TAX1BP3

Summary

TAX1BP3 (Tax1 binding protein 3, HGNC:30684) is a protein-coding gene on chromosome 17p13.2, encoding Tax1-binding protein 3 (O14907). May regulate a number of protein-protein interactions by competing for PDZ domain binding sites.

This gene encodes a small, highly conserved protein with a single PDZ domain. PDZ (PSD-95/Discs large/ZO-1 homologous) domains promote protein-protein interactions that affect cell signaling, adhesion, protein scaffolding, and receptor and ion transporter functions. The encoded protein interacts with a large number of target proteins that play roles in signaling pathways; for example, it interacts with Rho A and glutaminase L and also acts as a negative regulator of the Wnt/beta-catenin signaling pathway. This protein was first identified as binding to the T-cell leukaemia virus (HTLV1) Tax oncoprotein. Overexpression of this gene has been implicated in altered cancer cell adhesion, migration and metastasis. The encoded protein also modulates the localization and density of inwardly rectifying potassium channel 2.3 (Kir2.3). To date, this protein has been shown to play a role in cell proliferation, development, stress response, and polarization. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 30851 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total — 2 likely-pathogenic
• MANE Select transcript: NM_014604

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30684
Approved symbol	TAX1BP3
Name	Tax1 binding protein 3
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	TIP-1
Ensembl gene	ENSG00000213977
Ensembl biotype	protein_coding
OMIM	616484
Entrez	30851

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000225525, ENST00000611779, ENST00000874102, ENST00000874103, ENST00000920138, ENST00000920139

RefSeq mRNA: 2 — MANE Select: NM_014604 NM_001204698, NM_014604

CCDS: CCDS11032, CCDS73940

Canonical transcript exons

ENST00000225525 — 4 exons

Exon	Start	End
ENSE00001196698	3668488	3668578
ENSE00001301026	3662895	3663885
ENSE00003462929	3664195	3664272
ENSE00003572585	3664679	3664798

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 113.5287 / max 1404.7012, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163859	101.1440	1816
163860	12.3412	1789
163861	0.0436	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	98.75	gold quality
apex of heart	UBERON:0002098	98.73	gold quality
esophagus mucosa	UBERON:0002469	98.66	gold quality
endocervix	UBERON:0000458	98.56	gold quality
mucosa of transverse colon	UBERON:0004991	98.44	gold quality
ectocervix	UBERON:0012249	98.43	gold quality
vagina	UBERON:0000996	98.23	gold quality
metanephros cortex	UBERON:0010533	98.21	gold quality
lower esophagus mucosa	UBERON:0035834	98.13	gold quality
heart left ventricle	UBERON:0002084	98.11	gold quality
right atrium auricular region	UBERON:0006631	98.11	gold quality
left coronary artery	UBERON:0001626	97.86	gold quality
right adrenal gland cortex	UBERON:0035827	97.83	gold quality
right adrenal gland	UBERON:0001233	97.82	gold quality
ascending aorta	UBERON:0001496	97.79	gold quality
thoracic aorta	UBERON:0001515	97.79	gold quality
body of stomach	UBERON:0001161	97.77	gold quality
heart	UBERON:0000948	97.76	gold quality
left adrenal gland cortex	UBERON:0035825	97.70	gold quality
right coronary artery	UBERON:0001625	97.69	gold quality
stromal cell of endometrium	CL:0002255	97.68	gold quality
left adrenal gland	UBERON:0001234	97.63	gold quality
gall bladder	UBERON:0002110	97.54	gold quality
esophagus	UBERON:0001043	97.53	gold quality
skin of abdomen	UBERON:0001416	97.51	gold quality
body of uterus	UBERON:0009853	97.51	gold quality
duodenum	UBERON:0002114	97.46	gold quality
fundus of stomach	UBERON:0001160	97.45	gold quality
left uterine tube	UBERON:0001303	97.38	gold quality
transverse colon	UBERON:0001157	97.35	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	211.01
E-CURD-114	yes	75.05
E-GEOD-125970	yes	22.91
E-HCAD-11	yes	21.74
E-ANND-3	yes	17.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting TAX1BP3, 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-6825-5P	99.96	69.81	3431
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-7976	95.75	65.67	1186
HSA-MIR-6820-5P	94.04	61.13	161

Literature-anchored findings (GeneRIF, showing 13)

• TIP-1 may represent a novel regulatory element in the Wnt/beta-catenin signaling pathway (PMID:12874278)
• HPV16 E6 protein may increase cell motility by augmenting GTP RhoA mediated activation of RhoA kinases and that this is dependent on the expression of the Tip-1 protein (PMID:15492812)
• TIP-1 is ubiquitously expressed, raising the possibility that TIP-1 may play a similar role in regulating the expression of other membrane proteins containing a type I PDZ ligand. (PMID:16855024)
• the overexpression, efficient refolding, single-step purification, and biophysical characterization of recombinant human TIP-1 with three different C-terminal target protein recognition sequence motifs by CD, fluorescence, and NMR methods (PMID:18690705)
• TIP-1 may act as an important regulator for the endocytic pathway of Kir2.3. (PMID:19635485)
• HPV16 E6, Tip-1 and ARHGEF16 may cooperate to activate Cdc42 and support a potential link between the expression of HPV16 E6 and Cdc42 activation. (PMID:21139582)
• This is the first study reporting BAI2 as an interaction partner of GIP. (PMID:21787750)
• this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers. (PMID:22564736)
• The study reports the identification of 18 new glutaminase-interacting protein - binding peptides with novel internal motifs that map to a number of candidate human glutaminase-interacting protein partner proteins. (PMID:22876914)
• The study provided the first evidence showing that TIP-1 modulates p53 protein stability and is involved in the radioresistance of malignant gliomas. (PMID:23028987)
• this study reports the identification of two new hGIP-interacting partners, DTX1 and STAU1. (PMID:23395680)
• ARHGEF7, a guanine nucleotide exchange factor for Rho GTPases, as one novel TIP-1-interacting protein in human glioblastoma cells (PMID:23563176)
• Mutations in TAX1BP3 cause dilated cardiomyopathy with septo-optic dysplasia (PMID:25645515)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tax1bp3	ENSDARG00000059177
mus_musculus	Tax1bp3	ENSMUSG00000040158
rattus_norvegicus	Tax1bp3	ENSRNOG00000019357
drosophila_melanogaster	CG3402	FBGN0035148
caenorhabditis_elegans		WBGENE00016678

Protein

Protein identifiers

Tax1-binding protein 3 — O14907 (reviewed: O14907)

Alternative names: Glutaminase-interacting protein 3, Tax interaction protein 1, Tax-interacting protein 1

All UniProt accessions (2): A0A087X282, O14907

UniProt curated annotations — full annotation on UniProt →

Function. May regulate a number of protein-protein interactions by competing for PDZ domain binding sites. Binds CTNNB1 and may thereby act as an inhibitor of the Wnt signaling pathway. Competes with LIN7A for KCNJ4 binding, and thereby promotes KCNJ4 internalization. May play a role in the Rho signaling pathway. May play a role in activation of CDC42 by the viral protein HPV16 E6.

Subunit / interactions. Interacts (via its PDZ domain) with GLS2. Interacts (via its PDZ domain) with RTKN (via the C-terminal region); this interaction facilitates Rho-mediated activation of the FOS serum response element (SRE). Interacts (via its PDZ domain) with CTNNB1; this interaction inhibits the transcriptional activity of CTNNB1. Interacts with HTLV-1 TAX protein. Interacts (via PDZ domain) with ARHGEF16. Interacts (via PDZ domain) with KCNJ4 (via C-terminus). Competes with LIN7A for KCNJ4 binding. Interacts with ADGRB2.

Subcellular location. Cytoplasm. Nucleus. Cell membrane.

Tissue specificity. Ubiquitous. Detected in brain, heart, kidney, lung, small intestine and skeletal muscle. Detected in various cell lines including HeLa. Weakly expressed in peripheral blood leukocytes.

RefSeq proteins (2): NP_001191627, NP_055419* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR017268	Tax1-binding_p3	Family
IPR036034	PDZ_sf	Homologous_superfamily
IPR050614	Synaptic_Scaffolding_LAP-MAGUK	Family

Pfam: PF00595

Enzyme classification (BRENDA):

• EC 3.5.1.2 — glutaminase (BRENDA: 56 organisms, 201 substrates, 332 inhibitors, 107 Km, 53 kcat entries)

Substrate kinetics (BRENDA)

30 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-GLUTAMINE	0.0053–460	51
GLN	0.42–21	12
L-ASPARAGINE	0.1–0.29	5
L-GLN	2.6–6.5	4
GLUTAMINE	4.8–109.5	3
2-OXO-SUCCINAMATE	0.003–0.017	2
GLUTARAMATE	1.27–1.48	2
L-ASN	4.8–24	2
L-GLUTAMIC ACID	5.13–500	2
SUCCINAMATE	0.14–0.23	2
2-OXO-GLUTARAMATE	0.195	1
5-METHOXY-2,5-DIOXOPENTANOIC ACID	0.012	1
D-GAMMA-GLN-METHYLESTER	6.7	1
D-GLUTAMINE	83	1
D-THEANINE	0.92	1

UniProt features (27 total): strand 14, helix 3, turn 2, modified residue 2, mutagenesis site 2, initiator methionine 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
3SFJ	X-RAY DIFFRACTION	1.24
4E3B	X-RAY DIFFRACTION	1.5
4NNL	X-RAY DIFFRACTION	1.5
4NNM	X-RAY DIFFRACTION	1.6
2VZ5	X-RAY DIFFRACTION	1.74
3GJ9	X-RAY DIFFRACTION	2.8
2KG2	SOLUTION NMR
2L4S	SOLUTION NMR
2L4T	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14907-F1	91.40	0.77

Functional residue map

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

Post-translational modifications (2): 2, 61

Mutagenesis-validated functional residues (2):

Position	Phenotype
20	abolishes interaction with kcnj4.
90	abolishes interaction with kcnj4.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5666185	RHO GTPases Activate Rhotekin and Rhophilins

MSigDB gene sets: 207 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GGGTGGRR_PAX4_03, YY1_Q6, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, MODULE_120, SESTO_RESPONSE_TO_UV_C3, GOBP_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, BLALOCK_ALZHEIMERS_DISEASE_UP, LIAO_METASTASIS, GOBP_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP

GO Biological Process (6): Rho protein signal transduction (GO:0007266), negative regulation of cell population proliferation (GO:0008285), Wnt signaling pathway (GO:0016055), negative regulation of Wnt signaling pathway (GO:0030178), regulation of Cdc42 protein signal transduction (GO:0032489), negative regulation of protein localization to cell surface (GO:2000009)

GO Molecular Function (2): beta-catenin binding (GO:0008013), protein binding (GO:0005515)

GO Cellular Component (8): fibrillar center (GO:0001650), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), extracellular exosome (GO:0070062), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase Effectors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
small GTPase-mediated signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell surface receptor signaling pathway	1
negative regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
Cdc42 protein signal transduction	1
regulation of Rho protein signal transduction	1
protein localization to cell surface	1
negative regulation of protein localization	1
regulation of protein localization to cell surface	1
protein binding	1
binding	1
nucleolus	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cytoskeleton	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAX1BP3	GIPC1	O14908	932
TAX1BP3	METTL8	Q9H825	876
TAX1BP3	SOCS1	O15524	778
TAX1BP3	KCNJ4	P48050	740
TAX1BP3	CTNNB1	P35222	692
TAX1BP3	ARHGEF16	Q5VV41	678
TAX1BP3	BAZ2A	Q9UIF9	583
TAX1BP3	RHOA	P06749	554
TAX1BP3	CUTA	O60888	547
TAX1BP3	CNTN2	P78432	535
TAX1BP3	CLIP1	P30622	529
TAX1BP3	P2RX5	Q93086	517
TAX1BP3	ARHGEF7	Q14155	509
TAX1BP3	ITFG1	Q8TB96	507
TAX1BP3	GEMIN6	Q8WXD5	507

IntAct

400 interactions, top by confidence:

A	B	Type	Score
CTNNB1	TAX1BP3	psi-mi:“MI:0915”(physical association)	0.760
CTNNB1	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.760
TAX1BP3	ARVCF	psi-mi:“MI:0914”(association)	0.690
TANC2	TAX1BP3	psi-mi:“MI:0914”(association)	0.690
CIT	TAX1BP3	psi-mi:“MI:0914”(association)	0.690
CIT	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.690
TAX1BP3	RTKN	psi-mi:“MI:0407”(direct interaction)	0.690
TAX1BP3	TANC2	psi-mi:“MI:0407”(direct interaction)	0.690
TAX1BP3	TANC1	psi-mi:“MI:0407”(direct interaction)	0.690
APC	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.690
PKP4	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.690
ARVCF	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.690
E6	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.660
E6	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.650
E6	TAX1BP3	psi-mi:“MI:0914”(association)	0.650
CTNND2	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.590
TAX1BP3	TJP2	psi-mi:“MI:0407”(direct interaction)	0.590
RNF183	TAX1BP3	psi-mi:“MI:0915”(physical association)	0.560
TAX1BP3	RNF183	psi-mi:“MI:0915”(physical association)	0.560
INAVA	DCTN6	psi-mi:“MI:0914”(association)	0.530
CDH8	ARVCF	psi-mi:“MI:0914”(association)	0.530
E6	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.520
TAX1BP3	Tax	psi-mi:“MI:0407”(direct interaction)	0.520
TAX1BP3	E6	psi-mi:“MI:0407”(direct interaction)	0.440
E6	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (83): RNF183 (Two-hybrid), TAX1BP3 (Affinity Capture-MS), TAX1BP3 (Affinity Capture-RNA), TAX1BP3 (Synthetic Lethality), TAX1BP3 (Two-hybrid), TAX1BP3 (Affinity Capture-MS), TAX1BP3 (Positive Genetic), TAX1BP3 (Positive Genetic), TAX1BP3 (Protein-peptide), TAX1BP3 (Affinity Capture-MS), TAX1BP3 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), PAK3 (Affinity Capture-MS), PAK2 (Affinity Capture-MS), CDH1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5G4, A2ALK8, A8MUH7, A9CB74, F1M386, F1MSG6, F1PBJ0, O14745, O14907, O14936, O70589, P19878, P26045, P70290, P70441, P70600, Q00013, Q09506, Q14289, Q17QN6, Q28619, Q3SZK8, Q3T0X8, Q4L1J4, Q4R6G4, Q570Y9, Q5F488, Q5RCF7, Q5RDW4, Q5T2W1, Q5TCQ9, Q5ZIJ9, Q5ZJ00, Q60629, Q62915, Q69ZS7, Q6RHR9, Q865P3, Q8CHG7, Q8TB45

Diamond homologs: A0A8C0TYJ0, A0A8P0N4K0, A5PKA5, F1MCA7, G5ECY0, O14907, O14910, O35274, O35867, O55164, O61967, O62674, O62675, O62676, O88951, O88952, P31016, P57105, P70175, P70587, P78352, P97879, Q0P5E6, Q0P5F3, Q12959, Q13424, Q13425, Q13884, Q14160, Q15599, Q22638, Q28626, Q28C55, Q2KIB6, Q32LE7, Q32LM6, Q3T0C9, Q3UHD6, Q4H4B6, Q5EBL8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 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
Long-term potentiation	5	19.3×	5e-04
Phase 0 - rapid depolarisation	5	14.1×	1e-03
Voltage gated Potassium channels	6	11.8×	8e-04
Assembly and cell surface presentation of NMDA receptors	5	10.3×	4e-03
Potassium Channels	9	9.8×	5e-05
Cardiac conduction	11	9.7×	5e-06
G alpha (12/13) signalling events	8	8.9×	4e-04
RHOB GTPase cycle	7	8.8×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of synaptic transmission, glutamatergic	6	23.0×	2e-04
action potential	7	15.4×	2e-04
synaptic transmission, glutamatergic	5	11.0×	1e-02
sodium ion transmembrane transport	7	8.7×	4e-03
transport across blood-brain barrier	7	7.7×	6e-03
cell-cell adhesion	11	6.8×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	0
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1698538	NC_000017.10:g.(?3539761)(3566398_?)del	Likely pathogenic
598746	Single allele	Likely pathogenic

SpliceAI

735 predictions. Top by Δscore:

Variant	Effect	Δscore
17:3663893:C:CT	acceptor_gain	1.0000
17:3663893:C:T	acceptor_gain	1.0000
17:3663894:A:T	acceptor_gain	1.0000
17:3664674:CTCA:C	donor_loss	1.0000
17:3664675:TCA:T	donor_loss	1.0000
17:3664675:TCAC:T	donor_loss	1.0000
17:3664676:CA:C	donor_loss	1.0000
17:3664676:CACCT:C	donor_loss	1.0000
17:3664677:A:AG	donor_loss	1.0000
17:3664677:A:T	donor_loss	1.0000
17:3664678:C:A	donor_loss	1.0000
17:3664678:C:T	donor_loss	1.0000
17:3664794:CTTTG:C	acceptor_gain	1.0000
17:3664795:TTTG:T	acceptor_gain	1.0000
17:3664799:C:CC	acceptor_gain	1.0000
17:3663883:CAC:C	acceptor_gain	0.9900
17:3663886:C:CC	acceptor_gain	0.9900
17:3663887:T:G	acceptor_loss	0.9900
17:3664271:CC:C	acceptor_gain	0.9900
17:3664272:CC:C	acceptor_gain	0.9900
17:3664792:CTCTT:C	acceptor_gain	0.9900
17:3664793:TCTTT:T	acceptor_gain	0.9900
17:3664795:TTTGC:T	acceptor_loss	0.9900
17:3664796:T:C	acceptor_gain	0.9900
17:3664796:T:TC	acceptor_gain	0.9900
17:3664797:TG:T	acceptor_gain	0.9900
17:3664797:TGCTG:T	acceptor_loss	0.9900
17:3664798:GCTGG:G	acceptor_loss	0.9900
17:3664799:C:CA	acceptor_loss	0.9900
17:3664800:T:A	acceptor_loss	0.9900

AlphaMissense

799 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:3664262:A:T	V57D	1.000
17:3663803:A:G	L107P	0.999
17:3663833:A:G	L97P	0.999
17:3663845:G:T	A93D	0.999
17:3664202:A:C	I77S	0.999
17:3664220:A:G	L71P	0.999
17:3664235:G:T	A66D	0.999
17:3664731:C:T	G36E	0.999
17:3664734:C:T	G35D	0.999
17:3664740:A:T	I33N	0.999
17:3664746:A:G	F31S	0.999
17:3664749:C:T	G30D	0.999
17:3664750:C:G	G30R	0.999
17:3663833:A:T	L97H	0.998
17:3663842:C:G	R94P	0.998
17:3663846:C:G	A93P	0.998
17:3664196:T:G	Q79P	0.998
17:3664202:A:G	I77T	0.998
17:3664202:A:T	I77N	0.998
17:3664208:T:A	D75V	0.998
17:3664208:T:C	D75G	0.998
17:3664208:T:G	D75A	0.998
17:3664266:A:C	Y56D	0.998
17:3664731:C:A	G36V	0.998
17:3664734:C:A	G35V	0.998
17:3664749:C:A	G30V	0.998
17:3663800:A:G	L108P	0.997
17:3663855:G:C	H90D	0.997
17:3663880:G:C	N81K	0.997
17:3663880:G:T	N81K	0.997

dbSNP variants (sampled 300 via entrez): RS1000818427 (17:3664500 G>A,T), RS1000985695 (17:3669891 G>A), RS1001820069 (17:3663278 G>A,C), RS1001856384 (17:3662759 G>A,C), RS1002308994 (17:3662525 A>G), RS1002998018 (17:3667316 C>A), RS1003040033 (17:3665978 T>TG), RS1003547635 (17:3666140 G>A,T), RS1004413091 (17:3670417 C>T), RS1004511970 (17:3669629 C>T), RS1004972922 (17:3664516 C>A,G,T), RS1005127053 (17:3669976 G>A), RS1005429563 (17:3668836 C>A,T), RS1005488517 (17:3665257 A>G), RS1005559733 (17:3663555 G>A)

Disease associations

OMIM: gene MIM:616484 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): cystinosis (MONDO:0016239)

Orphanet (1): Cystinosis (Orphanet:213)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003554	Cystinosis	C16.320.565.595.377; C18.452.648.595.377

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases expression	4
trichostatin A	affects cotreatment, increases expression	2
sodium arsenite	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
chloropicrin	decreases expression	2
(+)-JQ1 compound	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance	2
Tetrachlorodibenzodioxin	increases expression	2
Valproic Acid	affects expression, increases methylation	2
FR900359	increases phosphorylation	1
bisphenol A	affects cotreatment, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
coumarin	decreases phosphorylation	1
4-phenylbutyric acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
CP 31398	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases expression	1
Caffeine	decreases phosphorylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01000961	PHASE3	COMPLETED	Phase 3 Study of Cysteamine Bitartrate Delayed-release (RP103) Compared to Cystagon® in Patients With Cystinosis
NCT01197378	PHASE3	COMPLETED	Long-Term Safety Follow-up Study of Cysteamine Bitartrate Delayed-release Capsules (RP103)
NCT01733316	PHASE3	COMPLETED	Open-Label, Safety and Superior Effectiveness Study of Cysteamine Bitartrate Delayed-Release Capsules (RP103) in Cystinosis
NCT01744782	PHASE3	COMPLETED	Safety/Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naive Patients With Cystinosis
NCT04125927	PHASE3	COMPLETED	Cystadrops in Pediatric Cystinosis Patients From Six Months to Less Than Two Years Old (SCOB2)
NCT00001213	PHASE2	COMPLETED	Cysteamine Eye Drops to Treat Corneal Crystals in Cystinosis
NCT04069260	PHASE2	TERMINATED	A Phase 2 Study of ELX-02 in Patients With Nephropathic Cystinosis
NCT00001736	PHASE1	COMPLETED	New Cysteamine Eye Drops Formulation to Treat Corneal Crystals in Cystinosis
NCT00872729	PHASE1/PHASE2	COMPLETED	Pilot Study of Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of RP103 Compared to Cystagon® in Patients With Cystinosis
NCT02124070	PHASE1/PHASE2	WITHDRAWN	Therapeutic Effect of Recombinant Human Growth Hormone (rhGH) on the Myopathy of Cystinosis
NCT03897361	PHASE1/PHASE2	COMPLETED	Stem Cell Gene Therapy for Cystinosis
NCT05508009	PHASE1/PHASE2	RECRUITING	Early Trial of Allogeneic Hematopoietic Stem Cell Transplantation for Patients Who Will Receive a Kidney Transplant From the Same Donor
NCT05994534	PHASE1/PHASE2	RECRUITING	PK and PD Study of NPI-001 and Cysteamine Bitartrate
NCT02533076	EARLY_PHASE1	COMPLETED	The Functional Consequences of the CTNS-deletion for the TRPV1-receptor in Cystinosis Patients
NCT00004312	Not specified	COMPLETED	Establishment of a Database for Long-Term Monitoring of Patients With Nephropathic Cystinosis
NCT00004350	Not specified	COMPLETED	Evaluation of Fanconi Syndrome and Cystinosis
NCT00010426	Not specified	COMPLETED	Randomized Study of New Formulation Ophthalmic Cysteamine Hydrochloride for Corneal Cystine Accumulation in Patients With Cystinosis
NCT00071903	Not specified	COMPLETED	The Role of Susceptibility to Thrombosis in the Pseudotumor Cerebri of Nephropathic Cystinosis: A Case-Control Study
NCT00074516	Not specified	COMPLETED	Kidney Transplantation in Patients With Cystinosis
NCT00100204	Not specified	COMPLETED	Salivary Proteins in Disease and Health
NCT00359684	Not specified	RECRUITING	Use of Cysteamine in the Treatment of Cystinosis
NCT00822250	Not specified	COMPLETED	Clinical and Biological Study of Sub-pigmentation During Infantile Cystinosis
NCT01327807	Not specified	UNKNOWN	Cure Cystinosis International Registry
NCT01432561	Not specified	COMPLETED	Study in Healthy Adults to Determine the Effect That Food Has on the Absorption and Delivery of the Drug Cystagon™
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02012114	Not specified	COMPLETED	A Cohort of Patients With Cystinosis : Compliance to Cysteamine and Neurological Complications
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04071548	Not specified	COMPLETED	The Effect of Exercise on Muscle Dysfunction in Cystinosis
NCT05146830	Not specified	ENROLLING_BY_INVITATION	A Long-Term Follow-Up Study of Participants With Cystinosis Who Previously Received CTNS-RD-04
NCT05545774	Not specified	COMPLETED	Neuromuscular Characterisation in Late Adolescent and Adult Cystinosis Patients
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05843851	Not specified	RECRUITING	Genetic Newborn Screening for Cystinosis and Primary Hyperoxaluria
NCT05901077	Not specified	RECRUITING	European Cystinosis Cohort
NCT05959668	Not specified	RECRUITING	Development of Health-related Quality of Life Instrument for Patients With Cystinosis
NCT06027385	Not specified	COMPLETED	Genetic Newborn Screening for Cystinosis and Spinal Muscular Atrophy
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT07319091	Not specified	NOT_YET_RECRUITING	Cystinosis and Mitochondrial Metabolism