CLDN10

Summary

CLDN10 (claudin 10, HGNC:2033) is a protein-coding gene on chromosome 13q32.1, encoding Claudin-10 (P78369). Forms paracellular channels: polymerizes in tight junction strands with cation- and anion-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability.

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. The expression level of this gene is associated with recurrence of primary hepatocellular carcinoma. Six alternatively spliced transcript variants encoding different isoforms have been reported, but the transcript sequences of some variants are not determined.

Source: NCBI Gene 9071 — RefSeq curated summary.

At a glance

• Gene–disease (curated): HELIX syndrome (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 57 total — 6 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 16
• MANE Select transcript: NM_006984

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2033
Approved symbol	CLDN10
Name	claudin 10
Location	13q32.1
Locus type	gene with protein product
Status	Approved
Aliases	OSP-L, CPETRL3
Ensembl gene	ENSG00000134873
Ensembl biotype	protein_coding
OMIM	617579
Entrez	9071

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000299339, ENST00000376855, ENST00000376873, ENST00000905060

RefSeq mRNA: 3 — MANE Select: NM_006984 NM_001160100, NM_006984, NM_182848

CCDS: CCDS9475, CCDS9476

Canonical transcript exons

ENST00000299339 — 5 exons

Exon	Start	End
ENSE00000853813	95577231	95577338
ENSE00000853814	95560382	95560463
ENSE00000853815	95560132	95560293
ENSE00001128319	95552720	95552973
ENSE00001353009	95577900	95579759

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 99.00.

FANTOM5 (CAGE): breadth broad, TPM avg 5.8845 / max 362.1460, expressed in 378 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135688	5.4282	365
135687	0.3871	175
135685	0.0192	4
135680	0.0126	3
135682	0.0121	4
135686	0.0114	7
135681	0.0072	3
135683	0.0039	2
135684	0.0028	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.00	gold quality
pancreatic ductal cell	CL:0002079	98.47	gold quality
body of pancreas	UBERON:0001150	97.77	gold quality
nephron tubule	UBERON:0001231	96.87	gold quality
adult organism	UBERON:0007023	93.96	gold quality
pancreas	UBERON:0001264	93.58	gold quality
adult mammalian kidney	UBERON:0000082	93.51	gold quality
kidney epithelium	UBERON:0004819	93.08	gold quality
epithelial cell of pancreas	CL:0000083	93.04	gold quality
epithelium of nasopharynx	UBERON:0001951	92.03	gold quality
nasopharynx	UBERON:0001728	92.01	gold quality
metanephros cortex	UBERON:0010533	91.84	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.73	gold quality
gall bladder	UBERON:0002110	91.40	gold quality
renal medulla	UBERON:0000362	91.17	gold quality
kidney	UBERON:0002113	91.02	gold quality
caput epididymis	UBERON:0004358	90.60	gold quality
corpus epididymis	UBERON:0004359	90.45	gold quality
amygdala	UBERON:0001876	90.27	gold quality
right uterine tube	UBERON:0001302	89.62	gold quality
upper leg skin	UBERON:0004262	89.20	gold quality
renal glomerulus	UBERON:0000074	89.04	gold quality
metanephric glomerulus	UBERON:0004736	88.96	gold quality
bronchial epithelial cell	CL:0002328	88.89	gold quality
saliva-secreting gland	UBERON:0001044	88.28	gold quality
tonsil	UBERON:0002372	88.13	gold quality
temporal lobe	UBERON:0001871	88.08	gold quality
nasal cavity mucosa	UBERON:0001826	88.05	gold quality
epithelium of bronchus	UBERON:0002031	88.03	gold quality
bronchus	UBERON:0002185	88.00	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	3141.69
E-GEOD-130473	yes	1111.04
E-MTAB-3929	yes	1092.33
E-MTAB-8495	yes	760.70
E-GEOD-114530	yes	698.65
E-MTAB-10287	yes	49.41
E-MTAB-5061	yes	28.39
E-MTAB-10553	yes	26.94
E-HCAD-6	yes	24.56
E-MTAB-6701	yes	15.40
E-GEOD-84465	yes	13.75
E-GEOD-83139	yes	13.66
E-HCAD-10	yes	12.73
E-HCAD-9	yes	11.70
E-HCAD-1	yes	11.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting CLDN10, 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-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-105-5P	99.54	69.24	2060

Literature-anchored findings (GeneRIF, showing 18)

• High Claudin-10 expression level is associated with recurrence of primary hepatocellular carcinoma (PMID:15701840)
• These findings showed that CLDN-10 is functionally involved in hepatocellular carcinoma invasion and is a potential target for hepatocellular carcinoma therapy. (PMID:18025272)
• Claudin-10 exists in six alternatively spliced isoforms that exhibit distinct localization and function. (PMID:19383724)
• CLDN10 is a novel biomarker for detecting ovarian cancer in the chicken, a suitable animal model for investigating the effect and function of CLDN in human ovarian cancer. (PMID:21370593)
• Claudin 10 protein is highly expressed in hepatocellular carcinoma (HCC) tissue and is closely related to angiogenesis. It could be a useful marker to predict poor prognosis of HCC patients after hepatectomy. (PMID:21647678)
• Claudin 10/18 are most commonly expressed in lung adenocarcinomas. Female patients and non-smokers express these claudins more commonly suggesting that they may play a part in the carcinogenesis of tobacco unrelated carcinoma. (PMID:22076167)
• Expression of CLDN1 and CLDN10 was lower in invasive lepidic predominant adenocarcinoma than in lung adenocarcioma in situ. Overexpression of CLDN1 and CLDN10 indicates a favorable prognosis in some patients with lung adenocarcinoma. (PMID:23591077)
• In claudin-10b, the F66L mutant reduced cation selectivity, and the F66A mutant lost pore conductance (PMID:23760508)
• Claudin 10 expression was down-regulated in gastric cancer. (PMID:24325792)
• An algorithm combining CLDN10, HMGA2, and LAMB3 transcripts was able to discriminate tumors from BTL samples (94% sensitivity and 96% specificity in validation set). (PMID:25867809)
• localization of Cldn3, Cldn7 and Cldn10 proteins in the different compartments of murine endometrium up to day 8.5 of pregnancy (dpc) as well as in human endometrium and first trimester decidua (PMID:26340953)
• These renal-derived features recapitulate several phenotypic aspects detected in mice with kidney specific loss of both claudin-10 isoforms. Our study adds to the spectrum of phenotypes caused by tight junction proteins and demonstrates a pivotal role for claudin-10b in maintaining paracellular Na+ permeability for sweat production and kidney function. (PMID:28686597)
• The CLDN10 polymorphism of rs1325774 was significantly associated with an increased risk of breast cancer. After adjusting for age, the association remained statically significant. Furthermore, harbouring G allele in rs1325774 position was significantly associated with increased risk of breast cancer. However, no significant association among rs7333503, rs3751334, and breast cancer. (PMID:30544377)
• Study describes a novel claudinopathy that is based on mutations in the CLDN10 gene and characterized by an impaired function of mainly claudin-10b. Patients show a salt-losing nephropathy without hypercalciuria, and the severity of clinical manifestations may depend on site and type of mutation. [review] (PMID:31671507)
• Immune-related key gene CLDN10 correlates with lymph node metastasis but predicts favorable prognosis in papillary thyroid carcinoma. (PMID:32045884)
• A novel claudin-10 mutation with a unique mechanism in two unrelated families with HELIX syndrome. (PMID:33675844)
• Claudin-10 overexpression suppresses human clear cell renal cell carcinoma growth and metastasis by regulating ATP5O and causing mitochondrial dysfunction. (PMID:35414767)
• Impact of claudin-10 deficiency on amelogenesis: Lesson from a HELIX tooth. (PMID:35902997)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cldn10d	ENSDARG00000058906
danio_rerio	cldn10a	ENSDARG00000058937
danio_rerio		ENSDARG00000099598
danio_rerio	cldn10b	ENSDARG00000104528
mus_musculus	Cldn10	ENSMUSG00000022132
rattus_norvegicus	Cldn10	ENSRNOG00000010085

Paralogs (22): CLDN11 (ENSG00000013297), CLDN18 (ENSG00000066405), CLDN15 (ENSG00000106404), CLDN16 (ENSG00000113946), CLDN17 (ENSG00000156282), 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-10 — P78369 (reviewed: P78369)

Alternative names: Oligodendrocyte-specific protein-like

All UniProt accessions (2): P78369, Q5W075

UniProt curated annotations — full annotation on UniProt →

Function. Forms paracellular channels: polymerizes in tight junction strands with cation- and anion-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability. Forms cation-selective paracellular channels. In sweat glands and in the thick ascending limb (TAL) of Henle’s loop in kidney, it controls paracellular sodium permeability which is essential for proper sweat production and renal function. Forms anion-selective paracellular channels. In renal proximal tubules, it conveys selective chloride over hydrogencarbonate anion permeability which is required for renal chloride reabsorption and salt homeostasis.

Subunit / interactions. Can form homodimers both in trans (interaction between CLDN10 molecules in opposing membranes) and in cis (interaction between CLDN10 molecules within one membrane). Interacts with CLDN19. Interacts with CLDN19.

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

Tissue specificity. Expressed in the kidney, eccrine sweat glands and in all layers of the epidermis. In the kidney, it is detected in the thick ascending limb of Henle’s loop (TAL). In the sweat glands, it is expressed in cells from secretory portions, corresponding to the clear cells.

Disease relevance. HELIX syndrome (HELIX) [MIM:617671] An autosomal recessive disease characterized by congenital heat intolerance, generalized anhidrosis, inability to produce tears, dry mouth, electrolyte imbalance, and ichthyosis. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The fourth transmembrane region (161-181) is necessary for integration into tight junctions.

Miscellaneous. Produced by alternative splicing of isoform 2.

Similarity. Belongs to the claudin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P78369-1	1, Cldn10b	yes
P78369-2	2, Cldn10a
P78369-3	3, Cldn10a_i1

RefSeq proteins (3): NP_001153572, NP_008915, NP_878268 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003554	Claudin10	Family
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR006187	Claudin	Family
IPR017974	Claudin_CS	Conserved_site

Pfam: PF00822

Catalyzed reactions (Rhea), 12 shown:

• NH4(+)(in) = NH4(+)(out) (RHEA:28747)
• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• chloride(in) = chloride(out) (RHEA:29823)
• Mg(2+)(in) = Mg(2+)(out) (RHEA:29827)
• nitrate(in) = nitrate(out) (RHEA:34923)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• methylamine(out) = methylamine(in) (RHEA:74391)
• Rb(+)(in) = Rb(+)(out) (RHEA:78547)
• Li(+)(in) = Li(+)(out) (RHEA:78551)
• Cs(+)(in) = Cs(+)(out) (RHEA:78555)
• Sr(2+)(in) = Sr(2+)(out) (RHEA:78679)

UniProt features (15 total): transmembrane region 4, topological domain 4, splice variant 2, sequence variant 2, mutagenesis site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78369-F1	79.61	0.50

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 (2):

Position	Phenotype
36	no effect on tight junction strand formation and ion selectivity.
64	hinders formation of tight junction strands. a small fraction of these mutants is integrated into tight junction network

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells

MSigDB gene sets: 222 (showing top): GRUETZMANN_PANCREATIC_CANCER_DN, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, MODULE_64, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, KEGG_TIGHT_JUNCTION, HNF1_Q6, TTGCWCAAY_CEBPB_02, MODULE_66, GOBP_CELL_CELL_ADHESION, MARTINEZ_RB1_TARGETS_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, KOYAMA_SEMA3B_TARGETS_UP, NF1_Q6_01, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, HNF4_DR1_Q3

GO Biological Process (6): monoatomic ion transport (GO:0006811), cell adhesion (GO:0007155), calcium-independent cell-cell adhesion (GO:0016338), regulation of monoatomic ion transport (GO:0043269), bicellular tight junction assembly (GO:0070830), paracellular transport (GO:0160184)

GO Molecular Function (4): structural molecule activity (GO:0005198), identical protein binding (GO:0042802), paracellular tight junction channel activity (GO:0160187), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), tight junction (GO:0070160), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cell-cell junction organization	1
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
cellular anatomical structure	2
cellular process	1
cell-cell adhesion	1
monoatomic ion transport	1
regulation of transport	1
apical junction assembly	1
tight junction assembly	1
molecular_function	1
protein binding	1
transporter activity	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
cell-cell junction	1
cell junction	1

Protein interactions and networks

STRING

1064 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN10	CLDN12	P56749	634
CLDN10	EPCAM	P16422	493
CLDN10	CLDN23	Q96B33	491
CLDN10	OCLN	Q16625	489
CLDN10	TJP1	Q07157	482
CLDN10	CLDN16	Q9Y5I7	444
CLDN10	CLDN8	P56748	437
CLDN10	PATJ	Q8NI35	432
CLDN10	TJP2	Q9UDY2	432
CLDN10	TJP3	O95049	429
CLDN10	F11R	Q9Y624	421
CLDN10	ELF5	Q9UKW6	419
CLDN10	CDH6	P55285	417
CLDN10	WNK4	Q96J92	415
CLDN10	EOMES	O95936	394
CLDN10	CLIC6	Q96NY7	394

IntAct

148 interactions, top by confidence:

A	B	Type	Score
CLDN10	GOPC	psi-mi:“MI:0407”(direct interaction)	0.590
CLDN10	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
OPRM1	CLDN10	psi-mi:“MI:0915”(physical association)	0.560
CLDN10	CISD2	psi-mi:“MI:0915”(physical association)	0.560
PEX12	CLDN10	psi-mi:“MI:0915”(physical association)	0.560
CLDN10	TMEM9	psi-mi:“MI:0915”(physical association)	0.560
CLDN10	REEP1	psi-mi:“MI:0915”(physical association)	0.560
CLDN10	BEST2	psi-mi:“MI:0915”(physical association)	0.560
CLDN10	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
CLDN10	ATE1	psi-mi:“MI:0914”(association)	0.530
CLDN10	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	CLDN10	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	LNX1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
GIPC2	CLDN10	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	GRIP1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN10	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
PALS2	CLDN10	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (28): ATE1 (Affinity Capture-MS), FGF1 (Affinity Capture-MS), FGF1 (Affinity Capture-MS), ATE1 (Affinity Capture-MS), CLDN10 (Two-hybrid), CLDN10 (Two-hybrid), CLDN10 (Two-hybrid), CLDN10 (Two-hybrid), CLDN10 (Two-hybrid), CLDN10 (Two-hybrid), TMEM14B (Two-hybrid), CISD2 (Two-hybrid), HSD17B13 (Two-hybrid), CLDN10 (Proximity Label-MS), CLDN10 (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 86 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	49.2×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	46.9×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	46.9×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	43.8×	2e-12
Dopamine Neurotransmitter Release Cycle	5	42.8×	3e-06
Long-term potentiation	5	41.0×	3e-06
Neurexins and neuroligins	11	37.3×	9e-13
Protein-protein interactions at synapses	7	32.0×	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	6	35.8×	2e-06
protein-containing complex assembly	9	12.3×	4e-06
cell-cell adhesion	9	11.0×	7e-06
chemical synaptic transmission	8	7.5×	6e-04
protein transport	9	4.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	32
Likely benign	0
Benign	11

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1077192	Single allele	Pathogenic
2574668	NM_006984.5(CLDN10):c.138G>A (p.Trp46Ter)	Pathogenic
3338383	NM_006984.5(CLDN10):c.497G>A (p.Trp166Ter)	Pathogenic
438636	NM_006984.5(CLDN10):c.144C>G (p.Asn48Lys)	Pathogenic
438637	NM_006984.5(CLDN10):c.392C>T (p.Ser131Leu)	Pathogenic
438638	NM_006984.5(CLDN10):c.2T>C (p.Met1Thr)	Pathogenic
3236047	NM_006984.5(CLDN10):c.142A>C (p.Asn48His)	Likely pathogenic

SpliceAI

917 predictions. Top by Δscore:

Variant	Effect	Δscore
13:95552946:G:GT	donor_gain	0.9900
13:95553110:GGCCT:G	donor_gain	0.9900
13:95560252:C:G	donor_gain	0.9900
13:95560381:GGGCT:G	acceptor_gain	0.9900
13:95560461:AAA:A	donor_gain	0.9900
13:95560464:G:GG	donor_gain	0.9900
13:95577292:G:GA	donor_gain	0.9900
13:95552942:C:T	donor_gain	0.9800
13:95553028:C:G	donor_gain	0.9800
13:95560290:TCAGG:T	donor_loss	0.9800
13:95560291:CAG:C	donor_loss	0.9800
13:95560292:AG:A	donor_loss	0.9800
13:95560293:GGTAA:G	donor_loss	0.9800
13:95560294:GT:G	donor_loss	0.9800
13:95560295:T:TC	donor_loss	0.9800
13:95560380:AG:A	acceptor_gain	0.9800
13:95560381:GG:G	acceptor_gain	0.9800
13:95560462:AA:A	donor_gain	0.9800
13:95552803:GC:G	donor_gain	0.9700
13:95552844:A:T	donor_gain	0.9700
13:95552903:G:GT	donor_gain	0.9700
13:95552906:GGC:G	donor_gain	0.9700
13:95552907:GCG:G	donor_gain	0.9700
13:95552928:G:GT	donor_gain	0.9700
13:95552970:G:GT	donor_gain	0.9700
13:95553127:G:T	donor_gain	0.9700
13:95560376:TGTTA:T	acceptor_loss	0.9700
13:95560377:GTTA:G	acceptor_loss	0.9700
13:95560378:TTA:T	acceptor_loss	0.9700
13:95560379:TAG:T	acceptor_loss	0.9700

AlphaMissense

1472 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:95552803:G:A	G17D	0.999
13:95552843:G:C	W30C	0.999
13:95552843:G:T	W30C	0.999
13:95552901:T:A	W50R	0.999
13:95552901:T:C	W50R	0.999
13:95552903:G:C	W50C	0.999
13:95552903:G:T	W50C	0.999
13:95552912:C:G	C53W	0.999
13:95552940:T:A	C63S	0.999
13:95552941:G:C	C63S	0.999
13:95560435:T:C	F146L	0.999
13:95560437:C:A	F146L	0.999
13:95560437:C:G	F146L	0.999
13:95577262:T:A	W166R	0.999
13:95577262:T:C	W166R	0.999
13:95552802:G:C	G17R	0.998
13:95552805:T:A	W18R	0.998
13:95552805:T:C	W18R	0.998
13:95552841:T:A	W30R	0.998
13:95552841:T:C	W30R	0.998
13:95552910:T:A	C53S	0.998
13:95552910:T:C	C53R	0.998
13:95552911:G:A	C53Y	0.998
13:95552911:G:C	C53S	0.998
13:95552919:G:C	D56H	0.998
13:95552940:T:C	C63R	0.998
13:95552941:G:A	C63Y	0.998
13:95552942:C:G	C63W	0.998
13:95560151:A:C	R80S	0.998
13:95560151:A:T	R80S	0.998

dbSNP variants (sampled 300 via entrez): RS1000023360 (13:95438014 T>A,C), RS1000054456 (13:95437829 G>A), RS1000079114 (13:95562552 G>T), RS1000111405 (13:95453834 G>A,T), RS1000112305 (13:95517354 G>A), RS1000157844 (13:95436468 A>G), RS1000166169 (13:95443266 C>T), RS1000192604 (13:95444650 G>C), RS1000194890 (13:95535657 A>G), RS1000221249 (13:95453173 A>C), RS1000235740 (13:95562191 C>G,T), RS1000279224 (13:95432248 C>T), RS1000279370 (13:95565424 A>G), RS1000282077 (13:95576165 G>A), RS1000339185 (13:95448364 C>G)

Disease associations

OMIM: gene MIM:617579 | disease phenotypes: MIM:602553, MIM:617671, MIM:602014

GenCC curated gene-disease

Disease	Classification	Inheritance
HELIX syndrome	Strong	Autosomal recessive

Mondo (3): distal monosomy 13q (MONDO:0011248), HELIX syndrome (MONDO:0060564), familial primary hypomagnesemia (MONDO:0018100)

Orphanet (3): Distal deletion 13q syndrome (Orphanet:1590), Hypohidrosis-electrolyte imbalance-lacrimal gland dysfunction-ichthyosis-xerostomia syndrome (Orphanet:528105), OBSOLETE: Genetic primary hypomagnesemia (Orphanet:34526)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000103	Polyuria
HP:0000217	Xerostomia
HP:0000522	Alacrima
HP:0000787	Nephrolithiasis
HP:0000843	Hyperparathyroidism
HP:0000958	Dry skin
HP:0000966	Hypohidrosis
HP:0000970	Anhidrosis
HP:0001959	Polydipsia
HP:0002046	Heat intolerance
HP:0002900	Hypokalemia
HP:0002918	Hypermagnesemia
HP:0003127	Hypocalciuria
HP:0003577	Congenital onset

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004678_5	Psychosis proneness (hypomanic personality scale)	1.000000e-06
GCST008059_218	Estimated glomerular filtration rate	1.000000e-07
GCST009269_15	Dental caries (decayed and filled deciduous teeth)	4.000000e-06
GCST009391_1138	Metabolite levels	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008337	psychosis predisposition measurement
EFO:0010458	alpha-hydroxybutyric acid measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566526	Anal Atresia, Hypospadias, and Penoscrotal Inversion (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	10
trichostatin A	increases expression	2
Nickel	decreases expression	2
Tobacco Smoke Pollution	increases expression	2
methylmercuric chloride	decreases expression	1
apocarotenal	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
quercitrin	affects expression	1
arsenite	increases methylation	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	increases expression	1
Azacitidine	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cisplatin	affects expression	1
Folic Acid	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Phthalic Acids	increases methylation	1
Quercetin	decreases expression	1
Tetracycline	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
beta Carotene	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00282620	PHASE4	UNKNOWN	Magnesium to Reduce Implantable Cardioverter Defibrillator (ICD) Shocks and Improve Patient’s Quality of Life.
NCT00603499	PHASE4	COMPLETED	Magnesium and Metabolic Syndrome
NCT00994006	PHASE4	COMPLETED	The Absorption of Magnesium Oxide Compared to Citrate in Healthy Subjects
NCT03088852	PHASE4	RECRUITING	Magnesium Deficiency In Patients Hospitalized in Internal Medicine Wards
NCT03812380	PHASE3	TERMINATED	Averting Complications of Proton Pump Inhibitor Therapy by Effervescent Calcium Magnesium Citrate
NCT05998863	PHASE3	RECRUITING	EffCaMgCit to Prevent Mineral Metabolism and Renal Complications of Chronic PPI Therapy
NCT02216877	PHASE1/PHASE2	COMPLETED	Magnesium Supplementation for Hypomagnesemia in Chronic Kidney Disease
NCT04382157	PHASE1/PHASE2	UNKNOWN	Magnesium Replacement and Hyperglycemia After Kidney Transplantation
NCT01700998	Not specified	COMPLETED	Magnesium Replacement Therapy to Prevent Acute Renal Failure in Critically Ill Patients
NCT02690012	Not specified	COMPLETED	Feasibility of Using an Integrated Consent Model to Compare Two Standard of Care Regimens for the Management of Hypomagnesemia From Anti-Cancer Therapies
NCT03976440	Not specified	UNKNOWN	Simplified Regional Citrate Anticoagulation Protocols for CVVH, CVVHDF and SLED: a Pilot Study
NCT04351451	Not specified	COMPLETED	Hypomagnesemia and Hypocalcemia Association Following Thyroidectomy
NCT04426994	Not specified	COMPLETED	Hypomagnesemia Associated With Proton-Pump Inhibitor Use
NCT06353750	Not specified	UNKNOWN	Intracellular Magnesium and Heart Failure
NCT06855550	Not specified	COMPLETED	Postoperative Incidence of Atrial Fibrillation Following Cardiac Surgery
NCT07056283	Not specified	RECRUITING	The Study of Urinary Biomarkers in Patients With Hypomagnesemia
NCT07089004	Not specified	COMPLETED	Hypomagnesemia and Its Clinical Outcome
NCT07380542	Not specified	COMPLETED	Dynamic Magnesium Replacement Strategies and 28-Day Mortality in Non-Cardiac Critically Ill Patients With Hypomagnesemia: A Target Trial Emulation
NCT07576621	Not specified	COMPLETED	Association Between Hypomagnesemia and Coagulopathy in Sepsis