CISD1

Summary

CISD1 (CDGSH iron sulfur domain 1, HGNC:30880) is a protein-coding gene on chromosome 10q21.1, encoding CDGSH iron-sulfur domain-containing protein 1 (Q9NZ45). L-cysteine transaminase that catalyzes the reversible transfer of the amino group from L-cysteine to the alpha-keto acid 2-oxoglutarate to respectively form 2-oxo-3-sulfanylpropanoate and L-glutamate.

This gene encodes a protein with a CDGSH iron-sulfur domain and has been shown to bind a redox-active [2Fe-2S] cluster. The encoded protein has been localized to the outer membrane of mitochondria and is thought to play a role in regulation of oxidation. Genes encoding similar proteins are located on chromosomes 4 and 17, and a pseudogene of this gene is located on chromosome 2.

Source: NCBI Gene 55847 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 24 total
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018464

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30880
Approved symbol	CISD1
Name	CDGSH iron sulfur domain 1
Location	10q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MDS029, mitoNEET
Ensembl gene	ENSG00000122873
Ensembl biotype	protein_coding
OMIM	611932
Entrez	55847

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000333926, ENST00000464703, ENST00000488388, ENST00000489785, ENST00000865195, ENST00000948691

RefSeq mRNA: 1 — MANE Select: NM_018464 NM_018464

CCDS: CCDS7251

Canonical transcript exons

ENST00000333926 — 3 exons

Exon	Start	End
ENSE00001339759	58287561	58289586
ENSE00001923243	58269162	58269304
ENSE00003585757	58277117	58277322

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.0597 / max 488.0229, expressed in 1811 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104984	45.5104	1809
104983	2.5221	1300
104985	0.0272	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	99.32	gold quality
superior vestibular nucleus	UBERON:0007227	99.13	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.05	gold quality
substantia nigra pars compacta	UBERON:0001965	99.02	gold quality
body of tongue	UBERON:0011876	99.00	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.89	gold quality
renal medulla	UBERON:0000362	98.82	gold quality
dorsal root ganglion	UBERON:0000044	98.74	gold quality
ventral tegmental area	UBERON:0002691	98.65	gold quality
vena cava	UBERON:0004087	98.65	gold quality
oocyte	CL:0000023	98.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.24	gold quality
lateral globus pallidus	UBERON:0002476	98.13	gold quality
saphenous vein	UBERON:0007318	97.93	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.90	gold quality
pharyngeal mucosa	UBERON:0000355	97.85	gold quality
parietal lobe	UBERON:0001872	97.83	gold quality
left ventricle myocardium	UBERON:0006566	97.83	gold quality
superior surface of tongue	UBERON:0007371	97.81	gold quality
pericardium	UBERON:0002407	97.70	gold quality
postcentral gyrus	UBERON:0002581	97.58	gold quality
inferior vagus X ganglion	UBERON:0005363	97.50	gold quality
tongue	UBERON:0001723	97.44	gold quality
jejunum	UBERON:0002115	97.43	gold quality
cardiac ventricle	UBERON:0002082	97.37	gold quality
heart left ventricle	UBERON:0002084	97.37	gold quality
medulla oblongata	UBERON:0001896	97.34	gold quality
trigeminal ganglion	UBERON:0001675	97.31	gold quality
duodenum	UBERON:0002114	97.30	gold quality
right atrium auricular region	UBERON:0006631	97.28	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	15.87
E-HCAD-25	yes	11.74
E-GEOD-125970	yes	4.55
E-GEOD-83139	no	2.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting CISD1, 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-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-1299	99.77	71.24	2389

Literature-anchored findings (GeneRIF, showing 38)

• mito- NEET is an important iron-containing protein involved in the control of maximal mitochondrial respiratory rates (PMID:17376863)
• Spectroscopic studies show that the 2Fe-2S cluster is coordinated by Cys-3 and His-1. The His ligand is shown to be involved in the observed pH lability of the cluster, indicating that loss of this ligand via protonation triggered release of the cluster. (PMID:17584744)
• Crystal structure of mitoNEET reveals distinct groups of iron sulfur proteins. (PMID:17766439)
• biophysical properties of mitoNEET suggest that it may participate in a redox-sensitive signaling and/or in Fe-S cluster transfer (PMID:17766440)
• X-ray crystallographic studies show that mitoNEET dimer may interact with other proteins via the surface residues in close proximity to the [2Fe-2S] cluster (PMID:17905743)
• A CISD1-GFP chimera was found to be located into mitochondria. (PMID:18047834)
• The physiologically relevant acid ionization constant (pKa) of histidine residues makes histidine87 a likely candidate for modulating the lability of the metal cluster in mitoNEET. (PMID:19388667)
• There is considerable flexibility in the position of the cytoplasmic tethering arms, resulting in two different conformations in the crystal structure of mitoNEET. (PMID:19574633)
• We use electron paramagnetic resonance spectroscopy to investigate the [2Fe-2S]cluster in mitoNEET. (PMID:20099820)
• Reduced nicotinamide adenine dinucleotide phosphate (NADPH) can bind to homodimeric mitoNEET, influencing the stability of the [2Fe-2S] cluster that is bound within a loop region (Y71-H87) in each subunit. (PMID:20932062)
• Results describe the folding landscape of mitoNEET, and uncover communication between distal regions of the protein. (PMID:21402934)
• Results describe the discovery of potential mitoNEET ligand binding sites and novel ligands, and suggests the possibility for detailed structural studies of mitoNEET-ligand complexes. (PMID:21531159)
• The iron-sulfur cluster-containing protein mitoNEET interacts with two potentially redox active substances at the surface of mitochondria; mitoNEET forms complexes with resveratrol-3-sulfate, a primary metabolite of the natural product resveratrol. (PMID:21591687)
• crystal structure of H87C mitoNEET was determined to 1.7 A resolution (R factor = 18%) to investigate the structural basis of the changes in the properties of the 2Fe-2S cluster (PMID:21636891)
• These findings suggest a likely role for mNT in [2Fe-2S] and/or iron transfer to acceptor proteins. (PMID:21788481)
• NADPH can regulate both mitoNEET [2Fe-2S] cluster levels in the cell as well as the ability of the protein to transfer [2Fe-2S] clusters to cytosolic or mitochondrial acceptors. (PMID:22351774)
• a loop (L2) 20 A away from the metal center exerts allosteric control over the cluster binding domain and regulates multiple properties of the metal center. Mutagenesis of L2 results in significant shifts in the redox potential of the [2Fe-2S] cluster. (PMID:23271805)
• Data show that the protein levels of NAF-1 (CISD2) and mNT (CISD1) are elevated in human epithelial breast cancer cells. (PMID:23959881)
• The MitoNEET forms a covalent complex with GDH1 through disulfide bond formation and acts as an activator. (PMID:24295216)
• pioglitazone may modulate the function of mitoNEET by blocking the thiol-mediated reduction of [2Fe-2S] clusters in the protein. (PMID:24403080)
• In this review, we evaluate the current understanding regarding how mitoNEET regulates cellular bioenergetics as well as the structural requirements for drug compound association with mitoNEET (PMID:24814435)
• MitoNEET governs a novel trafficking pathway to rebuild an Fe-S cluster into cytosolic aconitase/IRP1. (PMID:25012650)
• SNPs in three genes CYP26B1 rs2241057, CISD1 rs2251039, rs2590370, and TBX1 rs4819522 were involved in six potential pathways to influence serum prostate-specific antigen levels. (PMID:25168891)
• Studies indicate that NEET proteins are associated with diseases including cancer and diabetes. (PMID:25448035)
• Glutathione reductase reduces mitochondrial protein mitoNEET [2Fe-2S] clusters. (PMID:25645953)
• A possible role of CISD1 in obesity-associated dysfunctional adipogenesis in human visceral adipose tissue. (PMID:26692580)
• Our results confirm the observation that mitoNEET is important in transferring the iron sulfur clusters to the cytosolic aconitase in living cells and the His-87 ligand in mitoNEET plays important role in this process. (PMID:26778000)
• the redox-sensing function of mNT is a key component of the cellular adaptive response to help stress-sensitive Fe-S proteins recover from oxidative injury. (PMID:26887944)
• CISD1 inhibits ferroptosis by protecting the cells against mitochondrial lipid peroxidation. (PMID:27510639)
• The results suggest that flavin nucleotides may act as electron shuttles to reduce the mitoNEET [2Fe-2S] clusters and regulate mitochondrial functions in human cells. (PMID:27923678)
• Data suggest that, compared with oxygen, ubiquinone-2 is more efficient in oxidizing mitoNEET [2Fe-2S] clusters, suggesting that ubiquinone could be an intrinsic electron acceptor of reduced mitoNEET [2Fe-2S] clusters in mitochondrial outer membrane. (PMID:28461337)
• The [2Fe-2S] clusters of mitoNEET are reduced via the formation of a transient complex that brings the [2Fe-2S] clusters of mitoNEET close to the redox-active [2Fe-2S] cluster of anamorsin. (PMID:28648056)
• mitoNEET regulates VDAC in a redox-dependent manner in cells, closing the pore and likely disrupting VDAC’s flow of metabolites (PMID:31527235)
• Defects in CISD-1, a mitochondrial iron-sulfur protein, lower glucose level and ATP production in Caenorhabditis elegans. (PMID:32200954)
• Exploring the FMN binding site in the mitochondrial outer membrane protein mitoNEET. (PMID:32445867)
• CISD1 Is a Breast Cancer Prognostic Biomarker Associated with Diabetes Mellitus. (PMID:36671422)
• Overexpression of ferroptosis-related genes FSP1 and CISD1 is related to prognosis and tumor immune infiltration in gastric cancer. (PMID:36995520)
• Regulations of mitoNEET by the key redox homeostasis molecule glutathione. (PMID:38527404)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cisd1	ENSDARG00000079516
mus_musculus	Cisd1	ENSMUSG00000037710
rattus_norvegicus	Cisd1	ENSRNOG00000000610
drosophila_melanogaster	Cisd2	FBGN0062442
caenorhabditis_elegans		WBGENE00044026

Paralogs (2): CISD2 (ENSG00000145354), CISD3 (ENSG00000277972)

Protein

Protein identifiers

CDGSH iron-sulfur domain-containing protein 1 — Q9NZ45 (reviewed: Q9NZ45)

Alternative names: Cysteine transaminase CISD1, MitoNEET

All UniProt accessions (1): Q9NZ45

UniProt curated annotations — full annotation on UniProt →

Function. L-cysteine transaminase that catalyzes the reversible transfer of the amino group from L-cysteine to the alpha-keto acid 2-oxoglutarate to respectively form 2-oxo-3-sulfanylpropanoate and L-glutamate. The catalytic cycle occurs in the presence of pyridoxal 5’-phosphate (PLP) cofactor that facilitates transamination by initially forming an internal aldimine with the epsilon-amino group of active site Lys-55 residue on the enzyme (PLP-enzyme aldimine), subsequently displaced by formation of an external aldimine with the substrate amino group (PLP-L-cysteine aldimine). The external aldimine is further deprotonated to form a carbanion intermediate, which in the presence of 2-oxoglutarate regenerates PLP yielding final products 2-oxo-3-sulfanylpropanoate and L-glutamate. The proton transfer in carbanion intermediate is suggested to be controlled by the active site lysine residue, whereas PLP stabilizes carbanion structure through electron delocalization, also known as the electron sink effect. Plays a key role in regulating maximal capacity for electron transport and oxidative phosphorylation. May be involved in iron-sulfur cluster shuttling and/or in redox reactions. Can transfer the [2Fe-2S] cluster to an apo-acceptor protein only when in the oxidation state, likely serving as a redox sensor that regulates mitochondrial iron-sulfur cluster assembly and iron trafficking upon oxidative stress.

Subunit / interactions. Homodimer.

Subcellular location. Mitochondrion outer membrane.

Tissue specificity. Expression is reduced in cells derived from cystic fibrosis patients.

Post-translational modifications. Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.

Cofactor. Binds 1 [2Fe-2S] cluster per subunit. The [2Fe-2S] cluster is redox-active and pH labile and is significantly less stable at pH 4.5 as compared with pH 7.0.

Induction. Expression is down-regulated by glibenclamide and 5-[(4-carboxyphenyl)methylene]-2-thioxo-3-(3-trifluoromethyl)phenyl-4-thiazolidinone (CFTR(inh)172), and up-regulated by cAMP/isoproterenol/IBMX, components that inhibit and stimulate chloride transport activity respectively.

Miscellaneous. Binds pioglitazone, an anti-diabetes drug. Binding increases the stability of the 2Fe-2S cluster.

Similarity. Belongs to the CISD protein family.

RefSeq proteins (1): NP_060934* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018967	FeS-contain_CDGSH-typ	Domain
IPR019610	FeS-contain_mitoNEET_N	Domain
IPR042216	MitoNEET_CISD	Homologous_superfamily
IPR045131	CISD1/2	Family

Pfam: PF09360, PF10660

Catalyzed reactions (Rhea), 1 shown:

• L-cysteine + 2-oxoglutarate = 2-oxo-3-sulfanylpropanoate + L-glutamate (RHEA:17441)

UniProt features (38 total): cross-link 9, mutagenesis site 9, strand 5, modified residue 4, binding site 4, initiator methionine 1, chain 1, transmembrane region 1, topological domain 1, turn 1, helix 1, active site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
4EZF	X-RAY DIFFRACTION	1.19
4F2C	X-RAY DIFFRACTION	1.35
3EW0	X-RAY DIFFRACTION	1.4
2QH7	X-RAY DIFFRACTION	1.5
4F28	X-RAY DIFFRACTION	1.55
7P0O	X-RAY DIFFRACTION	1.65
3LPQ	X-RAY DIFFRACTION	1.7
3REE	X-RAY DIFFRACTION	1.76
2R13	X-RAY DIFFRACTION	1.8
2QD0	X-RAY DIFFRACTION	1.81
6DE9	X-RAY DIFFRACTION	1.95
4F1E	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZ45-F1	91.06	0.72

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): 55 (schiff-base intermediate with pyridoxal 5’-phosphate)

Ligand- & substrate-binding residues (4): 72; 74; 83; 87

Post-translational modifications (13): 55, 68, 104, 42, 55, 68, 78, 79, 89, 104, 105, 106, 2

Mutagenesis-validated functional residues (9):

Position	Phenotype
55	slighly reduces the transfer rate of the [2fe-2s] cluster.
55	fully incorporates and stabilizes the [2fe-2s] cluster upon in vitro reconstitution. abolishes alkaline ph dependence of
72	abolishes absorption in the 300-500 nm range.
74	abolishes absorption in the 300-500 nm range.
77	fully incorporates the [2fe-2s] cluster upon in vitro reconstitution. slightly affects neutral ph dependence of the midp
83	abolishes absorption in the 300-500 nm range.
84	fully incorporates the [2fe-2s] cluster upon in vitro reconstitution. does not affect absorption in the 300-500 nm range
87	fully incorporates and stabilizes the [2fe-2s] cluster upon in vitro reconstitution. abolishes alkaline ph dependence of
87	abolishes absorption in the 300-500 nm range.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 250 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, chr10q21, GOLDRATH_ANTIGEN_RESPONSE, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_PROTEIN_MATURATION, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOCC_MITOCHONDRIAL_ENVELOPE, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP

GO Biological Process (4): intracellular iron ion homeostasis (GO:0006879), regulation of autophagy (GO:0010506), regulation of cellular respiration (GO:0043457), protein maturation (GO:0051604)

GO Molecular Function (8): pyridoxal phosphate binding (GO:0030170), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), L-cysteine:2-oxoglutarate transaminase activity (GO:0047801), 2 iron, 2 sulfur cluster binding (GO:0051537), transferase activity (GO:0016740), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020), intracellular membrane-bounded organelle (GO:0043231)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
autophagy	1
regulation of catabolic process	1
regulation of generation of precursor metabolites and energy	1
cellular respiration	1
gene expression	1
protein metabolic process	1
anion binding	1
vitamin B6 binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
amino acid transaminase activity	1
iron-sulfur cluster binding	1
catalytic activity	1
metal cluster binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1
intracellular anatomical structure	1
membrane-bounded organelle	1
intracellular organelle	1

Protein interactions and networks

STRING

1226 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CISD1	CISD3	P0C7P0	991
CISD1	WFS1	O76024	700
CISD1	VDAC1	P21796	642
CISD1	NFS1	Q9Y697	632
CISD1	NCOA4	Q13772	592
CISD1	MNT	Q99583	591
CISD1	IREB2	P48200	583
CISD1	PPARG	P37231	582
CISD1	GPX4	P36969	578
CISD1	TOMM70	O94826	573
CISD1	ACSL4	O60488	571
CISD1	ISCU	Q9H1K1	558
CISD1	ACO1	P21399	547
CISD1	EMC2	Q15006	546
CISD1	LPCAT3	Q6P1A2	538

IntAct

48 interactions, top by confidence:

A	B	Type	Score
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
CISD1	CISD1	psi-mi:“MI:0407”(direct interaction)	0.720
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
OCIAD1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
PTPMT1	TIMM44	psi-mi:“MI:0914”(association)	0.350
NDUFA4	COX7A2L	psi-mi:“MI:0914”(association)	0.350
PTPMT1	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
SH2D3C	TMEM14DP	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
RAB11A	SCAMP1	psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
CISD1	CISD2	psi-mi:“MI:0914”(association)	0.350
ATP2A3	UBXN8	psi-mi:“MI:0914”(association)	0.350
VSIG4	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350

BioGRID (124): CISD1 (Affinity Capture-MS), CISD1 (Affinity Capture-MS), BCAP31 (Co-fractionation), CISD1 (Co-fractionation), CISD1 (Co-fractionation), CISD1 (Co-fractionation), CISD1 (Co-fractionation), CISD1 (Co-fractionation), CISD1 (Co-fractionation), CISD1 (Co-fractionation), CISD1 (Co-fractionation), CISD1 (Co-fractionation), CISD1 (Co-fractionation), CLTC (Co-fractionation), COX4I1 (Co-fractionation)

ESM2 similar proteins: A2XYW4, A7S710, B0K020, B3M1H7, B3MLC5, B3N5N3, B3P5J1, B3RML8, B4GK79, B4GPI0, B4HXL7, B4HZ81, B4JAX0, B4JYJ2, B4K5X8, B4KLC0, B4LRY2, B4MBU8, B4MZ79, B4NFN4, B4NYT3, B4PQ50, B4Q5Z1, B4QZI8, B7PP17, B8ARI7, C1C524, C3YFB4, C3ZWH9, C4A0P0, C4WXC1, P0CR50, P0CR51, Q05B71, Q29BX8, Q29P70, Q3ZBU2, Q4V7N8, Q5I027, Q6AZG1

Diamond homologs: B0K020, B3M1H7, B3P5J1, B3RML8, B4GPI0, B4HZ81, B4JYJ2, B4K5X8, B4MBU8, B4NFN4, B4PQ50, B4QZI8, B5X8S2, B9EPI1, C1BGG0, C1BI29, C1C524, C3ZWH9, C4A0P0, Q05B71, Q29BX8, Q3ZBU2, Q5I027, Q6AZG1, Q6PCF8, Q7T326, Q8N5K1, Q91WS0, Q9CQB5, Q9FLI7, Q9NZ45, Q9VAM6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

443 predictions. Top by Δscore:

Variant	Effect	Δscore
10:58269296:GC:G	donor_gain	1.0000
10:58277109:T:A	acceptor_gain	1.0000
10:58277114:TA:T	acceptor_loss	1.0000
10:58277115:A:AG	acceptor_gain	1.0000
10:58277115:AGTT:A	acceptor_gain	1.0000
10:58277116:G:GC	acceptor_gain	1.0000
10:58277116:GT:G	acceptor_gain	1.0000
10:58277116:GTT:G	acceptor_gain	1.0000
10:58277116:GTTG:G	acceptor_gain	1.0000
10:58277116:GTTGA:G	acceptor_gain	1.0000
10:58277320:AAGGT:A	donor_loss	1.0000
10:58277321:AGGTG:A	donor_loss	1.0000
10:58277324:T:A	donor_loss	1.0000
10:58277329:A:T	donor_gain	1.0000
10:58287559:A:AG	acceptor_gain	1.0000
10:58287560:G:GA	acceptor_gain	1.0000
10:58269307:G:GT	donor_gain	0.9900
10:58276220:T:G	donor_gain	0.9900
10:58277323:G:GG	donor_gain	0.9900
10:58287555:TCCTA:T	acceptor_loss	0.9900
10:58287556:CCTA:C	acceptor_loss	0.9900
10:58287557:CTA:C	acceptor_loss	0.9900
10:58287558:TA:T	acceptor_loss	0.9900
10:58287559:A:C	acceptor_loss	0.9900
10:58287560:GTT:G	acceptor_gain	0.9900
10:58287560:GTTC:G	acceptor_gain	0.9900
10:58287560:GTTCC:G	acceptor_gain	0.9900
10:58287682:TCGTG:T	donor_gain	0.9900
10:58287686:G:GT	donor_gain	0.9900
10:58269303:AGGTG:A	donor_loss	0.9800

AlphaMissense

719 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:58277299:T:C	C72R	1.000
10:58277299:T:A	C72S	0.999
10:58277300:G:A	C72Y	0.999
10:58277300:G:C	C72S	0.999
10:58277300:G:T	C72F	0.999
10:58277301:C:G	C72W	0.999
10:58277305:T:A	C74S	0.999
10:58277305:T:C	C74R	0.999
10:58277306:G:C	C74S	0.999
10:58277308:T:A	W75R	0.999
10:58277308:T:C	W75R	0.999
10:58287561:T:C	F80L	0.999
10:58287563:C:A	F80L	0.999
10:58287563:C:G	F80L	0.999
10:58287570:T:A	C83S	0.999
10:58287570:T:C	C83R	0.999
10:58287571:G:A	C83Y	0.999
10:58287571:G:C	C83S	0.999
10:58287571:G:T	C83F	0.999
10:58287582:C:G	H87D	0.999
10:58287584:C:A	H87Q	0.999
10:58287584:C:G	H87Q	0.999
10:58287619:G:A	G99D	0.999
10:58287625:T:C	L101P	0.999
10:58277302:C:A	R73S	0.998
10:58277306:G:A	C74Y	0.998
10:58277307:T:G	C74W	0.998
10:58277310:G:C	W75C	0.998
10:58277310:G:T	W75C	0.998
10:58277315:C:T	S77F	0.998

dbSNP variants (sampled 300 via entrez): RS1000128393 (10:58267738 T>G), RS1000188601 (10:58273704 G>T), RS1000353602 (10:58288773 T>C), RS1000467390 (10:58280815 T>C,G), RS1000507927 (10:58283302 T>C), RS1000573994 (10:58281771 C>G,T), RS1000744099 (10:58268126 G>A,C), RS1000943302 (10:58283605 G>A), RS1000957353 (10:58286219 AAG>A), RS1001074962 (10:58268332 C>A,G,T), RS1001140134 (10:58276038 A>T), RS1001161937 (10:58272499 T>A), RS1001401493 (10:58278788 G>A,T), RS1001420863 (10:58269455 C>T), RS1001515697 (10:58287869 G>C,T)

Disease associations

OMIM: gene MIM:611932 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001725_1	Inflammatory bowel disease	8.000000e-09
GCST004131_118	Inflammatory bowel disease	1.000000e-06
GCST004132_81	Crohn’s disease	6.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795168 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,213,445 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1201288	DANTROLENE	4	10,182
CHEMBL121	ROSIGLITAZONE	4	58,849
CHEMBL1551	URSODIOL	4	22,553
CHEMBL35	FUROSEMIDE	4	224,045
CHEMBL457	GEMFIBROZIL	4	35,238
CHEMBL472	GLYBURIDE	4	53,236
CHEMBL53463	DOXORUBICIN	4	314,282
CHEMBL572	NITROFURANTOIN	4	26,231
CHEMBL595	PIOGLITAZONE	4	57,130
CHEMBL140	CURCUMIN	3	93,882
CHEMBL231616	TRIAPINE	3	4,524
CHEMBL14249	ADENOSINE TRIPHOSPHATE	2	287,353
CHEMBL150	KAEMPFEROL	1	25,940

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

ChEMBL bioactivities

111 potent at pChembl≥5 of 153 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	Ki	6	nM	CHEMBL3979616
7.66	Ki	22	nM	CHEMBL3893332
7.54	Ki	29	nM	CHEMBL3970270
7.51	Ki	31	nM	ROSIGLITAZONE
7.48	Ki	33	nM	CHEMBL230515
7.44	Ki	36	nM	CHEMBL3890124
7.43	Ki	37	nM	CHEMBL496587
7.41	Ki	39	nM	CHEMBL3948168
7.40	Ki	40	nM	CHEMBL3959175
7.34	Ki	46	nM	CHEMBL2348829
7.28	Ki	52	nM	CHEMBL3909388
7.22	Ki	60	nM	CHEMBL3924991
7.13	Ki	74	nM	CHEMBL255822
7.11	Ki	77	nM	CHEMBL2218926
7.11	Ki	78	nM	CHEMBL305695
7.08	Ki	84	nM	CHEMBL2018126
7.00	Ki	101	nM	CURCUMIN
6.90	Ki	125	nM	CHEMBL3956710
6.88	Ki	132	nM	KAEMPFEROL
6.87	Ki	136	nM	CHEMBL224467
6.86	Ki	139	nM	CHEMBL3976274
6.85	Ki	141	nM	CHEMBL3967845
6.85	Ki	141	nM	CHEMBL3891346
6.85	Ki	141	nM	CHEMBL3982310
6.84	Ki	144	nM	CHEMBL1208633
6.84	Ki	145	nM	TRYPROSTATIN A
6.83	IC50	148	nM	CHEMBL3979616
6.83	Ki	148	nM	CHEMBL3945250
6.78	Ki	165	nM	CHEMBL3927255
6.72	Ki	191	nM	CHEMBL3930279
6.67	Ki	213	nM	CHEMBL380899
6.65	Ki	224	nM	CHEMBL1823804
6.59	Ki	255	nM	CHEMBL3938874
6.53	Ki	297	nM	CHEMBL183906
6.50	Ki	315	nM	CHEMBL602048
6.47	Ki	341	nM	CHEMBL3917957
6.43	Ki	370	nM	PIOGLITAZONE
6.41	Ki	388	nM	TRIAPINE
6.39	Ki	409	nM	CHEMBL1823802
6.38	Ki	412	nM	CHEMBL3967264
6.38	Ki	413	nM	CHEMBL3936343
6.33	Ki	472	nM	CHEMBL3929569
6.29	IC50	518	nM	CHEMBL3893332
6.24	Ki	570	nM	CHEMBL1823803
6.23	Ki	583	nM	CHEMBL3901608
6.22	Ki	598	nM	GLITAZONE
6.19	Ki	646	nM	CHEMBL500110
6.16	IC50	686.1	nM	CHEMBL3970270
6.14	IC50	731	nM	ROSIGLITAZONE
6.11	IC50	770.1	nM	CHEMBL230515

PubChem BioAssay actives

111 with measured affinity, of 222 total; 50 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
(2E)-6-hydroxy-2-[(2-hydroxyphenyl)methylidene]-1-benzofuran-3-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0060	uM
(5E)-5-[[3-methoxy-4-[(4-methylphenyl)methoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0220	uM
(5E)-5-[[4-[3-(4-ethylphenoxy)propoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0290	uM
Rosiglitazone	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0310	uM
(5E)-5-[(3-methoxy-4-phenylmethoxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0330	uM
(5E)-5-[[4-[2-(2-chlorophenoxy)ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0360	uM
(5Z)-5-[(3-bromophenyl)methylidene]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0370	uM
(2E)-2-[[4-(dimethylamino)phenyl]methylidene]-6-hydroxy-1-benzofuran-3-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0390	uM
(5E)-5-[[3-chloro-4-[(4-fluorophenyl)methoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0400	uM
(5Z)-5-[(3-bromophenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0460	uM
(2E)-2-[[4-(dimethylamino)phenyl]methylidene]-1-benzofuran-3-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0520	uM
(5E)-5-[[4-[3-(2-chlorophenoxy)propoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0600	uM
(5Z)-5-[(4-hydroxy-3-methoxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0740	uM
2-[(3-bromo-5-tert-butyl-4-hydroxyphenyl)methylidene]propanedinitrile	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0770	uM
2-[(4-hydroxyphenyl)methylidene]propanedinitrile	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0780	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.0840	uM
Curcumin	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1010	uM
(5Z)-5-[(2,5-dibromo-4-chlorophenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1250	uM
3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1320	uM
(5Z)-5-[(4-bromophenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1360	uM
(5Z)-5-(quinoxalin-5-ylmethylidene)-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1390	uM
(5Z)-5-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1410	uM
(5Z)-2-sulfanylidene-5-[[3-(trifluoromethyl)phenyl]methylidene]-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1410	uM
1-(4,5-dimethyl-1,3-thiazol-2-yl)-2-(furan-2-yl)-4-hydroxy-3-(7-methoxy-2,3-dihydro-1-benzofuran-2-carbonyl)-2H-pyrrol-5-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1410	uM
[3-hydroxy-5-[(E)-2-(4-hydroxyphenyl)ethenyl]phenyl] hydrogen sulfate	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1440	uM
(3S,8aS)-3-[[6-methoxy-2-(3-methylbut-2-enyl)-1H-indol-3-yl]methyl]-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1450	uM
N-(2-phenylcyclopropyl)piperidin-4-amine	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1480	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1650	uM
(5Z)-5-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.1910	uM
(5Z)-5-[(4-chlorophenyl)methylidene]-3-methyl-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.2130	uM
5-[(2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.2240	uM
(5Z)-5-(pyridin-4-ylmethylidene)-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.2550	uM
(5Z)-5-[[3-(trifluoromethyl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.2970	uM
5-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.3150	uM
N-[(5E)-5-[[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]methylidene]-4-oxo-1,3-thiazol-2-yl]acetamide	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.3410	uM
Pioglitazone	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.3700	uM
[(E)-(3-amino-2-pyridinyl)methylideneamino]thiourea	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.3880	uM
5-[(4-hydroxy-3,5-dimethylphenyl)methyl]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.4090	uM
3-[(5Z)-5-benzylidene-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]propanoic acid	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.4120	uM
1-hydroxy-4-oxido-3-(4-phenoxyphenyl)quinoxalin-4-ium-2-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.4130	uM
(2Z)-2-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)-N-phenylacetamide	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.4720	uM
5-[(3,5-dimethylphenyl)methyl]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.5700	uM
(2Z)-N-(3-hydroxyphenyl)-2-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)acetamide	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.5830	uM
5-[(4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.5980	uM
(5Z)-5-benzylidene-3-methyl-2-sulfanylidene-1,3-thiazolidin-4-one	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.6460	uM
Nitrofurantoin	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.8160	uM
(5Z)-3-propyl-5-(pyridin-4-ylmethylidene)-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.8310	uM
(5E)-5-[(3-bromophenyl)methylidene]-1,3-thiazolidine-2,4-dione	616421: Displacement of [3H]-rosiglitazone from human recombinant C-terminal His-tagged cytosolic domain of mitoNEET (32-108) by scintillation proximity assay	ic50	0.8600	uM
(5Z)-5-(pyridin-4-ylmethylidene)-1,3-thiazolidine-2,4-dione	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	0.9520	uM
ursodiol	1323835: Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis	ki	1.1340	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
bisphenol A	decreases expression, increases expression	2
Doxorubicin	affects expression	2
Particulate Matter	decreases expression, increases abundance	2
dicrotophos	decreases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
deguelin	increases expression	1
corosolic acid	decreases expression	1
K 7174	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
dorsomorphin	affects cotreatment, increases expression	1
picoxystrobin	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Coumestrol	increases expression	1
Diethylstilbestrol	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Dinitrochlorobenzene	decreases expression	1
Estradiol	increases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1826572	Binding	Displacement of [3H]-rosiglitazone from human recombinant C-terminal His-tagged cytosolic domain of mitoNEET (32-108) by scintillation proximity assay	A novel binding assay identifies high affinity ligands to the rosiglitazone binding site of mitoNEET. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1NF	Abcam HeLa CISD1 KO	Cancer cell line	Female
CVCL_D7ML	Ubigene A-549 CISD1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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