METAP1

Summary

METAP1 (methionyl aminopeptidase 1, HGNC:15789) is a protein-coding gene on chromosome 4q23, encoding Methionine aminopeptidase 1 (P53582). Cotranslationally removes the N-terminal methionine from nascent proteins. It is a selective cancer dependency (DepMap: 59.9% of cell lines).

Enables aminopeptidase activity. Involved in protein maturation. Predicted to be located in cytoplasm. Predicted to be active in cytosol.

Source: NCBI Gene 23173 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 49 total — 1 likely-pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 59.9% of screened cell lines
• MANE Select transcript: NM_015143

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15789
Approved symbol	METAP1
Name	methionyl aminopeptidase 1
Location	4q23
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0094, MetAP1A, MAP1A
Ensembl gene	ENSG00000164024
Ensembl biotype	protein_coding
OMIM	610151
Entrez	23173

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000296411, ENST00000503247, ENST00000506238, ENST00000506548, ENST00000507537, ENST00000510107, ENST00000510133, ENST00000510209, ENST00000513097, ENST00000513199, ENST00000514051, ENST00000625963, ENST00000869925, ENST00000869926, ENST00000869927, ENST00000869928, ENST00000924345, ENST00000924346, ENST00000924347, ENST00000924348, ENST00000969299, ENST00000969300

RefSeq mRNA: 1 — MANE Select: NM_015143 NM_015143

CCDS: CCDS47110

Canonical transcript exons

ENST00000296411 — 11 exons

Exon	Start	End
ENSE00001080640	99048733	99048876
ENSE00001080646	99057753	99057818
ENSE00001080647	99045179	99045310
ENSE00001212900	99061154	99062809
ENSE00002071619	98995721	98995867
ENSE00003461298	99043249	99043387
ENSE00003483470	99035400	99035460
ENSE00003593749	99041043	99041126
ENSE00003602529	99039374	99039465
ENSE00003666245	99028867	99028918
ENSE00003685636	99034230	99034342

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 96.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.6054 / max 261.2606, expressed in 1824 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48993	36.2081	1822
48992	8.8248	1775
203292	0.8133	525
48991	0.5134	264
48990	0.1936	80
48997	0.0215	3
48996	0.0210	3
48998	0.0097	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	96.95	gold quality
left testis	UBERON:0004533	96.39	gold quality
epithelium of esophagus	UBERON:0001976	96.38	gold quality
right testis	UBERON:0004534	96.33	gold quality
squamous epithelium	UBERON:0006914	95.94	gold quality
esophagus mucosa	UBERON:0002469	95.37	gold quality
testis	UBERON:0000473	94.99	gold quality
endometrium	UBERON:0001295	94.97	gold quality
descending thoracic aorta	UBERON:0002345	94.85	gold quality
epithelium of nasopharynx	UBERON:0001951	94.82	gold quality
nasopharynx	UBERON:0001728	94.80	gold quality
cervix squamous epithelium	UBERON:0006922	94.75	gold quality
rectum	UBERON:0001052	94.70	gold quality
tongue squamous epithelium	UBERON:0006919	94.62	gold quality
urinary bladder	UBERON:0001255	94.55	gold quality
gingival epithelium	UBERON:0001949	94.54	gold quality
endometrium epithelium	UBERON:0004811	94.50	gold quality
hair follicle	UBERON:0002073	94.48	gold quality
oral cavity	UBERON:0000167	94.31	gold quality
thoracic aorta	UBERON:0001515	94.16	gold quality
ascending aorta	UBERON:0001496	94.09	gold quality
gingiva	UBERON:0001828	93.99	gold quality
left ventricle myocardium	UBERON:0006566	93.91	gold quality
heart right ventricle	UBERON:0002080	93.79	gold quality
thymus	UBERON:0002370	93.59	gold quality
lower esophagus mucosa	UBERON:0035834	93.37	gold quality
esophagus	UBERON:0001043	93.17	gold quality
cortical plate	UBERON:0005343	93.07	gold quality
smooth muscle tissue	UBERON:0001135	93.02	gold quality
corpus epididymis	UBERON:0004359	93.02	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.02
E-MTAB-2983	no	920.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

152 targeting METAP1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-302C-5P	99.97	72.56	3642

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 59.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• Data show that human methionine aminopeptidase 1 (MetAP1) fully rescued the slow growth phenotype associated with deletion of yeast MetAP1, suggesting that the yeast and human proteins may have similar roles in vivo. (PMID:12144506)
• A comparison of the structual differences between Type I and Type II methionine aminopeptidases. (PMID:16274222)
• results suggest that MetAP1 plays an important role in G(2)/M phase of the cell cycle and that it may serve as a promising target for the discovery and development of new anticancer agents (PMID:17114291)
• Human MetAP1 is distinct from other members of the MetAP superfamily in the number of metal ions employed and likely mechanism of catalysis. (PMID:17929833)
• the substrate specificities of Escherichia coli MetAP1, human MetAP1, and human MetAP2 were systematically profiled (PMID:20521764)
• Data indicate that pyridinylpyrimidine-based molecules displayed species specificity behavior against methionine aminopeptidases (MetAPs). (PMID:23767698)
• MetAP1 and MetAP2 have roles in driving cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state (PMID:27542228)
• METAP1 mutation is a novel candidate for autosomal recessive intellectual disability. (PMID:32764695)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	metap1	ENSDARG00000033440
mus_musculus	Metap1	ENSMUSG00000005813
rattus_norvegicus	Metap1	ENSRNOG00000012947
drosophila_melanogaster	CG13630	FBGN0039219
caenorhabditis_elegans		WBGENE00003129

Paralogs (7): XPNPEP1 (ENSG00000108039), METAP2 (ENSG00000111142), XPNPEP2 (ENSG00000122121), PEPD (ENSG00000124299), PA2G4 (ENSG00000170515), METAP1D (ENSG00000172878), XPNPEP3 (ENSG00000196236)

Protein

Protein identifiers

Methionine aminopeptidase 1 — P53582 (reviewed: P53582)

Alternative names: Peptidase M 1

All UniProt accessions (6): D6RF24, P53582, H0Y903, H0Y955, H0Y9L0, H0YAI3

UniProt curated annotations — full annotation on UniProt →

Function. Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Required for normal progression through the cell cycle.

Subunit / interactions. Associates with the 60S ribosomal subunit of the 80S translational complex.

Subcellular location. Cytoplasm.

Cofactor. Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with zinc, cobalt, manganese or divalent iron ions. Has high activity with zinc; zinc cofactor is transferred into the active site region by the ZNG1 zinc chaperone.

Similarity. Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily.

RefSeq proteins (1): NP_055958* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000994	Pept_M24	Domain
IPR001714	Pept_M24_MAP	Family
IPR002467	Pept_M24A_MAP1	Family
IPR031615	Zfn-C6H2	Domain
IPR036005	Creatinase/aminopeptidase-like	Homologous_superfamily

Pfam: PF00557, PF15801

Enzyme classification (BRENDA):

• EC 3.4.11.18 — methionyl aminopeptidase (BRENDA: 45 organisms, 219 substrates, 968 inhibitors, 153 Km, 147 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
MET-GLY-MET-MET	0.058–18.3	20
L-MET-7-AMIDO-4-METHYLCOUMARIN	0.0309–0.5467	16
MET-ALA-SER	0.018–4.54	11
L-MET-GLY-L-MET-L-MET	0.6–3.2	10
L-MET 4-NITROANILIDE	0.154–2.77	9
L-MET-PSI[C(O)S]GLY-L-PHE	0.35–16	8
MET-4-METHYLCOUMARYL-7-AMIDE	0.111–0.168	8
MET-PRO-4-NITROANILIDE	0.06–3.26	7
L-ALANINE-4-METHYLCOUMARIN-7-AMIDE	0.125–0.284	6
L-LEU-7-AMIDO-4-METHYLCOUMARIN	0.0345–0.9795	6
L-METHIONINE 4-NITROANILIDE	0.0002–0.543	4
L-METHIONINE-4-METHYLCOUMARIN-7-AMIDE	0.011–0.17	4
MET-7-AMIDO-4-METHYLCOUMARIN	0.12–6.27	4
L-MET-L-ALA-L-SER	3–15	3
MET-ALA-ALA	1.5–5.2	3

UniProt features (46 total): binding site 17, strand 15, helix 8, turn 2, initiator methionine 1, chain 1, zinc finger region 1, modified residue 1

Structure

Experimental structures (PDB)

41 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2B3H	X-RAY DIFFRACTION	1.1
2GZ5	X-RAY DIFFRACTION	1.1
6LZB	X-RAY DIFFRACTION	1.29
4IKU	X-RAY DIFFRACTION	1.3
6LZC	X-RAY DIFFRACTION	1.35
4FLK	X-RAY DIFFRACTION	1.47
2B3L	X-RAY DIFFRACTION	1.5
2NQ6	X-RAY DIFFRACTION	1.5
4FLL	X-RAY DIFFRACTION	1.5
2B3K	X-RAY DIFFRACTION	1.55
4FLI	X-RAY DIFFRACTION	1.55
4U6J	X-RAY DIFFRACTION	1.56
2NQ7	X-RAY DIFFRACTION	1.6
4IKT	X-RAY DIFFRACTION	1.6
4U69	X-RAY DIFFRACTION	1.6
4U70	X-RAY DIFFRACTION	1.6
5YR5	X-RAY DIFFRACTION	1.6
5YKP	X-RAY DIFFRACTION	1.68
4IKS	X-RAY DIFFRACTION	1.7
4FLJ	X-RAY DIFFRACTION	1.74
5YR6	X-RAY DIFFRACTION	1.75
4IKR	X-RAY DIFFRACTION	1.78
4U6Z	X-RAY DIFFRACTION	1.8
4U71	X-RAY DIFFRACTION	1.8
4U73	X-RAY DIFFRACTION	1.8
5YR4	X-RAY DIFFRACTION	1.82
4U6W	X-RAY DIFFRACTION	1.83
4U76	X-RAY DIFFRACTION	1.87
4U1B	X-RAY DIFFRACTION	1.89
2G6P	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53582-F1	94.44	0.86

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 (17): 52; 203; 220; 231; 231; 294; 301; 327; 358; 358; 9; 14 …

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-2187338	Visual phototransduction
R-HSA-2514856	The phototransduction cascade
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 555 (showing top): VALK_AML_WITH_FLT3_ITD, MORF_MTA1, GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, RNGTGGGC_UNKNOWN, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_COGNITION, GOBP_AXO_DENDRITIC_TRANSPORT, MYOGENIN_Q6, GOBP_BEHAVIOR, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT

GO Biological Process (4): regulation of translation (GO:0006417), proteolysis (GO:0006508), protein maturation (GO:0051604), platelet aggregation (GO:0070527)

GO Molecular Function (9): aminopeptidase activity (GO:0004177), initiator methionyl aminopeptidase activity (GO:0004239), metalloexopeptidase activity (GO:0008235), zinc ion binding (GO:0008270), metalloaminopeptidase activity (GO:0070006), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), cytosolic ribosome (GO:0022626)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
The phototransduction cascade	1
Sensory Perception	1
Visual phototransduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
exopeptidase activity	2
aminopeptidase activity	2
cellular anatomical structure	2
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
gene expression	1
platelet activation	1
homotypic cell-cell adhesion	1
metallopeptidase activity	1
transition metal ion binding	1
metalloexopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
cytosol	1
ribosome	1

Protein interactions and networks

STRING

4228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
METAP1	METAP2	P50579	970
METAP1	EIF2S1	P05198	666
METAP1	MAP1B	P46821	627
METAP1	PDF	Q9HBH1	595
METAP1	DNPEP	Q9ULA0	558
METAP1	DLG2	Q15700	545
METAP1	DLG4	P78352	523
METAP1	MAP1S	Q66K74	514
METAP1	STPG2	Q8N412	508
METAP1	TMEM69	Q5SWH9	476
METAP1	RASSF1	Q9NS23	471
METAP1	ARHGEF11	O15085	462
METAP1	CSNK1D	P48730	453
METAP1	ERAP1	Q9NZ08	452
METAP1	PEPD	P12955	449

IntAct

65 interactions, top by confidence:

A	B	Type	Score
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
BTF3L4	TXLNA	psi-mi:“MI:0914”(association)	0.780
METAP1	ZRANB1	psi-mi:“MI:0915”(physical association)	0.600
ZRANB1	METAP1	psi-mi:“MI:0915”(physical association)	0.600
METAP1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
METAP1	NBR1	psi-mi:“MI:0915”(physical association)	0.560
GLRX3	METAP1	psi-mi:“MI:0915”(physical association)	0.560
METAP1	PLEKHG4	psi-mi:“MI:0915”(physical association)	0.560
METAP1	INCA1	psi-mi:“MI:0915”(physical association)	0.560
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
GH2	METAP1	psi-mi:“MI:0914”(association)	0.530
MRPS12	MTIF2	psi-mi:“MI:0914”(association)	0.530
PLPPR2	METAP2	psi-mi:“MI:0914”(association)	0.530
ZNG1B	METAP1	psi-mi:“MI:0914”(association)	0.530
RSL1D1	METAP1	psi-mi:“MI:0914”(association)	0.530
SYTL4	METAP1	psi-mi:“MI:0915”(physical association)	0.400
METAP1	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
HNRNPU		psi-mi:“MI:0914”(association)	0.350
NCBP3	RSL1D1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
ZNG1B	TCERG1	psi-mi:“MI:0914”(association)	0.350
ZNG1A	AGAP1	psi-mi:“MI:0914”(association)	0.350
NAA40	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
PLPPR2	SEC24D	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (85): METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), METAP1 (Co-fractionation), METAP1 (Co-fractionation), METAP1 (Co-fractionation), METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-RNA)

ESM2 similar proteins: A1CH02, A1CXT5, A2QHX0, A4RDI6, A6QLA4, A6ZKL2, A8QBZ2, B3LNM2, B5VDQ0, B6HTQ4, B6Q1N3, B8LUH2, B8NA06, C4JF09, C5DE35, C7GSF3, C8Z3V4, C9SB49, D1ZEN1, D8PR70, E3QW41, E5R4J3, O08663, O59730, O60085, P38062, P38174, P50579, P53582, Q01662, Q0CL94, Q0UTI9, Q2GSJ7, Q3ZC89, Q4QRK0, Q4VBS4, Q54WU3, Q56Y85, Q5I0A0, Q5RBF3

Diamond homologs: A6QLA4, B6YTG0, O34484, O51132, O59730, O66489, O83814, O84859, P0A078, P0A079, P0A080, P0A1X6, P0A1X7, P0A5J3, P0AE18, P0AE19, P0AE20, P0AE21, P19994, P33111, P41392, P44421, P50614, P53579, P53580, P53581, P53582, P56102, P57324, P69000, P99121, P9WK18, P9WK19, P9WK20, P9WK21, Q01662, Q4QRK0, Q4VBS4, Q54VU7, Q54WU3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	33
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1344737	NM_015143.3(METAP1):c.865C>T (p.Arg289Ter)	Likely pathogenic

SpliceAI

2721 predictions. Top by Δscore:

Variant	Effect	Δscore
15:43517699:GG:G	donor_gain	1.0000
15:43517700:GG:G	donor_gain	1.0000
15:43517701:G:GG	donor_gain	1.0000
15:43519473:GGTC:G	donor_gain	1.0000
15:43520969:CA:C	acceptor_loss	1.0000
15:43521110:GAG:G	donor_gain	1.0000
15:43521111:AGGTA:A	donor_loss	1.0000
15:43521112:GGTA:G	donor_loss	1.0000
15:43521113:GT:G	donor_loss	1.0000
15:43521114:T:A	donor_loss	1.0000
15:43529648:A:AG	acceptor_gain	1.0000
15:43529649:G:GG	acceptor_gain	1.0000
15:43529867:TCAGG:T	donor_loss	1.0000
15:43529868:CAGGT:C	donor_loss	1.0000
15:43529869:AGGTG:A	donor_loss	1.0000
15:43529870:GGTG:G	donor_loss	1.0000
15:43529871:G:GA	donor_loss	1.0000
15:43529872:T:A	donor_loss	1.0000
15:43530065:CTAGG:C	acceptor_loss	1.0000
15:43530066:TAGGT:T	acceptor_loss	1.0000
15:43530067:A:AG	acceptor_gain	1.0000
15:43530067:AGGT:A	acceptor_gain	1.0000
15:43530068:G:GG	acceptor_gain	1.0000
15:43530068:GGT:G	acceptor_gain	1.0000
15:43530068:GGTG:G	acceptor_gain	1.0000
15:43530068:GGTGA:G	acceptor_gain	1.0000
4:98995866:AGGTA:A	donor_loss	1.0000
4:98995867:GGTAG:G	donor_loss	1.0000
4:98995868:G:C	donor_loss	1.0000
4:98995869:T:G	donor_loss	1.0000

AlphaMissense

2524 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:98995812:T:C	L20P	1.000
4:98995817:T:A	C22S	1.000
4:98995817:T:C	C22R	1.000
4:98995818:G:C	C22S	1.000
4:98995826:T:C	C25R	1.000
4:98995827:G:A	C25Y	1.000
4:98995828:C:G	C25W	1.000
4:98995856:T:C	F35L	1.000
4:98995858:C:A	F35L	1.000
4:98995858:C:G	F35L	1.000
4:98995859:T:C	C36R	1.000
4:99028873:T:C	F41L	1.000
4:99028874:T:C	F41S	1.000
4:99028875:T:A	F41L	1.000
4:99028875:T:G	F41L	1.000
4:99028906:C:G	H52D	1.000
4:99043270:T:G	Y180D	1.000
4:99043277:C:T	S182F	1.000
4:99043297:T:C	F189L	1.000
4:99043298:T:C	F189S	1.000
4:99043299:C:A	F189L	1.000
4:99043299:C:G	F189L	1.000
4:99043313:G:A	C194Y	1.000
4:99043314:T:G	C194W	1.000
4:99043336:T:C	C202R	1.000
4:99043337:G:A	C202Y	1.000
4:99043337:G:T	C202F	1.000
4:99043338:C:G	C202W	1.000
4:99043339:C:A	H203N	1.000
4:99043339:C:G	H203D	1.000

dbSNP variants (sampled 300 via entrez): RS1000018402 (4:98994066 C>A,G), RS1000052059 (4:99011901 T>C), RS1000055376 (4:99002308 T>A), RS1000057389 (4:99036012 G>A,T), RS1000074371 (4:99028856 T>C), RS1000160031 (4:99051169 G>A), RS1000160848 (4:99005537 T>A), RS1000188678 (4:99042750 G>A,C), RS1000196823 (4:98993857 G>A), RS1000221887 (4:98999994 G>A,T), RS1000241032 (4:99042995 T>A), RS10002449 (4:99014014 C>T), RS1000339080 (4:99006664 C>A,T), RS1000453816 (4:99007035 A>G), RS1000470478 (4:99049995 T>C)

Disease associations

OMIM: gene MIM:610151 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (2): intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003857_1	Oral cavity and pharyngeal cancer	2.000000e-15
GCST006716_6	Alcohol use disorder (total score)	1.000000e-25
GCST006717_1	Alcohol use disorder (dependence and problematic use scores)	1.000000e-09
GCST006718_3	Alcohol use disorder (consumption score)	4.000000e-17
GCST006921_3	Regular attendance at a pub or social club	4.000000e-25
GCST007328_15	Alcohol consumption (drinks per week)	2.000000e-16
GCST007328_65	Alcohol consumption (drinks per week)	2.000000e-09
GCST011955_1	Alcohol dependence	1.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009458	alcohol use disorder measurement
EFO:0007835	alcohol dependence measurement
EFO:0009592	social interaction measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2474 (SINGLE PROTEIN), CHEMBL3831223 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 75,856 (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
CHEMBL497	CLIOQUINOL	4	12,977
CHEMBL625	THIABENDAZOLE	4	58,476
CHEMBL1170610	BENZOXIQUINE	2	511
CHEMBL225164	CLOXYQUIN	2	3,892

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M24: Methionyl aminopeptidase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 14 [PMID: 23634668]	Inhibition	7.03	pEC50

Binding affinities (BindingDB)

13 measured of 20 human assays (20 total across all organisms); most potent 13 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
bestatin-type inhibitor, 4	IC50	370 nM
tert-butyl N-[2-(1,3-thiazol-2-ylcarbamoyl)pyridin-3-yl]carbamate	IC50	1500 nM
(2S,3S)-3-amino-2-hydroxy-4-[(2-methylpropyl)sulfanyl]-N-[(1S)-1-(naphthalen-1-yl)ethyl]butanamide	IC50	2200 nM
3-(2,2-dimethylpropanamido)-N-(1,3-thiazol-2-yl)pyridine-2-carboxamide	IC50	2900 nM
3-(3-phenylpropanamido)-N-(1,3-thiazol-2-yl)pyridine-2-carboxamide	IC50	3500 nM
3-[(E)-(2-methylpropylidene)amino]-N-(1,3-thiazol-2-yl)pyridine-2-carboxamide	IC50	6400 nM
N’-[(2S,3S)-3-amino-2-hydroxy-4-[(2-methylpropyl)sulfanyl]butanoyl]-3-chlorobenzohydrazide	IC50	8100 nM
(2S,3R)-3-amino-2-hydroxy-N-[(1S)-1-(naphthalen-1-yl)ethyl]-5-(propan-2-ylsulfanyl)pentanamide	IC50	12000 nM
N’-[(2S,3R)-3-amino-5-(ethylsulfanyl)-2-hydroxypentanoyl]-3-chlorobenzohydrazide	IC50	20000 nM
N’-[(2S,3R)-3-amino-2-hydroxy-5-(propan-2-ylsulfanyl)pentanoyl]-3-chlorobenzohydrazide	IC50	57000 nM
ethyl (2S)-2-[(2S,3R)-3-amino-2-hydroxy-5-(methylsulfanyl)pentanamido]propanoate	IC50	63000 nM
ethyl (2S)-2-[(2S,3S)-3-amino-2-hydroxy-4-[(2-methylpropyl)sulfanyl]butanamido]propanoate	IC50	66000 nM
ethyl (2S)-2-[(2S,3R)-3-amino-5-(ethylsulfanyl)-2-hydroxypentanamido]propanoate	IC50	69000 nM

ChEMBL bioactivities

151 potent at pChembl≥5 of 255 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	Kd	0.152	nM	CHEMBL4740594
8.00	Ki	10	nM	CHEMBL271696
7.45	Kd	35.3	nM	CHEMBL4755128
7.44	EC50	36	nM	CHEMBL2392907
7.31	EC50	49	nM	CHEMBL1329554
7.31	EC50	49	nM	CHEMBL2392906
7.20	EC50	63	nM	CHEMBL2392932
7.14	EC50	73	nM	CHEMBL2375615
7.09	EC50	81	nM	CHEMBL2375622
7.07	Kd	85.2	nM	CHEMBL4759563
7.03	EC50	94	nM	CHEMBL2375616
7.03	EC50	94	nM	CHEMBL2375620
7.03	EC50	93	nM	CHEMBL2375609
7.03	EC50	93	nM	CHEMBL2392914
7.00	EC50	100	nM	CHEMBL2375624
7.00	IC50	100	nM	CHEMBL4079583
6.96	EC50	110	nM	CHEMBL2375613
6.96	EC50	110	nM	CHEMBL2375621
6.92	EC50	120	nM	CHEMBL2375612
6.92	EC50	120	nM	CHEMBL2375610
6.85	EC50	140	nM	CHEMBL2392910
6.80	EC50	160	nM	CHEMBL2392933
6.80	EC50	160	nM	CHEMBL2392915
6.75	EC50	180	nM	CHEMBL2375618
6.72	EC50	190	nM	CHEMBL472879
6.70	EC50	200	nM	CHEMBL2392934
6.70	EC50	200	nM	CHEMBL2392921
6.66	EC50	220	nM	CHEMBL2392918
6.60	EC50	250	nM	CHEMBL2375608
6.58	EC50	260	nM	CHEMBL2392920
6.58	EC50	260	nM	CHEMBL2392919
6.57	EC50	270	nM	CHEMBL2392905
6.55	EC50	280	nM	CHEMBL2375628
6.52	EC50	300	nM	CHEMBL2392909
6.50	EC50	320	nM	DIPYRIDYL
6.48	EC50	330	nM	CHEMBL2392928
6.48	EC50	330	nM	CHEMBL2392908
6.46	EC50	350	nM	CHEMBL327579
6.44	EC50	360	nM	CHEMBL327579
6.44	IC50	360	nM	CHEMBL2392772
6.44	Kd	361	nM	CHEMBL4743733
6.43	IC50	370	nM	CHEMBL352943
6.42	EC50	380	nM	CHEMBL2392929
6.41	EC50	390	nM	CHEMBL2375614
6.41	EC50	390	nM	CHEMBL2375607
6.40	IC50	400	nM	CHEMBL327579
6.39	EC50	410	nM	CHEMBL45721
6.38	EC50	420	nM	CHEMBL2392924
6.37	EC50	430	nM	CHEMBL2375627
6.30	EC50	500	nM	CHEMBL2392931

PubChem BioAssay actives

161 with measured affinity, of 636 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
3-(3-fluorophenyl)-2-(8-hydroxyquinolin-2-yl)-1,3-thiazolidin-4-one	1717147: Binding affinity to human MetAP1 expressed in Escherichia coli BL21 (DE3) by surface plasmon resonance analysis	kd	0.0002	uM
5-[(E)-3-[4-(dimethylamino)phenyl]prop-2-enylidene]-1,3-diazinane-2,4,6-trione	322264: Inhibition of human methionine aminopeptidase 1	ki	0.0100	uM
3-[2-(8-hydroxyquinolin-2-yl)-4-oxo-1,3-thiazolidin-3-yl]benzonitrile	1717147: Binding affinity to human MetAP1 expressed in Escherichia coli BL21 (DE3) by surface plasmon resonance analysis	kd	0.0353	uM
N-[(1R)-2-[[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]amino]-1-phenylethyl]-4-piperazin-1-ylbutanamide	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.0360	uM
4-(2-pyridin-2-ylquinazolin-4-yl)morpholine	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.0490	uM
N-[(1R)-2-[[5-chloro-2-(5-fluoro-2-pyridinyl)-6-methylpyrimidin-4-yl]amino]-1-phenylethyl]-4-piperazin-1-ylbutanamide	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.0490	uM
5-chloro-2-(5-chloro-2-pyridinyl)-N-(2,4-diphenylbutyl)-6-methylpyrimidin-4-amine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.0630	uM
1-[4-[4-(2-pyridin-2-ylquinolin-4-yl)piperazin-1-yl]phenyl]ethanol	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.0730	uM
4-[4-(2-pyridin-2-ylquinolin-4-yl)piperazin-1-yl]benzaldehyde	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.0810	uM
2-(8-hydroxyquinolin-2-yl)-3-(4-methylphenyl)-1,3-thiazolidin-4-one	1717147: Binding affinity to human MetAP1 expressed in Escherichia coli BL21 (DE3) by surface plasmon resonance analysis	kd	0.0852	uM
N-[(1R)-2-[[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]amino]-1-phenylethyl]-3-phenylpropanamide	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.0930	uM
N-[(2S)-1-oxo-3-phenyl-1-[4-(2-pyridin-2-ylquinolin-4-yl)piperazin-1-yl]propan-2-yl]acetamide	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.0930	uM
4-[4-(2-pyridin-2-ylquinolin-4-yl)piperazin-1-yl]phenol	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.0940	uM
ethyl 4-[4-(2-pyridin-2-ylquinolin-4-yl)piperazin-1-yl]benzoate	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.0940	uM
4-[4-(4-methoxyphenyl)piperazin-1-yl]-2-pyridin-2-ylquinazoline	1484178: Inhibition of human MetAP1	ic50	0.1000	uM
4-[4-(4-methoxyphenyl)piperazin-1-yl]-2-pyridin-2-ylquinoline	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.1000	uM
4-[4-(4-nitrophenyl)piperazin-1-yl]-2-pyridin-2-ylquinoline	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.1100	uM
4-piperidin-1-yl-2-pyridin-2-ylquinazoline	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.1100	uM
N-[5-[2-oxo-2-[4-(2-pyridin-2-ylquinolin-4-yl)piperazin-1-yl]ethyl]-1,3-thiazol-2-yl]acetamide	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.1200	uM
N-[2-(2H-isoindol-1-yl)ethyl]-2-pyridin-2-ylquinazolin-4-amine	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.1200	uM
N-[(1R)-2-[[5-chloro-2-[5-(dimethylamino)-2-pyridinyl]-6-methylpyrimidin-4-yl]amino]-1-phenylethyl]-4-piperazin-1-ylbutanamide	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.1400	uM
N-[(1R)-2-[[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]amino]-1-phenylethyl]-4-phenylbutanamide	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.1600	uM
5-chloro-2-(5-chloro-2-pyridinyl)-N-(2,5-diphenylpentyl)-6-methylpyrimidin-4-amine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.1600	uM
ethyl 2-[4-[4-(2-pyridin-2-ylquinolin-4-yl)piperazin-1-yl]phenoxy]acetate	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.1800	uM
5-chloro-6-methyl-N-(2-phenylethyl)-2-pyridin-2-ylpyrimidin-4-amine	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.1900	uM
(1R)-N’-[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]-1-phenyl-N-(4-phenylbutyl)ethane-1,2-diamine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.2000	uM
5-chloro-2-(5-chloro-2-pyridinyl)-N-(2,6-diphenylhexyl)-6-methylpyrimidin-4-amine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.2000	uM
(1R)-N-benzyl-N’-[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]-1-phenylethane-1,2-diamine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.2200	uM
4-[4-(4-methylphenyl)sulfonylpiperazin-1-yl]-2-pyridin-2-ylquinoline	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.2500	uM
(1R)-N’-[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]-1-phenyl-N-(2-phenylethyl)ethane-1,2-diamine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.2600	uM
(1R)-N’-[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]-1-phenyl-N-(3-phenylpropyl)ethane-1,2-diamine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.2600	uM
N-[(1R)-2-[[5-chloro-2-(5-methoxy-2-pyridinyl)-6-methylpyrimidin-4-yl]amino]-1-phenylethyl]-4-piperazin-1-ylbutanamide	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.2700	uM
N’-(5-chloro-6-methyl-2-pyridin-2-ylpyrimidin-4-yl)-N-[5-(trifluoromethyl)-2-pyridinyl]ethane-1,2-diamine	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.2800	uM
N-[(1R)-2-[[5-chloro-6-methyl-2-(5-nitro-2-pyridinyl)pyrimidin-4-yl]amino]-1-phenylethyl]-4-piperazin-1-ylbutanamide	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.3000	uM
2-pyridin-2-ylpyridine	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.3200	uM
N-[(1R)-2-[[2-(5-bromo-2-pyridinyl)-5-chloro-6-methylpyrimidin-4-yl]amino]-1-phenylethyl]-4-piperazin-1-ylbutanamide	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.3300	uM
(1R)-N’-[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]-N-[4-(furan-2-yl)butyl]-1-phenylethane-1,2-diamine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.3300	uM
tert-butyl N-[2-(1,3-thiazol-2-ylcarbamoyl)-3-pyridinyl]carbamate	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.3500	uM
5-chloro-N-[1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]piperidin-4-yl]-6-methyl-2-pyridin-2-ylpyrimidin-4-amine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ic50	0.3600	uM
3-(4-chlorophenyl)-2-(8-hydroxyquinolin-2-yl)-1,3-thiazolidin-4-one	1717147: Binding affinity to human MetAP1 expressed in Escherichia coli BL21 (DE3) by surface plasmon resonance analysis	kd	0.3610	uM
(2S,3R)-3-amino-5-ethylsulfanyl-2-hydroxy-N-[(1S)-1-naphthalen-1-ylethyl]pentanamide	107918: Inhibitory activity against human methionine aminopeptidase-1	ic50	0.3700	uM
(1R)-N’-[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]-1-phenyl-N-(4-thiophen-2-ylbutyl)ethane-1,2-diamine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.3800	uM
4-piperidin-1-yl-2-pyridin-2-ylquinoline	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.3900	uM
4-[4-(3,4-dichlorophenyl)piperazin-1-yl]-2-pyridin-2-ylquinoline	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.3900	uM
4-(2-pyridin-2-ylquinolin-4-yl)morpholine	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.4100	uM
4-[4-[[(1R)-2-[[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]amino]-1-phenylethyl]amino]butyl]phenol	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.4200	uM
(1S)-N’-[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]-1-phenyl-N-(4-phenylbutyl)ethane-1,2-diamine	745691: Inhibition of human methionine aminopeptidase 1 in presence of Co2+	ec50	0.4300	uM
(1R)-N’-[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]-1-phenyl-N-(4-pyrrol-1-ylbutyl)ethane-1,2-diamine	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.5000	uM
4-[4-[[(1R)-2-[[5-chloro-2-(5-chloro-2-pyridinyl)-6-methylpyrimidin-4-yl]amino]-1-phenylethyl]amino]butyl]benzonitrile	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.5200	uM
N-[(1R)-2-[[5-chloro-2-(4-methoxy-2-pyridinyl)-6-methylpyrimidin-4-yl]amino]-1-phenylethyl]-4-piperazin-1-ylbutanamide	751992: Inhibition of human recombinant full-length cytosolic METAP1 expressed in Escherichia coli BL21(DE3) using Met-Pro-p-nitroanilide as substrate after 20 mins by spectrophotometric analysis in presence of Bacillus coagulans GST-tagged proline iminopeptidase	ec50	0.5300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, decreases reaction, decreases expression	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	decreases expression, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
cobaltous chloride	decreases expression	1
fumagillin	decreases activity, affects cotreatment, decreases metabolic processing	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
3,4,5-trihydroxy-2–methoxy-8,8-dimethyl-N-(hexahydro-2-oxo-6-(cyclohexylcarbonyl)oxy-2H-azepin-3-yl)non-6-enamide	decreases activity, affects cotreatment, decreases metabolic processing	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Air Pollutants, Occupational	affects expression	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Dimethyl Sulfoxide	decreases expression	1
Doxorubicin	decreases expression	1
Gasoline	increases abundance, affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Phthalic Acids	increases methylation	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Ribonucleotides	affects binding, decreases reaction	1
Rotenone	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Cyclosporine	increases methylation	1

ChEMBL screening assays

79 unique, capped per target: 75 binding, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1027136	Binding	Inhibition of methionine aminopeptidase 1	A selective account of effective paradigms and significant outcomes in the discovery of inspirational marine natural products. — J Nat Prod
CHEMBL4417040	ADMET	Inhibition of N-terminal MetAP1 (unknown origin)	Identification of Methionine Aminopeptidase-2 (MetAP-2) Inhibitor M8891: A Clinical Compound for the Treatment of Cancer. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays