MLX

Summary

MLX (MAX dimerization protein MLX, HGNC:11645) is a protein-coding gene on chromosome 17q21.2, encoding Max-like protein X (Q9UH92). Transcription regulator. It is a selective cancer dependency (DepMap: 19.1% of cell lines).

The product of this gene belongs to the family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors. These factors form heterodimers with Mad proteins and play a role in proliferation, determination and differentiation. This gene product may act to diversify Mad family function by its restricted association with a subset of the Mad family of transcriptional repressors, namely, Mad1 and Mad4. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.

Source: NCBI Gene 6945 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 56 total — 2 pathogenic
• Phenotypes (HPO): 54
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 19.1% of screened cell lines
• MANE Select transcript: NM_198204

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11645
Approved symbol	MLX
Name	MAX dimerization protein MLX
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	MAD7, MXD7, bHLHd13
Ensembl gene	ENSG00000108788
Ensembl biotype	protein_coding
OMIM	602976
Entrez	6945

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 7 retained_intron

ENST00000246912, ENST00000346833, ENST00000435881, ENST00000585403, ENST00000586393, ENST00000588320, ENST00000590050, ENST00000590084, ENST00000591024, ENST00000591195, ENST00000592717, ENST00000873680, ENST00000913726, ENST00000913727, ENST00000913728, ENST00000913729, ENST00000913730, ENST00000913731, ENST00000948562

RefSeq mRNA: 3 — MANE Select: NM_198204 NM_170607, NM_198204, NM_198205

CCDS: CCDS11430, CCDS42341, CCDS45687

Canonical transcript exons

ENST00000435881 — 8 exons

Exon	Start	End
ENSE00000865357	42568470	42568559
ENSE00001222947	42567100	42567166
ENSE00003588467	42567619	42567655
ENSE00003602779	42569507	42569606
ENSE00003608840	42569204	42569303
ENSE00003634454	42569982	42570183
ENSE00003678369	42568837	42568943
ENSE00003904900	42571547	42573203

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.2551 / max 136.6561, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160964	28.7742	1819
208199	1.1015	825
160963	0.7761	534
160965	0.4462	220
160966	0.1571	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.01	gold quality
secondary oocyte	CL:0000655	97.00	gold quality
parotid gland	UBERON:0001831	96.15	gold quality
duodenum	UBERON:0002114	95.65	gold quality
mucosa of transverse colon	UBERON:0004991	95.65	gold quality
apex of heart	UBERON:0002098	95.54	gold quality
colonic mucosa	UBERON:0000317	95.53	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.31	gold quality
jejunal mucosa	UBERON:0000399	95.23	gold quality
ileal mucosa	UBERON:0000331	95.18	gold quality
rectum	UBERON:0001052	95.16	gold quality
heart left ventricle	UBERON:0002084	95.02	gold quality
cardiac ventricle	UBERON:0002082	95.01	gold quality
gastrocnemius	UBERON:0001388	94.80	gold quality
granulocyte	CL:0000094	94.76	gold quality
muscle of leg	UBERON:0001383	94.65	gold quality
heart right ventricle	UBERON:0002080	94.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.61	gold quality
left ventricle myocardium	UBERON:0006566	94.57	gold quality
monocyte	CL:0000576	94.54	gold quality
diaphragm	UBERON:0001103	94.54	gold quality
muscle organ	UBERON:0001630	94.45	gold quality
mononuclear cell	CL:0000842	94.43	gold quality
leukocyte	CL:0000738	94.42	gold quality
transverse colon	UBERON:0001157	94.31	gold quality
myocardium	UBERON:0002349	94.28	gold quality
gingival epithelium	UBERON:0001949	94.26	gold quality
gluteal muscle	UBERON:0002000	94.26	gold quality
body of stomach	UBERON:0001161	94.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.32
E-HCAD-10	yes	7.27

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
ARNT
COL11A1
ODC1	Unknown
PKLR	Unknown
SLU7
TXNIP	Unknown

JASPAR motifs

Motif	Name	Family
MA0663.1	MLX	bHLH-ZIP

JASPAR matrix evidence (PMIDs): PMID:14742444

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

93 targeting MLX, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-377-5P	99.70	65.28	712

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 19.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• Data show that for both MondoA and Mlx, the C-terminal domain CRM-1 has cytoplasmic localization activity that is required by the protein monomers to accumulate in the cytoplasm. (PMID:12446771)
• Mlx is an obligatory partner of ChREBP in regulating lipogenic enzyme genes in liver. (PMID:15664996)
• Endogenous MondoA and Mlx associate with mitochondria in primary skeletal muscle. (PMID:16782875)
• These studies suggest a key role for MondoA:Mlx complexes in the adaptive transcriptional response to changes in extracellular glucose concentration and peripheral glucose uptake. (PMID:18458340)
• MYC is part of a network of bHLHLZ proteins centered on the MYC heterodimeric partner MAX and its counterpart, the MAX-like protein MLX. (PMID:24857747)
• Knockdown of MondoA, or its dimerization partner Mlx, blocks Myc-induced reprogramming of multiple metabolic pathways, resulting in apoptosis (PMID:25640402)
• MLX-Q139R mutation plays a crucial role in the pathogenesis of Takayasu arteritis through promoting inflammasome formation. (PMID:30354298)
• The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells. (PMID:31919096)
• MLX plays a key role in lipid and glucose metabolism in humans: Evidence from in vitro and in vivo studies. (PMID:37088121)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mlx	ENSDARG00000037891
mus_musculus	Mlx	ENSMUSG00000017801
rattus_norvegicus	Mlx	ENSRNOG00000019983
drosophila_melanogaster	bigmax	FBGN0039509

Paralogs (3): MLXIPL (ENSG00000009950), TFAP4 (ENSG00000090447), MLXIP (ENSG00000175727)

Protein

Protein identifiers

Max-like protein X — Q9UH92 (reviewed: Q9UH92)

Alternative names: Class D basic helix-loop-helix protein 13, Max-like bHLHZip protein, Protein BigMax, Transcription factor-like protein 4

All UniProt accessions (2): Q9UH92, K7EID0

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MAD1, MAD4, MNT, WBSCR14 and MLXIP which recognizes the core sequence 5’-CACGTG-3’. The TCFL4-MAD1, TCFL4-MAD4, TCFL4-WBSCR14 complexes are transcriptional repressors. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAD1, MAD4, MNT, WBSCR14 and MLXIP. Can also bind DNA as a homodimer.

Subcellular location. Cytoplasm Cytoplasm Nucleus.

Tissue specificity. Expressed in all tissues tested, including spleen, thymus, prostate, ovary, intestine, colon, peripheral blood leukocyte, heart, liver, skeletal muscle and kidney. Lower levels of expression in testis, brain, placenta and lung.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UH92-1	Gamma	yes
Q9UH92-2	Alpha
Q9UH92-3	Beta

RefSeq proteins (3): NP_733752, NP_937847, NP_937848 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR052207	Max-like/E-box_TFs	Family

Pfam: PF00010

UniProt features (20 total): modified residue 6, compositionally biased region 4, region of interest 3, splice variant 2, sequence conflict 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UH92-F1	73.71	0.45

Functional residue map

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

Post-translational modifications (6): 45, 48, 74, 77, 98, 7

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163765	ChREBP activates metabolic gene expression
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism

MSigDB gene sets: 272 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE45365_NK_CELL_VS_BCELL_UP, TATTATA_MIR374, TGACCTY_ERR1_Q2, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, TGCTGAY_UNKNOWN, GENTILE_UV_HIGH_DOSE_DN, GENTILE_UV_RESPONSE_CLUSTER_D5, TATCTGG_MIR488, PEART_HDAC_PROLIFERATION_CLUSTER_UP, GOBP_CARBOHYDRATE_HOMEOSTASIS, TCCAGAG_MIR518C, SENESE_HDAC1_TARGETS_UP, AP2GAMMA_01, OSMAN_BLADDER_CANCER_DN

GO Biological Process (5): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (12): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515), protein dimerization activity (GO:0046983)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear membrane (GO:0031965)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Integration of energy metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
DNA-templated transcription	2
transcription cis-regulatory region binding	2
protein dimerization activity	2
negative regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	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
transcription regulator activity	1
identical protein binding	1
DNA-binding transcription factor binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
binding	1
protein binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nucleus	1
nuclear envelope	1
organelle membrane	1

Protein interactions and networks

STRING

756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MLX	MXD4	Q14582	927
MLX	MNT	Q99583	872
MLX	NTRK1	P04629	780
MLX	NIF3L1	Q9GZT8	765
MLX	HSD17B1	P14061	725
MLX	PKLR	P11973	652
MLX	ZNF92	Q03936	644
MLX	MLXIPL	Q9NP71	612
MLX	LIPN	Q5VXI9	572
MLX	XPO1	O14980	549
MLX	SIN3A	Q96ST3	501
MLX	SP6	Q3SY56	430
MLX	FIGLA	Q6QHK4	426
MLX	MXI1	P50539	421
MLX	MLXIP	Q9HAP2	421

IntAct

37 interactions, top by confidence:

A	B	Type	Score
GABARAPL2	MLX	psi-mi:“MI:0915”(physical association)	0.740
MLX	GABARAPL2	psi-mi:“MI:0915”(physical association)	0.740
MLX	TLE5	psi-mi:“MI:0915”(physical association)	0.670
TLE5	MLX	psi-mi:“MI:0915”(physical association)	0.670
RBM39	MLX	psi-mi:“MI:0915”(physical association)	0.560
ZBTB32	MLX	psi-mi:“MI:0915”(physical association)	0.560
MLX	ZBTB32	psi-mi:“MI:0915”(physical association)	0.560
HBZ	MLX	psi-mi:“MI:0915”(physical association)	0.560
MLX	HBZ	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CCL5	MLX	psi-mi:“MI:0915”(physical association)	0.370
	MLX	psi-mi:“MI:0915”(physical association)	0.370
TNFSF14	MLX	psi-mi:“MI:0915”(physical association)	0.370
MLX	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	MLX	psi-mi:“MI:0915”(physical association)	0.370
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAG	BRAF	psi-mi:“MI:0914”(association)	0.350

BioGRID (100): MLX (Two-hybrid), RBM39 (Two-hybrid), GABARAPL2 (Two-hybrid), ZBTB32 (Two-hybrid), MLX (Reconstituted Complex), MLX (Affinity Capture-RNA), GABARAPL2 (Two-hybrid), MLX (Proximity Label-MS), MLXIP (Affinity Capture-MS), MLXIPL (Affinity Capture-MS), CSPG5 (Affinity Capture-MS), CSNK2A2 (Affinity Capture-MS), BACH1 (Affinity Capture-MS), CSNK2A1 (Affinity Capture-MS), SNX1 (Affinity Capture-MS)

ESM2 similar proteins: A4IGK3, B7ZAP0, O08609, O54941, O55047, O60519, P18847, P26801, P28574, P29596, P37285, P52161, P52162, P52164, P60762, P61244, P61245, P97875, Q07016, Q07866, Q08CW1, Q08DJ0, Q0VCP9, Q0VD32, Q13330, Q28772, Q2KII1, Q32KT0, Q32M00, Q3T0B9, Q56A18, Q5BJU6, Q5R581, Q5ZIL4, Q60765, Q62599, Q642H2, Q6PH81, Q78E65, Q7TMY4

Diamond homologs: O08609, Q2VPU4, Q8VIP2, Q99MZ3, Q9HAP2, Q9NP71, Q9UH92, P41846, Q9TZ70, A0A286LEZ9, O02818, P0DPB0, P22415, P28574, P49379, P52161, P52162, P52164, P61244, P61245, P91664, Q07016, Q07956, Q07957, Q10186, Q15853, Q5A1E3, Q61069, Q63665, Q64705, Q6XBT4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
G2/M DNA damage checkpoint	5	31.6×	1e-05
Signaling by Rho GTPases	6	10.8×	1e-04
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	6	10.6×	1e-04
Viral Infection Pathways	5	8.1×	2e-03
Infectious disease	5	6.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	33
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
30741	NM_016556.4(PSMC3IP):c.600_602del	Pathogenic
812136	NM_016556.4(PSMC3IP):c.614del (p.Glu205fs)	Pathogenic

SpliceAI

1366 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42567611:T:TA	acceptor_gain	1.0000
17:42567653:CCGGT:C	donor_loss	1.0000
17:42567654:CGGTG:C	donor_loss	1.0000
17:42567655:GGT:G	donor_loss	1.0000
17:42567656:G:C	donor_loss	1.0000
17:42567657:T:A	donor_loss	1.0000
17:42568823:A:AG	acceptor_gain	1.0000
17:42568824:T:G	acceptor_gain	1.0000
17:42568828:T:TA	acceptor_gain	1.0000
17:42568914:GC:G	donor_gain	1.0000
17:42568928:G:GT	donor_gain	1.0000
17:42568932:G:T	donor_gain	1.0000
17:42568939:TCAAG:T	donor_loss	1.0000
17:42568940:CAAGG:C	donor_loss	1.0000
17:42568941:AAGG:A	donor_loss	1.0000
17:42568952:G:GT	donor_gain	1.0000
17:42568953:G:T	donor_gain	1.0000
17:42569276:C:G	donor_gain	1.0000
17:42569302:GA:G	donor_gain	1.0000
17:42569304:G:GG	donor_gain	1.0000
17:42569316:A:T	donor_gain	1.0000
17:42569505:A:AG	acceptor_gain	1.0000
17:42569506:G:GA	acceptor_gain	1.0000
17:42569506:GCC:G	acceptor_gain	1.0000
17:42569506:GCCAT:G	acceptor_gain	1.0000
17:42569578:G:GT	donor_gain	1.0000
17:42569602:A:T	donor_gain	1.0000
17:42569603:AAGT:A	donor_gain	1.0000
17:42569605:GT:G	donor_gain	1.0000
17:42569607:G:GG	donor_gain	1.0000

AlphaMissense

1633 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42568905:C:G	H134D	1.000
17:42568907:C:A	H134Q	1.000
17:42568907:C:G	H134Q	1.000
17:42568921:A:C	Q139P	1.000
17:42568927:G:C	R141T	1.000
17:42568927:G:T	R141M	1.000
17:42568928:G:C	R141S	1.000
17:42568928:G:T	R141S	1.000
17:42568930:G:C	R142T	1.000
17:42568930:G:T	R142M	1.000
17:42568931:G:C	R142S	1.000
17:42568931:G:T	R142S	1.000
17:42568935:G:C	A144P	1.000
17:42568939:T:A	I145N	1.000
17:42568939:T:C	I145T	1.000
17:42568939:T:G	I145S	1.000
17:42569220:T:A	L152H	1.000
17:42569220:T:C	L152P	1.000
17:42569232:T:A	V156D	1.000
17:42569292:T:A	V176D	1.000
17:42569295:T:A	L177Q	1.000
17:42569295:T:C	L177P	1.000
17:42568905:C:A	H134N	0.999
17:42568914:G:C	A137P	0.999
17:42568919:G:C	E138D	0.999
17:42568919:G:T	E138D	0.999
17:42568926:A:G	R141G	0.999
17:42568929:A:G	R142G	0.999
17:42569208:G:A	G148D	0.999
17:42569210:T:C	Y149H	0.999

dbSNP variants (sampled 300 via entrez): RS1000695609 (17:42566078 A>G), RS1000709121 (17:42571644 T>C,G), RS1000841194 (17:42573037 G>A), RS1000890947 (17:42573578 T>C,G), RS1001058400 (17:42567559 A>C), RS1001551543 (17:42567861 G>A), RS1001728994 (17:42570725 G>A), RS1002268298 (17:42568348 G>A), RS1002294647 (17:42568196 C>A,T), RS1002813873 (17:42572217 T>C), RS1002869698 (17:42565646 C>T), RS1002960805 (17:42571054 G>A), RS1003302885 (17:42569669 C>A,G,T), RS1003550138 (17:42566284 T>C), RS1003940032 (17:42569245 G>A)

Disease associations

OMIM: gene MIM:602976 | disease phenotypes: MIM:614324

GenCC curated gene-disease

Mondo (1): ovarian dysgenesis 3 (MONDO:0013689)

Orphanet (1): 46,XX gonadal dysgenesis (Orphanet:243)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000488	Retinopathy
HP:0000505	Visual impairment
HP:0000822	Hypertension
HP:0001250	Seizure
HP:0001297	Stroke
HP:0001324	Muscle weakness
HP:0001369	Arthritis
HP:0001635	Congestive heart failure
HP:0001644	Dilated cardiomyopathy
HP:0001646	Abnormal aortic valve morphology
HP:0001654	Abnormal heart valve morphology
HP:0001658	Myocardial infarction
HP:0001659	Aortic regurgitation
HP:0001824	Weight loss
HP:0001903	Anemia
HP:0001920	Renal artery stenosis
HP:0001945	Fever
HP:0002039	Anorexia
HP:0002076	Migraine
HP:0002092	Pulmonary arterial hypertension
HP:0002094	Dyspnea
HP:0002105	Hemoptysis
HP:0002167	Abnormal speech pattern
HP:0002315	Headache
HP:0002321	Vertigo
HP:0002326	Transient ischemic attack
HP:0002617	Vascular dilatation
HP:0002633	Vasculitis
HP:0002637	Cerebral ischemia
HP:0002829	Arthralgia

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000879_46	Crohn’s disease	3.000000e-08
GCST007515_19	Type 2 diabetes	2.000000e-08
GCST007847_53	Type 2 diabetes	4.000000e-08
GCST007847_69	Type 2 diabetes	2.000000e-06
GCST009379_183	Type 2 diabetes	2.000000e-12
GCST010766_1	Type 2 diabetes (time to event)	3.000000e-08
GCST90020025_1440	Waist-to-hip ratio adjusted for BMI	6.000000e-09
GCST90020027_412	Waist-hip index	9.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004918	age at diagnosis
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2062357 (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: 281 (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
CHEMBL2063869	GDC-0152	1	281

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

ChEMBL bioactivities

8 potent at pChembl≥5 of 8 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.85	Ki	14	nM	GDC-0152
7.80	Ki	16	nM	CHEMBL2063868
7.52	Ki	30	nM	CHEMBL2063862
7.52	Ki	30	nM	CHEMBL2063863
7.16	Ki	70	nM	CHEMBL2063866
7.10	Ki	80	nM	CHEMBL2063865
7.05	Ki	90	nM	CHEMBL2063867
6.34	Ki	460	nM	CHEMBL2063864

PubChem BioAssay actives

8 with measured affinity, of 8 total; 8 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
(2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-(4-phenylthiadiazol-5-yl)pyrrolidine-2-carboxamide	676467: Displacement of 5-FAM-conjugated AVP-diPhe-FAM from MLXBIR3SG after 30 mins by fluorescence polarization-based competition assay	ki	0.0140	uM
(2S)-1-[(2S)-2-[[(2S)-2-(methylamino)propanoyl]amino]-2-phenylacetyl]-N-(4-phenylthiadiazol-5-yl)pyrrolidine-2-carboxamide	676467: Displacement of 5-FAM-conjugated AVP-diPhe-FAM from MLXBIR3SG after 30 mins by fluorescence polarization-based competition assay	ki	0.0160	uM
(2S)-N-(2,2-diphenylethyl)-1-[(2S)-3-methyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]pyrrolidine-2-carboxamide	676467: Displacement of 5-FAM-conjugated AVP-diPhe-FAM from MLXBIR3SG after 30 mins by fluorescence polarization-based competition assay	ki	0.0300	uM
(4R)-3-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-(2,2-diphenylethyl)-1,3-thiazolidine-4-carboxamide	676467: Displacement of 5-FAM-conjugated AVP-diPhe-FAM from MLXBIR3SG after 30 mins by fluorescence polarization-based competition assay	ki	0.0300	uM
(2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-(2,2-diphenylethyl)pyrrolidine-2-carboxamide	676467: Displacement of 5-FAM-conjugated AVP-diPhe-FAM from MLXBIR3SG after 30 mins by fluorescence polarization-based competition assay	ki	0.0700	uM
(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2,3-dihydroxypropyl]amino]propanoyl]amino]-3-methylbutanoyl]-N-(2,2-diphenylethyl)pyrrolidine-2-carboxamide	676467: Displacement of 5-FAM-conjugated AVP-diPhe-FAM from MLXBIR3SG after 30 mins by fluorescence polarization-based competition assay	ki	0.0800	uM
(2S)-N-[(4-chlorophenyl)methyl]-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]pyrrolidine-2-carboxamide	676467: Displacement of 5-FAM-conjugated AVP-diPhe-FAM from MLXBIR3SG after 30 mins by fluorescence polarization-based competition assay	ki	0.0900	uM
(2S)-1-[(2S)-2-[[(2S)-2-(cyclopropylmethylamino)propanoyl]amino]-3-methylbutanoyl]-N-(2,2-diphenylethyl)pyrrolidine-2-carboxamide	676467: Displacement of 5-FAM-conjugated AVP-diPhe-FAM from MLXBIR3SG after 30 mins by fluorescence polarization-based competition assay	ki	0.4600	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases stability	3
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Vanadates	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2066545	Binding	Displacement of 5-FAM-conjugated AVP-diPhe-FAM from MLXBIR3SG after 30 mins by fluorescence polarization-based competition assay	Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). — J Med Chem

Clinical trials (associated diseases)

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