MDN1

Summary

MDN1 (midasin AAA ATPase 1, HGNC:18302) is a protein-coding gene on chromosome 6q15, encoding Midasin (Q9NU22). Nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

Predicted to enable ATP binding activity and ATP hydrolysis activity. Involved in ribosomal large subunit assembly. Located in cytosol; intermediate filament cytoskeleton; and nuclear lumen.

Source: NCBI Gene 23195 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 917 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_014611

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18302
Approved symbol	MDN1
Name	midasin AAA ATPase 1
Location	6q15
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0301, Rea1
Ensembl gene	ENSG00000112159
Ensembl biotype	protein_coding
OMIM	618200
Entrez	23195

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 18 retained_intron, 9 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000369393, ENST00000439638, ENST00000468568, ENST00000487831, ENST00000700640, ENST00000700641, ENST00000700642, ENST00000700643, ENST00000700644, ENST00000700645, ENST00000700646, ENST00000700647, ENST00000700648, ENST00000700649, ENST00000700650, ENST00000700651, ENST00000700652, ENST00000700653, ENST00000700654, ENST00000700655, ENST00000700672, ENST00000700673, ENST00000700674, ENST00000700675, ENST00000700676, ENST00000700677, ENST00000700678, ENST00000700679

RefSeq mRNA: 1 — MANE Select: NM_014611 NM_014611

CCDS: CCDS5024

Canonical transcript exons

ENST00000369393 — 102 exons

Exon	Start	End
ENSE00001084637	89758255	89758351
ENSE00001084638	89761645	89761748
ENSE00001084639	89751431	89751582
ENSE00001084640	89753512	89753622
ENSE00001084641	89754083	89754230
ENSE00001084642	89749543	89749751
ENSE00001084643	89750354	89750532
ENSE00001084644	89762319	89762530
ENSE00001084645	89756277	89756390
ENSE00001084646	89758816	89758960
ENSE00001084648	89789780	89789911
ENSE00001084649	89780212	89780293
ENSE00001084650	89774621	89774733
ENSE00001084651	89781399	89781592
ENSE00001084652	89776600	89776695
ENSE00001242807	89771561	89771621
ENSE00001242815	89772573	89772721
ENSE00001242848	89785012	89785126
ENSE00001242856	89787854	89787957
ENSE00001242869	89790159	89790401
ENSE00001242878	89793762	89793954
ENSE00001242885	89794100	89794207
ENSE00001242891	89794577	89794801
ENSE00001242898	89803328	89803554
ENSE00001897633	89642498	89644193
ENSE00002209564	89694074	89694183
ENSE00002210476	89686902	89687023
ENSE00002210864	89745492	89745626
ENSE00002211847	89656700	89656801
ENSE00002212218	89699601	89699727
ENSE00002213391	89689870	89690143
ENSE00002213573	89688573	89688808
ENSE00002214050	89673236	89673462
ENSE00002214378	89661431	89661578
ENSE00002215199	89732557	89732775
ENSE00002220651	89728931	89729139
ENSE00002223882	89695605	89695992
ENSE00002223900	89727833	89727955
ENSE00002224864	89707361	89707476
ENSE00002225310	89687344	89687438
ENSE00002228255	89692443	89693148
ENSE00002228411	89655764	89655968
ENSE00002229131	89723512	89723619
ENSE00002233253	89712036	89712256
ENSE00002234720	89652192	89652281
ENSE00002235593	89708496	89708628
ENSE00002235830	89722955	89723143
ENSE00002236013	89670919	89671080
ENSE00002236600	89674104	89674589
ENSE00002237178	89740234	89740378
ENSE00002237319	89718767	89719030
ENSE00002238686	89712575	89712786
ENSE00002239117	89684876	89684985
ENSE00002240521	89677570	89677696
ENSE00002243739	89725199	89725396
ENSE00002246051	89658610	89658917
ENSE00002250105	89713148	89713296
ENSE00002251238	89745273	89745411
ENSE00002253366	89698865	89699035
ENSE00002254209	89662792	89662967
ENSE00002257381	89710681	89710794
ENSE00002259071	89743150	89743280
ENSE00002260496	89646540	89646603
ENSE00002261942	89652992	89653155
ENSE00002262480	89747329	89747470
ENSE00002265142	89648032	89648146
ENSE00002265240	89683132	89683330
ENSE00002265904	89654164	89654334
ENSE00002266504	89701558	89701678
ENSE00002268839	89701904	89702061
ENSE00002269198	89650732	89650847
ENSE00002269579	89645015	89645157
ENSE00002272439	89658209	89658370
ENSE00002273209	89668014	89668151
ENSE00002280445	89675464	89675579
ENSE00002283358	89715653	89715769
ENSE00002285391	89672200	89672363
ENSE00002288631	89700646	89700856
ENSE00002291554	89678599	89678745
ENSE00002293683	89714543	89714751
ENSE00002296532	89690673	89690834
ENSE00002298428	89680589	89680751
ENSE00002300536	89662087	89662239
ENSE00002305739	89648256	89648329
ENSE00002306980	89716650	89716809
ENSE00002309369	89696360	89696574
ENSE00002310266	89719136	89719225
ENSE00002310532	89743576	89743714
ENSE00002311005	89700063	89700294
ENSE00002313422	89676102	89676207
ENSE00002314839	89730726	89730923
ENSE00002315097	89688078	89688173
ENSE00002315134	89664487	89664628
ENSE00002316902	89738326	89738455
ENSE00002316951	89683831	89683904
ENSE00002317736	89672547	89672702
ENSE00002322848	89685827	89685973
ENSE00002323161	89706059	89706192
ENSE00002323261	89650024	89650198
ENSE00002323333	89718366	89718627
ENSE00003786698	89749223	89749369
ENSE00003846986	89819506	89819794

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.4299 / max 313.2340, expressed in 1792 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74713	20.4299	1792

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	93.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.10	gold quality
cerebellar hemisphere	UBERON:0002245	92.59	gold quality
cerebellar cortex	UBERON:0002129	92.56	gold quality
cerebellum	UBERON:0002037	92.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.19	gold quality
nucleus accumbens	UBERON:0001882	92.07	gold quality
putamen	UBERON:0001874	91.86	gold quality
lower esophagus mucosa	UBERON:0035834	91.73	gold quality
primary visual cortex	UBERON:0002436	91.67	gold quality
caudate nucleus	UBERON:0001873	91.43	gold quality
hypothalamus	UBERON:0001898	91.40	gold quality
substantia nigra	UBERON:0002038	91.40	gold quality
right testis	UBERON:0004534	90.74	gold quality
Ammon’s horn	UBERON:0001954	90.70	gold quality
amygdala	UBERON:0001876	90.62	gold quality
temporal lobe	UBERON:0001871	90.47	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.46	gold quality
right frontal lobe	UBERON:0002810	90.40	gold quality
apex of heart	UBERON:0002098	90.30	gold quality
anterior cingulate cortex	UBERON:0009835	90.29	gold quality
liver	UBERON:0002107	90.22	gold quality
brain	UBERON:0000955	90.17	gold quality
sural nerve	UBERON:0015488	90.13	gold quality
left testis	UBERON:0004533	90.05	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.82	gold quality
testis	UBERON:0000473	89.76	gold quality
left lobe of thyroid gland	UBERON:0001120	89.75	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.74	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting MDN1, 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-513A-5P	100.00	69.77	2465
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-95-5P	99.89	72.17	3973

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 1)

• the crystal structure of the UBL domain of the WDR12 homologue from S. cerevisiae at 1.7 A resolution is reported and demonstrated that human midasin binds to WDR12 as well as Nle1 through their respective UBL domains. (PMID:26601951)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mdn1	ENSDARG00000008976
mus_musculus	Mdn1	ENSMUSG00000058006
rattus_norvegicus	Mdn1	ENSRNOG00000047513
drosophila_melanogaster	CG13185	FBGN0033661
caenorhabditis_elegans		WBGENE00018898

Paralogs (3): SAMD15 (ENSG00000100583), IWS1 (ENSG00000163166), TCHHL1 (ENSG00000182898)

Protein

Protein identifiers

Midasin — Q9NU22 (reviewed: Q9NU22)

Alternative names: Dynein-related AAA-ATPase MDN1, MIDAS-containing protein

All UniProt accessions (1): Q9NU22

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits. Functions at successive maturation steps to remove ribosomal factors at critical transition points, first driving the exit of early pre-60S particles from the nucleolus and then driving late pre-60S particles from the nucleus. At an early stage in 60S maturation, mediates the dissociation of the PeBoW complex (PES1-BOP1-WDR12) from early pre-60S particles, rendering them competent for export from the nucleolus to the nucleoplasm. Subsequently recruited to the nucleoplasmic particles through interaction with SUMO-conjugated PELP1 complex. This binding is only possible if the 5S RNP at the central protuberance has undergone the rotation to complete its maturation.

Subunit / interactions. Associates with pre-60S ribosomes in the nucleoplasm. Interacts (via its hexameric AAA ATPase ring) with the PELP1 complex (via PELP1); the interaction is regulated by SUMO conjugation of PELP1 and is crucial for recruitment of MDN1 to the pre-ribosomal particle. Interacts (via VWFA/MIDAS domain) with WDR12 (via UBL domain). Interacts (via VWFA/MIDAS domain) with NLE1 (via UBL domain).

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Cytoplasm.

Similarity. Belongs to the midasin family.

RefSeq proteins (1): NP_055426* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR003593	AAA+_ATPase	Domain
IPR011704	ATPase_dyneun-rel_AAA	Domain
IPR012099	Midasin	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR040848	AAA_lid_7	Domain
IPR041190	Midasin_AAA_lid_5	Domain
IPR048617	MDN1_AAA_lid_4	Domain

Pfam: PF07728, PF17865, PF17867, PF21108

UniProt features (68 total): compositionally biased region 21, sequence variant 15, modified residue 13, region of interest 11, binding site 6, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8QL1	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

No AlphaFold model available for Q9NU22 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Ligand- & substrate-binding residues (6): 329–336; 677–684; 1084–1091; 1390–1397; 1753–1760; 2066–2073

Post-translational modifications (13): 1, 1177, 1683, 1754, 4212, 4538, 4752, 4754, 4889, 4898, 4937, 4946, 5015

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 201 (showing top): chr6q15, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_RIBOSOME_BIOGENESIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_RIBOSOME_ASSEMBLY, GOBP_RIBOSOMAL_LARGE_SUBUNIT_ASSEMBLY, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_MATURATION_OF_LSU_RRNA, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_MATURATION_OF_5_8S_RRNA

GO Biological Process (2): ribosomal large subunit assembly (GO:0000027), ribosome biogenesis (GO:0042254)

GO Molecular Function (4): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), membrane (GO:0016020), intermediate filament cytoskeleton (GO:0045111), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nuclear lumen	2
protein-RNA complex assembly	1
ribosome assembly	1
ribosomal large subunit biogenesis	1
ribonucleoprotein complex biogenesis	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
cytoskeleton	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MDN1	WDR12	Q9GZL7	878
MDN1	WDR18	Q9BV38	832
MDN1	GNL2	Q13823	809
MDN1	NSA2	O95478	769
MDN1	RPF2	Q9H7B2	766
MDN1	WDR74	Q6RFH5	763
MDN1	NOL9	Q5SY16	754
MDN1	NMD3	Q96D46	744
MDN1	RSL24D1	Q9UHA3	700
MDN1	LSG1	Q9H089	686
MDN1	NVL	O15381	665
MDN1	GTPBP4	Q9BZE4	644
MDN1	MRTO4	Q9UKD2	623
MDN1	NOP53	Q9NZM5	586
MDN1	EBNA1BP2	Q99848	571

IntAct

171 interactions, top by confidence:

A	B	Type	Score
TP53	MDM4	psi-mi:“MI:0914”(association)	0.970
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
VSIG1	TTI1	psi-mi:“MI:0914”(association)	0.640
MDN1	PELP1	psi-mi:“MI:0915”(physical association)	0.590
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
	HEATR3	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
VSIG1	TNPO2	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
OPALIN	BTAF1	psi-mi:“MI:0914”(association)	0.530
	C1QBP	psi-mi:“MI:0914”(association)	0.500

BioGRID (263): MDN1 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), MDN1 (Reconstituted Complex), MDN1 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), BRIX1 (Co-fractionation), MDN1 (Proximity Label-MS), WDR12 (Affinity Capture-Western)

ESM2 similar proteins: A0A0R4IC37, A0AUR5, A2RT67, A2RUS2, A5PJM5, A5PKL6, A7E2V1, B1H268, B5DG51, O75694, P48553, P59764, Q0VEJ0, Q14181, Q14997, Q1LX49, Q28DH9, Q28DV7, Q3TLI0, Q4R6Y8, Q5F3K0, Q5JPI3, Q5M8J0, Q5R5S1, Q5RCP7, Q5RL51, Q5XH48, Q5ZJV4, Q6DC53, Q6DDX8, Q6DFF4, Q6DJG6, Q6NX27, Q7ZYP6, Q803A6, Q8C5P5, Q8N1I0, Q8NEC7, Q8R3C0, Q8TAP6

Diamond homologs: O31850, P56540, Q02239, Q2FH29, Q2G2J8, Q2YY09, Q49XL1, Q4L6B6, Q51481, Q51664, Q5HG10, Q5HPD3, Q6G9F2, Q6GGZ9, Q7A0W8, Q7A5N7, Q8CP85, Q8T5T1, Q99U78, Q9NU22, A0A1P8AUY4, O94248, P94474, Q02441, Q12019, Q869L3, B2ITR9, Q3MEF4, Q79FN7, Q8YT32, A0JXL2, A4XAH9, A5CR08, A5GHS5, A8M1K7, A8ZXB8, A9BDA1, A9WUW1, B0RAS4, B1XN45

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MDN1	“up-regulates quantity by stabilization”	PELP1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 207 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.

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	5	19.7×	3e-03
cell surface receptor protein tyrosine kinase signaling pathway	8	7.8×	4e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	14	6.2×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	695
Likely benign	92
Benign	52

Top pathogenic / likely-pathogenic (0)

SpliceAI

14317 predictions. Top by Δscore:

Variant	Effect	Δscore
6:89645158:C:CC	acceptor_gain	1.0000
6:89645165:CCA:C	acceptor_gain	1.0000
6:89645166:C:T	acceptor_gain	1.0000
6:89645166:CATA:C	acceptor_gain	1.0000
6:89645167:A:AC	acceptor_gain	1.0000
6:89645167:A:C	acceptor_gain	1.0000
6:89645169:A:C	acceptor_gain	1.0000
6:89645180:C:CT	acceptor_gain	1.0000
6:89645181:A:T	acceptor_gain	1.0000
6:89646604:C:CC	acceptor_gain	1.0000
6:89646610:C:CT	acceptor_gain	1.0000
6:89646616:C:CT	acceptor_gain	1.0000
6:89646617:A:T	acceptor_gain	1.0000
6:89648026:TCTTA:T	donor_loss	1.0000
6:89648027:CTTA:C	donor_loss	1.0000
6:89648028:TTA:T	donor_loss	1.0000
6:89648029:TACCT:T	donor_loss	1.0000
6:89648030:A:AG	donor_loss	1.0000
6:89648031:C:G	donor_loss	1.0000
6:89648142:CAAAA:C	acceptor_gain	1.0000
6:89648144:AAA:A	acceptor_gain	1.0000
6:89648145:AA:A	acceptor_gain	1.0000
6:89648145:AACT:A	acceptor_loss	1.0000
6:89648146:ACTT:A	acceptor_loss	1.0000
6:89648147:C:CA	acceptor_loss	1.0000
6:89648147:C:CC	acceptor_gain	1.0000
6:89648148:T:C	acceptor_gain	1.0000
6:89648148:T:TC	acceptor_gain	1.0000
6:89648259:CACA:C	donor_gain	1.0000
6:89648326:CAAG:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000014306 (6:89746863 A>G), RS1000033215 (6:89812327 A>G), RS1000058256 (6:89814573 CTT>C,CT), RS1000078267 (6:89768842 G>A,C), RS1000081149 (6:89746550 T>C), RS1000085209 (6:89812193 C>T), RS1000101968 (6:89654581 G>C), RS1000122795 (6:89772001 C>T), RS1000218999 (6:89694986 C>T), RS1000223252 (6:89756808 C>T), RS1000239579 (6:89658528 T>C), RS1000241443 (6:89772268 C>A), RS1000298499 (6:89765880 T>A,C), RS1000299149 (6:89660178 C>A,T), RS1000313522 (6:89704726 G>A)

Disease associations

OMIM: gene MIM:618200 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004033_2	QRS interval (sulfonylurea treatment interaction)	9.000000e-07
GCST005194_75	Coronary artery disease	4.000000e-06
GCST009798_19	Asthma	5.000000e-27

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007922	response to sulfonylurea

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105779 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.32	Kd	47.96	nM	CHEMBL5653589
7.32	ED50	47.96	nM	CHEMBL5653589
5.88	Kd	1315	nM	CHEMBL3699142
5.50	Kd	3148	nM	MOLIBRESIB
5.19	IC50	6390	nM	MOLIBRESIB

PubChem BioAssay actives

4 with measured affinity, of 246 total; 3 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148739: Binding affinity to human MDN1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0480	uM
3-[3-[N-[4-[(dimethylamino)methyl]phenyl]-C-phenylcarbonimidoyl]-2-hydroxy-1H-indol-6-yl]-N-ethylprop-2-ynamide	1425073: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.3150	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179191: Binding affinity against MDN1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	3.1480	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	increases expression	2
Estradiol	increases expression	2
Formaldehyde	decreases expression	2
Tretinoin	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
tamibarotene	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	affects cotreatment, decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
Irinotecan	affects expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991786	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea