MXI1

Summary

MXI1 (MAX interactor 1, dimerization protein, HGNC:7534) is a protein-coding gene on chromosome 10q25.2, encoding Max-interacting protein 1 (P50539). Transcriptional repressor.

Expression of the c-myc gene, which produces an oncogenic transcription factor, is tightly regulated in normal cells but is frequently deregulated in human cancers. The protein encoded by this gene is a transcriptional repressor thought to negatively regulate MYC function, and is therefore a potential tumor suppressor. This protein inhibits the transcriptional activity of MYC by competing for MAX, another basic helix-loop-helix protein that binds to MYC and is required for its function. Defects in this gene are frequently found in patients with prostate tumors. Three alternatively spliced transcripts encoding different isoforms have been described. Additional alternatively spliced transcripts may exist but the products of these transcripts have not been verified experimentally.

Source: NCBI Gene 4601 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 71 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 3
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_130439

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7534
Approved symbol	MXI1
Name	MAX interactor 1, dimerization protein
Location	10q25.2
Locus type	gene with protein product
Status	Approved
Aliases	MXD2, MAD2, MXI, bHLHc11
Ensembl gene	ENSG00000119950
Ensembl biotype	protein_coding
OMIM	600020
Entrez	4601

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 26 protein_coding, 11 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000239007, ENST00000332674, ENST00000361248, ENST00000369612, ENST00000393134, ENST00000442296, ENST00000453116, ENST00000460667, ENST00000484030, ENST00000485566, ENST00000650644, ENST00000650696, ENST00000650752, ENST00000650810, ENST00000650843, ENST00000650900, ENST00000650952, ENST00000651004, ENST00000651109, ENST00000651112, ENST00000651167, ENST00000651225, ENST00000651318, ENST00000651467, ENST00000651495, ENST00000651516, ENST00000651557, ENST00000651613, ENST00000651811, ENST00000651848, ENST00000651866, ENST00000652028, ENST00000652243, ENST00000652323, ENST00000652463, ENST00000652506, ENST00000652604, ENST00000652649

RefSeq mRNA: 3 — MANE Select: NM_130439 NM_001008541, NM_005962, NM_130439

CCDS: CCDS31284, CCDS7563, CCDS7564

Canonical transcript exons

ENST00000332674 — 6 exons

Exon	Start	End
ENSE00001349097	110284824	110287365
ENSE00001435090	110207605	110208082
ENSE00003522489	110244828	110244857
ENSE00003551958	110279914	110280085
ENSE00003600992	110279180	110279294
ENSE00003624798	110228189	110228321

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.2060 / max 1915.6790, expressed in 1808 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106953	24.3247	1665
106956	14.3066	1678
106959	1.3446	388
106957	0.3836	148
106951	0.3435	167
106954	0.2152	103
106952	0.1569	56
106958	0.1309	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cranial nerve II	UBERON:0000941	99.12	gold quality
calcaneal tendon	UBERON:0003701	99.09	gold quality
corpus callosum	UBERON:0002336	98.79	gold quality
inferior vagus X ganglion	UBERON:0005363	98.66	gold quality
trabecular bone tissue	UBERON:0002483	98.62	gold quality
parotid gland	UBERON:0001831	98.61	gold quality
middle frontal gyrus	UBERON:0002702	98.54	gold quality
subthalamic nucleus	UBERON:0001906	98.51	gold quality
lateral globus pallidus	UBERON:0002476	98.40	gold quality
postcentral gyrus	UBERON:0002581	98.36	gold quality
paraflocculus	UBERON:0005351	98.25	gold quality
medulla oblongata	UBERON:0001896	98.22	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.22	gold quality
parietal lobe	UBERON:0001872	98.21	gold quality
ventral tegmental area	UBERON:0002691	98.07	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.03	gold quality
corpus epididymis	UBERON:0004359	97.97	gold quality
popliteal artery	UBERON:0002250	97.96	gold quality
superior vestibular nucleus	UBERON:0007227	97.95	gold quality
tibial artery	UBERON:0007610	97.95	gold quality
caput epididymis	UBERON:0004358	97.93	gold quality
globus pallidus	UBERON:0001875	97.90	gold quality
inferior olivary complex	UBERON:0002127	97.76	gold quality
cauda epididymis	UBERON:0004360	97.76	gold quality
medial globus pallidus	UBERON:0002477	97.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.70	gold quality
spinal cord	UBERON:0002240	97.69	gold quality
lower esophagus	UBERON:0013473	97.69	gold quality
aorta	UBERON:0000947	97.58	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	28.85
E-MTAB-9221	yes	21.94
E-HCAD-9	yes	6.67
E-MTAB-9067	no	3.91
E-MTAB-9467	no	1.44
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
CCNB1	Repression
CXCL8	Activation
GLMN
GNAS
IFT20
MAX
MXI1
MYC	Repression
MYCN	Unknown
ODC1

JASPAR motifs

Motif	Name	Family
MA1108.1	MXI1	bHLH-ZIP
MA1108.2	MXI1	bHLH-ZIP
MA1108.3	MXI1	bHLH-ZIP

JASPAR matrix evidence (PMIDs): PMID:8425219

Upstream regulators (CollecTRI, top): E2F1, HIF1A, MXI1, MYC, MYCN, TFAP2A

miRNA regulators (miRDB)

169 targeting MXI1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3617-3P	99.98	67.86	918
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-433-3P	99.98	69.37	1203
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4799-5P	99.82	70.60	2663

Literature-anchored findings (GeneRIF, showing 23)

• Mxi1 can act as a tumour suppressor in human glioblastomas through a molecular mechanism involving the transcriptional down-regulation of cyclin B1 gene expression. (PMID:11875718)
• These findings support MXI1 as a putative tumor suppressor gene involved in conventional melanoma progression. (PMID:14559981)
• Mxi1-SRalpha is an isoform with enhanced transcriptional repression potential (PMID:15467743)
• Data show that PTEN and MXI1 were two candidate tumor suppressor genes on 10q23 and 10q24-q25 and may be potentially involved in the initiation and progression of prostate carcinoma. (PMID:15476185)
• Mxi-D may play an important role in the c-Myc family protein network acting as a dominant negative isoform of Mxi-F stimulated by c-Myc (PMID:15809730)
• p300 can acetylate DNA-bound Myc:Max complexes and that acetylated Myc:Max heterodimers efficiently interact with Miz-1 (PMID:16126174)
• MXI1 mutation appears to play a role in the pathogenesis of a small subset of cases, and suggests an alternative mechanism to MYC amplification for disruption of the MYC/MAD/MAX network in medulloblastoma. (PMID:17102621)
• These results provide evidence of direct regulation of Mxi1 by FOXO3a and imply an additional mechanism through which the PI3-kinase/Akt/FOXO pathway can modulate Myc function. (PMID:17452451)
• Mad1, Mxi1 and Rox genes were expressed and displayed mutations in haematological malignancies. (PMID:17577784)
• Mxi1 gains functional complexity by encoding isoforms with shared and distinct activities (PMID:17697116)
• Missense mutations in Mad1, Mxi1 and Rox were found in acute leukemia patients. (PMID:18457265)
• Mxi1 is an important downstream target of HIF that contributes to pVHL-deficient renal cancer tumorigenesis (PMID:19018165)
• MAX interactor-1 (MXI1) gene is directly regulated by HIF-1alpha protein in neuroblastoma and breast cancer cells. (PMID:19254710)
• These findings reveal, for the first time, the novel functions of cooperation of miR243p and miR27a3p from two clusters in promoting cell proliferation through MXI1. (PMID:23254855)
• MicroRNA-155 promotes glioma cell proliferation via the regulation of MXI1. (PMID:24376632)
• MXI1-0 appears to be a downstream target of MYCN-dependent signaling pathways and may contribute to N-Myc-dependent cell growth and proliferation. (PMID:24403858)
• MYC-HEG and MXI1-LEG levels are associated with poor prognosis in patients with breast cancer, suggesting that they may be useful molecular markers in breast cancer prognosis prediction. (PMID:24685915)
• Reactive oxygen species mediates hypoxia-induced VEGF by upregulation of Mxi1-0. (PMID:28065785)
• results suggest that Mxi1-0 regulates the growth of HUVECs via the IL-8 and ERK1/2 pathways, which apparently reciprocally activate each other (PMID:28575053)
• a phosphorylation mutant form of Mxi1 (Mxi1-S160A), which cannot be degraded by S6K1 and beta-Trcp, is much more stable and efficient in suppressing the transcriptional activity of Myc and radioresistance in lung cancer cells. (PMID:29507620)
• HIF-1alpha-induced FOXO3a promotes apoptosis of hypoxic endothelial cells by directly inducing Mxi1- 0, which leads to the activation of caspase-8 apoptotic pathway. (PMID:30118760)
• UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance. (PMID:32901121)
• Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis. (PMID:35501353)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mxi1	ENSDARG00000040884
mus_musculus	Mxi1	ENSMUSG00000025025
rattus_norvegicus	Mxi1	ENSRNOG00000034078
caenorhabditis_elegans		WBGENE00003163

Paralogs (4): MXD1 (ENSG00000059728), MNT (ENSG00000070444), MXD4 (ENSG00000123933), MXD3 (ENSG00000213347)

Protein

Protein identifiers

Max-interacting protein 1 — P50539 (reviewed: P50539)

Alternative names: Class C basic helix-loop-helix protein 11

All UniProt accessions (12): P50539, A0A0S2Z3X5, A0A0S2Z3Y0, A0A0S2Z429, A0A494BZS3, A0A494C0I8, A0A494C0W2, A0A494C1C1, A0A494C1P8, B1ANN8, F6U3F6, F6WCI9

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor. MXI1 binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5’-CAC[GA]TG-3’. MXI1 thus antagonizes MYC transcriptional activity by competing for MAX.

Subunit / interactions. Interacts with SMC3. Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX. Interacts with RNF17.

Subcellular location. Nucleus.

Tissue specificity. High levels found in the brain, heart and lung while lower levels are seen in the liver, kidney and skeletal muscle.

Disease relevance. Prostate cancer (PC) [MIM:176807] A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
P50539-1	1	yes
P50539-2	2
P50539-3	3
P50539-4	4

RefSeq proteins (3): NP_001008541, NP_005953, NP_569157* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00010

UniProt features (13 total): compositionally biased region 4, splice variant 3, region of interest 2, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50539-F1	73.25	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 423 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, AHRARNT_01, RNGTGGGC_UNKNOWN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, KOBAYASHI_EGFR_SIGNALING_24HR_UP, GRUETZMANN_PANCREATIC_CANCER_DN, PAX4_01, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, CMYB_01, MODULE_418, MENSE_HYPOXIA_UP, GCAAGGA_MIR502, IVANOVA_HEMATOPOIESIS_MATURE_CELL, FOXO4_01, DARWICHE_PAPILLOMA_PROGRESSION_RISK

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), blastocyst formation (GO:0001825), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), protein dimerization activity (GO:0046983), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), RNA polymerase II transcription regulator complex (GO:0090575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
nuclear lumen	2
negative regulation of DNA-templated transcription	1
blastocyst development	1
anatomical structure formation involved in morphogenesis	1
regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
protein binding	1
transcription cis-regulatory region binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1330 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MXI1	MAX	P25912	979
MXI1	MYC	P01106	890
MXI1	SIN3B	O75182	745
MXI1	SIN3A	Q96ST3	741
MXI1	NCOR1	O75376	694
MXI1	LZTS2	Q9BRK4	662
MXI1	HIF1A	Q16665	660
MXI1	E2F6	O75461	657
MXI1	INVS	Q9Y283	642
MXI1	SIX5	Q8N196	622
MXI1	RAD21	O60216	621
MXI1	MXD1	Q05195	613
MXI1	SMC3	Q9UQE7	610
MXI1	FOXO3	O43524	593
MXI1	E2F4	Q16254	576

IntAct

27 interactions, top by confidence:

A	B	Type	Score
MAX	MXI1	psi-mi:“MI:0915”(physical association)	0.900
MXI1	MAX	psi-mi:“MI:0915”(physical association)	0.900
MAX	E2F6	psi-mi:“MI:0914”(association)	0.710
MXI1	ENTPD5	psi-mi:“MI:0915”(physical association)	0.560
CALCOCO2	MXI1	psi-mi:“MI:0915”(physical association)	0.560
DKFZp547I014	MXI1	psi-mi:“MI:0915”(physical association)	0.560
MXI1	MAX	psi-mi:“MI:0915”(physical association)	0.560
ENTPD5	MXI1	psi-mi:“MI:0915”(physical association)	0.560
MAX	MXI1	psi-mi:“MI:0915”(physical association)	0.560
MXI1	SMARCB1	psi-mi:“MI:0915”(physical association)	0.370
Max	PABPN1	psi-mi:“MI:0914”(association)	0.350
MAX	SMARCA5	psi-mi:“MI:0914”(association)	0.350
BTRC	ACOT7	psi-mi:“MI:0914”(association)	0.350
MAX	AGRN	psi-mi:“MI:0914”(association)	0.350
MXD3	SAP30	psi-mi:“MI:0914”(association)	0.350

BioGRID (85): MXI1 (Two-hybrid), MXI1 (Two-hybrid), CALCOCO2 (Two-hybrid), RPL23AP32 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), MXI1 (Two-hybrid), MXI1 (Affinity Capture-Western), MXI1 (Affinity Capture-MS), MXI1 (Affinity Capture-MS)

ESM2 similar proteins: A1L2X1, D4A7E1, E1BD44, F1QW76, F7EMX9, G5ECU7, G5EF76, O09015, O35284, O57598, O96642, P13096, P13097, P13098, P13903, P46505, P50539, P50540, P50541, P97831, P97876, Q00P32, Q01068, Q01069, Q01070, Q01071, Q04788, Q05195, Q07291, Q09771, Q09926, Q0VFI9, Q0VH34, Q10574, Q16520, Q18711, Q21361, Q23579, Q62282, Q8AW52

Diamond homologs: G5EG44, O09015, P50538, P50539, P50540, P50541, Q05195, Q0VFI9, Q0VH33, Q0VH34, Q14582, Q28DB3, Q60948, Q62912, Q7SX95, Q80US8, Q9BW11, O08789, P28574, P52162, P52164, P61244, P61245, Q07016, Q0VH32, Q99583, P49709, P52160, Q7ZVS9, Q90342

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MAX	“up-regulates activity”	MXI1	binding
MXI1	“down-regulates quantity by repression”	CCNB1	“transcriptional regulation”
RPS6KB1	“down-regulates activity”	MXI1	phosphorylation
SMC3	“down-regulates activity”	MXI1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	46
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
9534	NM_130439.3(MXI1):c.623del (p.Lys208fs)	Pathogenic
9535	NM_130439.3(MXI1):c.552+2T>C	Pathogenic
9536	NM_130439.3(MXI1):c.656A>C (p.Glu219Ala)	Pathogenic
9537	NM_130439.3(MXI1):c.362C>T (p.Ala121Val)	Pathogenic
2445390	NM_130439.3(MXI1):c.314C>T (p.Pro105Leu)	Likely pathogenic

SpliceAI

1892 predictions. Top by Δscore:

Variant	Effect	Δscore
10:110208078:CAAAA:C	donor_gain	1.0000
10:110208079:AAAA:A	donor_gain	1.0000
10:110208080:AAA:A	donor_gain	1.0000
10:110208081:AA:A	donor_gain	1.0000
10:110208081:AAG:A	donor_loss	1.0000
10:110208082:AGT:A	donor_loss	1.0000
10:110208083:G:GG	donor_gain	1.0000
10:110208083:GTA:G	donor_loss	1.0000
10:110228184:TTCA:T	acceptor_loss	1.0000
10:110228184:TTCAG:T	acceptor_gain	1.0000
10:110228185:TCAG:T	acceptor_gain	1.0000
10:110228186:CAG:C	acceptor_gain	1.0000
10:110228186:CAGA:C	acceptor_loss	1.0000
10:110228187:A:AC	acceptor_loss	1.0000
10:110228187:A:AG	acceptor_gain	1.0000
10:110228187:AGA:A	acceptor_gain	1.0000
10:110228187:AGAGT:A	acceptor_gain	1.0000
10:110228188:G:GA	acceptor_gain	1.0000
10:110228188:GA:G	acceptor_gain	1.0000
10:110228188:GAG:G	acceptor_gain	1.0000
10:110228188:GAGT:G	acceptor_gain	1.0000
10:110228188:GAGTG:G	acceptor_gain	1.0000
10:110244826:A:AG	acceptor_gain	1.0000
10:110244827:G:GG	acceptor_gain	1.0000
10:110263903:G:GT	donor_gain	1.0000
10:110279178:A:AG	acceptor_gain	1.0000
10:110279178:AGAC:A	acceptor_gain	1.0000
10:110279179:G:GG	acceptor_gain	1.0000
10:110279179:GAC:G	acceptor_gain	1.0000
10:110279179:GACG:G	acceptor_gain	1.0000

AlphaMissense

1928 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:110279212:T:C	L90S	0.999
10:110244849:A:C	E76D	0.998
10:110244849:A:T	E76D	0.998
10:110279191:T:C	L83P	0.998
10:110279266:T:C	L108S	0.998
10:110279269:T:A	L109H	0.998
10:110279269:T:C	L109P	0.998
10:110279277:G:C	A112P	0.998
10:110279278:C:A	A112D	0.998
10:110244852:G:C	K77N	0.997
10:110244852:G:T	K77N	0.997
10:110244857:G:C	R79P	0.997
10:110279193:C:A	R84S	0.997
10:110279254:C:T	T104I	0.997
10:110244848:A:T	E76V	0.996
10:110279203:T:C	L87S	0.996
10:110279260:T:C	L106P	0.996
10:110279918:T:C	L119P	0.996
10:110244847:G:A	E76K	0.995
10:110244850:A:C	K77Q	0.995
10:110244850:A:G	K77E	0.995
10:110244851:A:T	K77M	0.995
10:110279191:T:A	L83Q	0.995
10:110279215:A:T	K91I	0.995
10:110279216:A:C	K91N	0.995
10:110279216:A:T	K91N	0.995
10:110244835:C:G	H72D	0.994
10:110244845:T:C	L75P	0.994
10:110244851:A:C	K77T	0.994
10:110279194:G:C	R84P	0.994

dbSNP variants (sampled 300 via entrez): RS1000004772 (10:110232551 G>A,C), RS1000026769 (10:110208624 T>C), RS1000059367 (10:110208341 C>G), RS1000078444 (10:110239745 A>T), RS1000092516 (10:110256150 T>C), RS1000161154 (10:110214414 AC>A), RS1000186230 (10:110273327 A>G), RS1000190155 (10:110259291 A>G), RS1000241438 (10:110229135 C>T), RS1000259586 (10:110266359 C>T), RS1000275176 (10:110277226 A>G), RS1000289121 (10:110215703 G>A), RS1000326174 (10:110277511 A>C,G), RS1000373596 (10:110221986 C>T), RS1000375513 (10:110270063 G>A)

Disease associations

OMIM: gene MIM:600020 | disease phenotypes: MIM:167000

GenCC curated gene-disease

Mondo (3): ovarian cancer (MONDO:0008170), prostate cancer (MONDO:0008315), neurofibrosarcoma (MONDO:0002675)

Orphanet (2): Rare ovarian cancer (Orphanet:213500), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0012125	Prostate cancer

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000268_4	Normalized brain volume	8.000000e-06
GCST005973_10	White blood cell count	7.000000e-10
GCST005974_8	Neutrophil count	4.000000e-08
GCST005991_17	Platelet count	4.000000e-08
GCST006627_69	Diastolic blood pressure	2.000000e-09
GCST008362_120	Birth weight	4.000000e-08
GCST010002_224	Refractive error	2.000000e-14
GCST010304_50	Cutaneous malignant melanoma	3.000000e-06
GCST90002398_185	Neutrophil count	3.000000e-11
GCST90002407_315	White blood cell count	3.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0004309	platelet count
EFO:0006336	diastolic blood pressure
EFO:0004344	birth weight

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018319	Neurofibrosarcoma	C04.557.450.565.590.350.590; C04.557.450.795.350.590; C04.557.580.600.580.795; C10.551.775.500.750.750; C10.668.829.725.500.600.600
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	4
bisphenol A	affects cotreatment, increases methylation, increases expression	3
Cisplatin	decreases expression, affects expression, affects cotreatment, increases expression	3
trichostatin A	affects expression, increases expression	2
nickel chloride	increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases expression	2
Oxygen	increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
TAK-243	increases sumoylation	1
chloroacetaldehyde	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
geraniol	increases expression	1
methylselenic acid	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
zinc chromate	increases expression, increases abundance	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
cupric oxide	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
JP8 aviation fuel	decreases expression	1
oxamflatin	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4G7	SEES3-1V human MXI1, clone1	Embryonic stem cell	Male
CVCL_A4G8	SEES3-1V human MXI1, clone2	Embryonic stem cell	Male
CVCL_A4G9	SEES3-1V human MXI1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	PHASE3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	PHASE3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	PHASE3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	PHASE3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer