SLC14A1

Summary

SLC14A1 (solute carrier family 14 member 1 (Kidd blood group), HGNC:10918) is a protein-coding gene on chromosome 18q12.3, encoding Urea transporter 1 (Q13336). Mediates the transport of urea driven by a concentration gradient across the cell membrane of erythrocytes.

The protein encoded by this gene is a membrane transporter that mediates urea transport in erythrocytes. This gene forms the basis for the Kidd blood group system.

Source: NCBI Gene 6563 — RefSeq curated summary.

At a glance

• Gene–disease (curated): blood group, kidd system (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 73 total — 3 pathogenic, 2 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_015865

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10918
Approved symbol	SLC14A1
Name	solute carrier family 14 member 1 (Kidd blood group)
Location	18q12.3
Locus type	gene with protein product
Status	Approved
Aliases	HsT1341, RACH1, RACH2
Ensembl gene	ENSG00000141469
Ensembl biotype	protein_coding
OMIM	613868
Entrez	6563

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 22 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000321925, ENST00000402943, ENST00000415427, ENST00000436407, ENST00000502059, ENST00000535474, ENST00000586056, ENST00000586142, ENST00000586854, ENST00000586951, ENST00000587601, ENST00000588179, ENST00000589322, ENST00000589700, ENST00000590246, ENST00000590377, ENST00000591541, ENST00000591642, ENST00000619403, ENST00000644925, ENST00000899336, ENST00000899337, ENST00000899338, ENST00000899339, ENST00000899340, ENST00000899341, ENST00000899342, ENST00000964132

RefSeq mRNA: 6 — MANE Select: NM_015865 NM_001128588, NM_001146036, NM_001146037, NM_001308278, NM_001308279, NM_015865

CCDS: CCDS11925, CCDS45860, CCDS77181, CCDS82252

Canonical transcript exons

ENST00000321925 — 10 exons

Exon	Start	End
ENSE00001263021	45724950	45725013
ENSE00001383862	45749778	45752520
ENSE00003489500	45748376	45748425
ENSE00003546283	45730300	45730471
ENSE00003599719	45734274	45734402
ENSE00003607837	45731015	45731204
ENSE00003652400	45739528	45739662
ENSE00003673767	45739163	45739310
ENSE00003787100	45736456	45736648
ENSE00003850265	45724181	45724273

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 98.05.

FANTOM5 (CAGE): breadth broad, TPM avg 15.1858 / max 690.3361, expressed in 719 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170125	12.0532	551
170124	1.3990	296
170126	0.7466	47
170122	0.7306	118
170127	0.1310	56
170128	0.1098	49
170123	0.0156	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	98.05	gold quality
mucosa of urinary bladder	UBERON:0001259	94.32	gold quality
trabecular bone tissue	UBERON:0002483	91.91	gold quality
right coronary artery	UBERON:0001625	91.75	gold quality
urinary bladder	UBERON:0001255	90.55	gold quality
medial globus pallidus	UBERON:0002477	89.44	gold quality
ascending aorta	UBERON:0001496	89.24	gold quality
thoracic aorta	UBERON:0001515	88.98	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.68	gold quality
globus pallidus	UBERON:0001875	88.57	gold quality
cranial nerve II	UBERON:0000941	88.46	gold quality
substantia nigra	UBERON:0002038	88.05	gold quality
prostate gland	UBERON:0002367	87.91	gold quality
descending thoracic aorta	UBERON:0002345	87.90	gold quality
lateral globus pallidus	UBERON:0002476	87.81	gold quality
caudate nucleus	UBERON:0001873	87.07	gold quality
buccal mucosa cell	CL:0002336	87.00	silver quality
apex of heart	UBERON:0002098	86.97	gold quality
putamen	UBERON:0001874	86.87	gold quality
CA1 field of hippocampus	UBERON:0003881	86.62	silver quality
midbrain	UBERON:0001891	86.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.85	gold quality
amygdala	UBERON:0001876	85.72	gold quality
hypothalamus	UBERON:0001898	85.16	gold quality
spinal cord	UBERON:0002240	84.90	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.27	gold quality
Ammon’s horn	UBERON:0001954	84.15	gold quality
inferior olivary complex	UBERON:0002127	83.78	gold quality
metanephros cortex	UBERON:0010533	83.47	gold quality
bone marrow	UBERON:0002371	83.36	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1751.54
E-MTAB-10283	yes	193.82
E-HCAD-25	yes	27.32
E-MTAB-9221	yes	12.71
E-GEOD-84465	yes	10.75
E-GEOD-124858	no	222.69
E-MTAB-9067	no	3.57
E-HCAD-10	no	2.91
E-MTAB-9467	no	0.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFAT5

miRNA regulators (miRDB)

125 targeting SLC14A1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 36)

• gene encodes the Kidd blood group antigens (PMID:12093813)
• Kidd antigen/UT-B urea transporter is physiologically expressed in the human colon epithelium, where it could participate in the transport of urea across the colon mucosa. (PMID:14985236)
• high frequency of JK null allele in Taiwanese indigenous groups (PMID:18713105)
• Three blood group antigens genes, namely CD55, CD151, and SLC14A1, have been subjected to balancing selection, a process, rare outside MHC genes, which maintains variability at a locus. (PMID:18997004)
• Results illustrate differential protein abundance of functional UT-B protein in different sections of the human colon, strongly correlating to regions that contain the largest populations of intestinal bacteria. (PMID:19926813)
• A new allele JK*01W has 3 changes (130G>A, 588A>G, Intron 9-46a>g)in addition to 838G. It is associated with weak expression of the Jk-a antigen on erythrocytes. (PMID:21309779)
• rs17674580, or other sequence variants of SLC14A1, indirectly modifies urinary bladder cancer risk by affecting urine production. (PMID:21750109)
• Genetic variation in SLC14A1 could provide new etiological insights into bladder carcinogenesis. (PMID:21824976)
• Loss of SLC14A1 is associated with lung adenocarcinoma. (PMID:22223368)
• the rate of urea conduction in UT-B is increased by hypoosmotic stress, and the site of osmoregulation coincides with the location of the energy barrier (PMID:22733730)
• Four novel JK-null alleles were noted to be associated with the Jk(a-b-) phenotype. (PMID:22738189)
• Thienoquinoline PU-14 is a selective UT inhibitor and has urea-selective diuretic activity. (PMID:23486518)
• Inhibitor and mutagenesis studies and results of molecular dynamics simulations suggest that NH and HO pass through the three monomeric urea channels in UT-B. (PMID:23552862)
• Data indicate that urea transporter UT-A1 successfully trafficking to the apical membrane of the epithelial cells is crucial for the regulation of urea transport. (PMID:23698785)
• SLC14A1 could be a unique urea transporter in the bladder that has the ability to influence urine concentration and that this mechanism might explain the increased bladder cancer susceptibility associated with rs10775480. (PMID:23754249)
• UT-B should be considered as a new member of the water channel family. (PMID:24376529)
• High-throughput Kell, Kidd, and Duffy matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry-based blood group genotyping of 4000 donors shows close to full concordance with serotyping and detects new alleles. (PMID:24845979)
• Novel polymorphisms in exon 9 of the JSLC14A1 gene in Japanese individuals associated with the Jk(a-b-) phenotype. (PMID:24877238)
• these data confirm the presence of UT-B protein within the human bladder. (PMID:25209859)
• Results suggested that polymorphism in TERTC/T and SLC14A1C/T confirmed high risk for BC in North Indian population. (PMID:25218484)
• Studies indicate that expression of urea transporter UT-B confers high urea permeability to erythrocytes. (PMID:25298342)
• Studies indicate that acid substitution in the urea transporter Slc14A1 UT-B protein determines the erythrocyte Kidd blood group antigen. (PMID:25298346)
• Reduction or loss of UT-B expression may be related to the incidence, progression and invasiveness of bladder urothelial carcinoma. (PMID:25445116)
• The Jk(a-b-) phenotype in the Chinese population shows several different molecular mechanisms. A novel missense mutation nt737T>G of JK gene was found as associated with Jk(a-b-) phenotype. (PMID:25807964)
• In addition to the well known Polynesian Jknull allele, three Jknull alleles were detected including one novel Jknull allele: JKA (130A, 220G). (PMID:26969102)
• The urea transporter subtypes, UT-A1 and UT-B1, were expressed in the skin basal cell layer and exocrine sweat glands. The abundance of UT-A1 and UT-B1 in uremic sweat glands was significantly increased in UP, while the expression of AQP5 was decreased. (PMID:29279852)
• Study found that UT-B expression is decreased in human melanoma tissue. Its overexpression plays a role in tumor growth regulation of melanoma cell lines and animal transplantation models, and this, combined with findings from UT-B inhibition in bladder cancer, suggests that UT-B may have tumor suppressor functions. (PMID:30290033)
• A novel JK null allele in a Brazilian patient with sickle cell disease (SCD). (PMID:30964549)
• Decreased Expression of the Human Urea Transporter SLC14A1 in Bone is Induced by Cytokines and Stimulates Adipogenesis of Mesenchymal Progenitor Cells. (PMID:31958845)
• SLC14A1 prevents oncometabolite accumulation and recruits HDAC1 to transrepress oncometabolite genes in urothelial carcinoma. (PMID:33052246)
• Diversity of variant alleles encoding Kidd, Duffy, and Kell antigens in individuals with sickle cell disease using whole genome sequencing data from the NHLBI TOPMed Program. (PMID:33231305)
• A potential link between AQP3 and SLC14A1 gene expression level and clinical parameters of maintenance hemodialysis patients. (PMID:36038817)
• Study on the role of SLC14A1 gene in biochemical recurrence of prostate cancer. (PMID:36257969)
• SLC14A1 is a new biomarker in renal cancer. (PMID:37004669)
• Down-regulation of SLC14A1 in prostate cancer activates CDK1/CCNB1 and mTOR pathways and promotes tumor progression. (PMID:38942821)
• SLC14A1 and TGF-beta signaling: a feedback loop driving EMT and colorectal cancer metachronous liver metastasis. (PMID:39061061)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc14a2	ENSDARG00000051914
mus_musculus	Slc14a1	ENSMUSG00000059336
rattus_norvegicus	Slc14a1	ENSRNOG00000016753

Paralogs (1): SLC14A2 (ENSG00000132874)

Protein

Protein identifiers

Urea transporter 1 — Q13336 (reviewed: Q13336)

Alternative names: Solute carrier family 14 member 1, Urea transporter, erythrocyte

All UniProt accessions (11): B4DFJ8, E9NSU1, Q13336, F5GWS2, F6WB45, G0W2N5, K7EJ54, K7EJF6, K7EQM7, K7ESL3, M0QYS8

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the transport of urea driven by a concentration gradient across the cell membrane of erythrocytes. Also mediates the transport of urea across the cell membrane of the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism. Facilitates water transport in erythrocytes.

Subunit / interactions. Homotrimer; each subunit contains a pore through which urea permeates. Identified in a complex with STOM.

Subcellular location. Cell membrane. Basolateral cell membrane.

Tissue specificity. Detected in erythrocytes (at protein level). Expressed in spleen erythroblasts and tumoral kidney.

Activity regulation. Inhibited by phloretin and para-chloromercuribenzene sulfonate.

Polymorphism. SLC14A1 is responsible for the Kidd blood group system (JK) [MIM:111000]. JK is defined by 2 alleles, JK01 and JK02 that give rise to Jk(a) and Jk(b) antigens respectively. The molecular basis of the Jk(a)/Jk(b) antigens is a single variation in position 280; Asp-280 corresponds to Jk(a) and Asn-280 to Jk(b). Some individuals carry silenced JK01 and JK02 alleles, designated JK01N or JK02N. They results in a Jk(null) phenotype associated with reduced urea permeability of red blood cells. Jk(null) is not associated with any obvious clinical syndrome except for a urine concentration defect.

Similarity. Belongs to the urea transporter family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13336-1	1	yes
Q13336-2	2

RefSeq proteins (6): NP_001122060, NP_001139508, NP_001139509, NP_001295207, NP_001295208, NP_056949* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004937	Urea_transporter	Family
IPR029020	Ammonium/urea_transptr	Homologous_superfamily

Pfam: PF03253

Catalyzed reactions (Rhea), 1 shown:

• urea(in) = urea(out) (RHEA:32799)

UniProt features (53 total): helix 23, transmembrane region 9, sequence variant 8, turn 4, sequence conflict 3, strand 2, chain 1, site 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6QD5	X-RAY DIFFRACTION	2.4
8XDF	ELECTRON MICROSCOPY	2.4
8BLP	ELECTRON MICROSCOPY	2.6
9J22	ELECTRON MICROSCOPY	2.75
9ZD0	ELECTRON MICROSCOPY	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13336-F1	92.94	0.89

Functional residue map

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

Catalytic / active sites (1): 339 (important for channel permeability)

Glycosylation sites (1): 211

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-549127	SLC-mediated transport of organic cations
R-HSA-425366

MSigDB gene sets: 0 (showing top):

GO Biological Process (5): urea transport (GO:0015840), establishment of localization in cell (GO:0051649), transmembrane transport (GO:0055085), urea transmembrane transport (GO:0071918), water transport (GO:0006833)

GO Molecular Function (4): water transmembrane transporter activity (GO:0005372), urea transmembrane transporter activity (GO:0015204), urea channel activity (GO:0015265), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transporter activity	2
one-carbon compound transport	1
nitrogen compound transport	1
establishment of localization	1
cellular localization	1
transport	1
cellular process	1
urea transport	1
transmembrane transport	1
fluid transport	1
water transport	1
urea transmembrane transport	1
urea transmembrane transporter activity	1
channel activity	1
binding	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC14A1	CFB	P00751	648
SLC14A1	GATA1	P15976	592
SLC14A1	KEL	P23276	542
SLC14A1	UGT1A10	Q9HAW8	513
SLC14A1	UGT1A8	Q9HAW9	513
SLC14A1	UGT1A6	P19224	508
SLC14A1	ZNF134	P52741	507
SLC14A1	RHCE	P18577	506
SLC14A1	UGT1A1	P22309	506
SLC14A1	UGT1A7	Q9HAW7	506
SLC14A1	UGT1A4	P22310	500
SLC14A1	ZNF160	Q9HCG1	479
SLC14A1	AQP3	Q92482	476
SLC14A1	ERMAP	Q96PL5	452
SLC14A1	SLC4A1	P02730	449

IntAct

9 interactions, top by confidence:

A	B	Type	Score
SLC4A1	FLOT1	psi-mi:“MI:0914”(association)	0.530
SCRIB	SLC14A1	psi-mi:“MI:0407”(direct interaction)	0.440
CFTR	SLC14A1	psi-mi:“MI:0915”(physical association)	0.370
ATP2B4	FLOT1	psi-mi:“MI:0914”(association)	0.350
SLC14A1	UBB	psi-mi:“MI:0914”(association)	0.350
SLC14A1	ATP6AP2	psi-mi:“MI:0914”(association)	0.350
SLC14A1	PLXNB2	psi-mi:“MI:0914”(association)	0.350

BioGRID (57): SLC14A1 (Two-hybrid), SLC14A1 (Two-hybrid), SLC14A1 (Two-hybrid), SLC14A1 (Two-hybrid), THSD7B (Two-hybrid), TMIE (Two-hybrid), C2orf82 (Two-hybrid), RTP2 (Two-hybrid), GIMAP1 (Two-hybrid), FIS1 (Two-hybrid), LOC100507537 (Two-hybrid), UBB (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IQZ2, A1KSH5, A6V3A0, A9M2A8, A9RA88, B7UZU0, C4LD54, C5MK33, D3INW7, E9PXX9, O00337, O43868, O62667, O88575, O88627, O97681, P15920, P20715, P97689, Q02PG0, Q13336, Q15849, Q28614, Q28GF5, Q4V7N7, Q5F410, Q5F6X7, Q5QF96, Q5R687, Q5U4Q2, Q62668, Q62674, Q62773, Q6C741, Q6PQZ3, Q6UPR8, Q72CX3, Q7EYH7, Q7Z2K6, Q8R4T9

Diamond homologs: C5MK33, D3INW7, P97689, Q13336, Q15849, Q28614, Q5QF96, Q62668, Q72CX3, Q8R4T9, Q8VHL0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	43
Likely benign	5
Benign	10

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
17719	NM_015865.7(SLC14A1):c.663+1G>T	Pathogenic
17720	NM_015865.7(SLC14A1):c.871T>C (p.Ser291Pro)	Pathogenic
17721	NM_015865.7(SLC14A1):c.-21-131_341+571del	Pathogenic
17718	NM_015865.7(SLC14A1):c.342-1G>A	Likely pathogenic
2636442	NM_015865.7(SLC14A1):c.264_265dup (p.Asn89fs)	Likely pathogenic

SpliceAI

1654 predictions. Top by Δscore:

Variant	Effect	Δscore
18:45724269:GTGGT:G	donor_gain	1.0000
18:45724270:TGGT:T	donor_gain	1.0000
18:45724271:GGTG:G	donor_gain	1.0000
18:45724272:GT:G	donor_gain	1.0000
18:45724274:G:GG	donor_gain	1.0000
18:45727251:AT:A	acceptor_gain	1.0000
18:45727252:T:G	acceptor_gain	1.0000
18:45727256:T:G	acceptor_gain	1.0000
18:45724273:TG:T	donor_loss	0.9900
18:45724274:G:GA	donor_loss	0.9900
18:45727251:A:AG	acceptor_gain	0.9900
18:45727252:T:TA	acceptor_gain	0.9900
18:45727255:A:AG	acceptor_gain	0.9900
18:45727255:ATT:A	acceptor_gain	0.9900
18:45727257:T:A	acceptor_gain	0.9900
18:45729984:A:AG	acceptor_gain	0.9900
18:45729985:G:GG	acceptor_gain	0.9900
18:45731013:A:AG	acceptor_gain	0.9900
18:45731014:G:GA	acceptor_gain	0.9900
18:45731014:GAC:G	acceptor_gain	0.9900
18:45739307:GCGG:G	donor_gain	0.9900
18:45739660:GTG:G	donor_gain	0.9900
18:45749772:CCCCA:C	acceptor_loss	0.9900
18:45749773:CCCA:C	acceptor_loss	0.9900
18:45749775:CA:C	acceptor_loss	0.9900
18:45749777:G:GA	acceptor_loss	0.9900
18:45724868:G:GT	donor_gain	0.9800
18:45727247:T:TA	acceptor_gain	0.9800
18:45729282:G:GA	donor_gain	0.9800
18:45731009:TTCCA:T	acceptor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000012987 (18:45746082 C>T), RS1000075611 (18:45739874 G>A), RS1000107337 (18:45734368 C>G,T), RS1000281392 (18:45728607 A>C), RS1000412027 (18:45733556 A>C), RS1000616971 (18:45744342 A>G), RS1000638627 (18:45751813 T>C), RS1000691223 (18:45738493 C>T), RS1000721542 (18:45751659 T>A), RS1000773872 (18:45751256 C>G,T), RS1000859477 (18:45726213 G>A), RS1000867960 (18:45738795 G>A), RS1001001363 (18:45726907 C>A), RS1001332142 (18:45740963 G>A), RS1001371537 (18:45732516 G>C,T)

Disease associations

OMIM: gene MIM:613868 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
blood group, kidd system	Limited	Autosomal dominant
nephrogenic diabetes insipidus	No Known Disease Relationship	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nephrogenic diabetes insipidus	No Known Disease Relationship	AR

Mondo (2): nephrogenic diabetes insipidus (MONDO:0016383), (MONDO:0020612)

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001153_1	Bladder cancer	8.000000e-11
GCST001193_1	Bladder cancer	9.000000e-09
GCST005024_109	Pursuit maintenance gain	3.000000e-06
GCST005992_25	Mean corpuscular hemoglobin concentration	3.000000e-48
GCST010538_9	Sum of carotid plaque area	5.000000e-06
GCST010539_8	Sum of stenosis	3.000000e-07
GCST90002385_336	High light scatter reticulocyte count	5.000000e-18
GCST90002386_85	High light scatter reticulocyte percentage of red cells	3.000000e-16
GCST90002387_211	Immature fraction of reticulocytes	6.000000e-18

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0006501	carotid plaque build
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018500	Diabetes Insipidus, Nephrogenic	C12.050.351.968.419.135.500; C12.200.777.419.135.500; C12.950.419.135.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2390814 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2298720	SLC14A1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC14 family of facilitative urea transporters

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 1a [PMID: 23597791]	Inhibition	7.96	pIC50
compound E3	Inhibition	7.6	pIC50
compound 8ay [PMID: 29589443]	Inhibition	5.7	pIC50

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.96	IC50	11	nM	CHEMBL1394231
5.76	IC50	1720	nM	CHEMBL4454312

PubChem BioAssay actives

2 with measured affinity, of 3 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
10-(4-ethylphenyl)sulfonyl-N-(thiophen-2-ylmethyl)-5-thia-1,8,11,12-tetrazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaen-7-amine	752404: Inhibition of UT-B in human erythrocytes assessed as increase of hypotonic lysis	ic50	0.0110	uM
1-(3-amino-6-methylthieno[2,3-b]quinolin-2-yl)ethanone	1551208: Inhibition of urea transporter B in human erythrocytes incubated for 6 mins by spectrophotometric analysis based erythrocyte lysis assay	ic50	1.7200	uM

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Estradiol	decreases expression, affects cotreatment	2
Nickel	decreases expression	2
Progesterone	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
methylselenic acid	increases expression	1
cinnamaldehyde	increases expression	1
mancozeb	decreases expression	1
sodium arsenite	decreases expression	1
zinc chromate	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
2-palmitoylglycerol	increases expression	1
clothianidin	decreases expression	1
incobotulinumtoxinA	increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	affects response to substance	1
Zoledronic Acid	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Carmustine	affects response to substance	1
Hydroxyurea	increases uptake	1
Malathion	decreases expression	1
Melphalan	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2394862	Binding	Inhibition of UT-B in human erythrocytes assessed as increase of hypotonic lysis	1,1-Difluoroethyl-substituted triazolothienopyrimidines as inhibitors of a human urea transport protein (UT-B): new analogs and binding model. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05190744	PHASE2	COMPLETED	Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration
NCT00478335	Not specified	COMPLETED	Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus
NCT04939753	Not specified	COMPLETED	Nephrogenic Diabetes Insipidus During Prolonged Sevoflurane Sedation in the ICU: a Retrospective Analysis
NCT05307042	Not specified	UNKNOWN	Decline in Renal Concentration Ability in Lithium Treated Patients
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06604975	Not specified	NOT_YET_RECRUITING	Arginin-stimulated Copeptin in Polyuria-polydipsia Syndrome in Children