Discharge Rates After Holmium Laser Enucleation of the Prostate (HoLEP)
NCT05365477	PHASE4	COMPLETED	Empiric Versus Selective Prevention Strategies for Kidney Stone Disease
NCT05414669	PHASE4	COMPLETED	Allopurinol Effect on MDA,NO,KIM-1 Urine Levels, RI and Renal Elastography in Kidney Stone Patients Post ESWL
NCT05924165	PHASE4	COMPLETED	Narcotic-Free Percutaneous Nephrolithotomy
NCT06124066	PHASE4	COMPLETED	THE EFFECTS OF MIRABEGRON AND TAMSULOSIN FOR PATIENTS WITH URETERAL STENTS
NCT06966635	PHASE4	RECRUITING	Exploratory Study on the Treatment of Gout With Potassium Citrate Sustained-release Tablets
NCT07124299	PHASE4	RECRUITING	Alpha-Blockers Prior to Ureteral Access Sheath Placement in Flexible Ureteroscopy: A Randomized Prospective Study
NCT07225764	PHASE4	RECRUITING	CaOx Stone Prevention
NCT07512297	PHASE4	NOT_YET_RECRUITING	Pain Control During ESWL Using Non-Opioid Analgesics
NCT07582341	PHASE4	COMPLETED	Combined Intravenous and Irrigation Tranexamic Acid During Percutaneous Nephrolithotomy
NCT00249951	PHASE3	COMPLETED	Alkaline Citrate Treatment to Lower the Risk of Nephrocalcinosis in Preterm Infants
NCT01756547	PHASE3	UNKNOWN	Study to Assess the Efficacy and Safety of Oral Potassium Citrate on the Prevention of Nephrocalcinosis in Extreme Premature
NCT00004284	PHASE3	COMPLETED	Phase III Randomized, Double-Blind Study of Potassium Phosphate Vs Potassium Citrate for Absorptive Hypercalciuria
NCT00177086	PHASE3	COMPLETED	Alfuzosin Hydrochloride to Promote Passage of Distal Ureteral Calculi
NCT00713739	PHASE3	UNKNOWN	Alfuzosin for Medical Expulsion Therapy of Ureteral Stones