METAP2

Summary

METAP2 (methionyl aminopeptidase 2, HGNC:16672) is a protein-coding gene on chromosome 12q22, encoding Methionine aminopeptidase 2 (P50579). Cotranslationally removes the N-terminal methionine from nascent proteins. It is a selective cancer dependency (DepMap: 68.1% of cell lines).

The protein encoded by this gene is a member of the methionyl aminopeptidase family. The encoded protein functions both by protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation and by removing the amino-terminal methionine residue from nascent proteins. Increased expression of this gene is associated with various forms of cancer, and the anti-cancer drugs fumagillin and ovalicin inhibit the protein by irreversibly binding to its active site. Inhibitors of this gene have also been shown to be effective for the treatment of obesity. A pseudogene of this gene is located on chromosome 2. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10988 — RefSeq curated summary.

At a glance

• GWAS associations: 26 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 325 total — 1 pathogenic (top 10% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈4% of expected missense variation)
• GTEx eGene: eQTL in 16 tissues, sQTL in 3 (q < 0.05)
• Drug target: yes — 2 curated mechanism-of-action drugs; 10 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Cancer dependency (DepMap): dependent in 68.1% of screened cell lines
• Constraint (gnomAD): pLI 0.05 (LoF-tolerant), LOEUF 0.75 (unconstrained)
• MANE Select transcript: NM_006838
• Interaction hub: 2,607 STRING partners (top 4% of genes corpus-wide)
• Notable: 325 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16672
Approved symbol	METAP2
Name	methionyl aminopeptidase 2
Location	12q22
Locus type	gene with protein product
Status	Approved
Aliases	MNPEP, p67, MAP2
Ensembl gene	ENSG00000111142
Ensembl biotype	protein_coding
OMIM	601870
Entrez	10988

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 25 protein_coding, 7 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000323666

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 4: 2, TSL 5: 3

ENST00000323666, ENST00000261220, ENST00000535095, ENST00000546478, ENST00000546753, ENST00000549136, ENST00000549502, ENST00000549808, ENST00000550777, ENST00000551840, ENST00000553151, ENST00000878866, ENST00000878867, ENST00000934960, ENST00000934961, ENST00000934962, ENST00000934963, ENST00000934964, ENST00000934965, ENST00000947084, ENST00000947085, ENST00000947086, ENST00000947087, ENST00000987393, ENST00000987395, ENST00001037891, ENST00001063196, ENST00001063199, ENST00001063200, ENST00001101134, ENST00001107846, ENST00001115039, ENST00001126452, ENST00001137373

RefSeq mRNA: 4 — MANE Select: NM_006838 NM_001317182, NM_001317183, NM_001330246, NM_006838

CCDS: CCDS81723, CCDS81724, CCDS81725, CCDS9052

Canonical transcript exons

ENST00000323666 — 11 exons

Exon	Start	End
ENSE00000753404	95483215	95483280
ENSE00000753405	95485879	95485981
ENSE00000753406	95494056	95494217
ENSE00000753407	95494957	95495138
ENSE00000753408	95496004	95496098
ENSE00000922696	95504065	95504161
ENSE00000922697	95511895	95511998
ENSE00001295819	95513652	95515839
ENSE00002357869	95474152	95474330
ENSE00003575452	95476071	95476178
ENSE00003635249	95512801	95512916

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 118.8213 / max 2644.2238, expressed in 1827 samples.

Highest expression (Bgee): sural nerve, seminal vesicle, calcaneal tendon, tendon, tendon of biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

METAP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	8.5e-14	+0.44	12:95509356:A:G
Artery Tibial	eqtl	4.0e-07	-0.20	12:95477567:G:A
Adrenal Gland	eqtl	1.3e-05	-0.25	12:95523067:A:G
Testis	sqtl	4.8e-05	-0.52	12:95520422:G:A
Testis	eqtl	6.3e-05	+0.20	12:95507107:G:A
Skin Sun Exposed Lower leg	eqtl	3.7e-04	+0.16	12:95531158:T:C
Artery Aorta	eqtl	7.2e-04	-0.19	12:95447891:G:C
Heart Atrial Appendage	eqtl	1.2e-03	-0.18	12:95496950:G:T
Breast Mammary Tissue	sqtl	3.1e-03	-0.46	12:95450792:C:A
Nerve Tibial	eqtl	4.4e-03	+0.11	12:95519210:T:TAC
Thyroid	eqtl	4.7e-03	-0.10	12:95415908:G:A
Esophagus Muscularis	eqtl	8.4e-03	+0.09	12:95342359:C:T
Cells EBV-transformed lymphocytes	eqtl	1.2e-02	+0.09	12:95447483:C:T
Cells EBV-transformed lymphocytes	sqtl	1.7e-02	+0.37	12:94594790:C:T
Brain Cerebellum	eqtl	2.2e-02	+0.23	12:95503034:G:A
Muscle Skeletal	eqtl	2.4e-02	-0.21	12:95432420:C:T
Brain Putamen basal ganglia	eqtl	3.0e-02	-0.19	12:95164703:T:A
Cells Cultured fibroblasts	eqtl	4.3e-02	+0.05	12:95340970:A:G
Brain Nucleus accumbens basal ganglia	eqtl	4.3e-02	+0.17	12:95410150:A:G

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
127441	104.0800	1827
127440	10.3354	1749
127439	4.4059	1531

Top tissues by expression

showing 100 of 301 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	99.10	gold quality
seminal vesicle	UBERON:0000998	98.42	gold quality
calcaneal tendon	UBERON:0003701	98.42	gold quality
tendon	UBERON:0000043	97.74	gold quality
tendon of biceps brachii	UBERON:0008188	97.71	gold quality
trabecular bone tissue	UBERON:0002483	97.64	gold quality
oral cavity	UBERON:0000167	97.25	gold quality
secondary oocyte	CL:0000655	97.10	gold quality
ganglionic eminence	UBERON:0004023	97.10	gold quality
embryo	UBERON:0000922	97.02	gold quality
endometrium	UBERON:0001295	97.02	gold quality
colonic epithelium	UBERON:0000397	97.00	gold quality
adrenal tissue	UBERON:0018303	96.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.97	gold quality
cauda epididymis	UBERON:0004360	96.92	gold quality
ventricular zone	UBERON:0003053	96.83	gold quality
medial globus pallidus	UBERON:0002477	96.80	gold quality
biceps brachii	UBERON:0001507	96.77	gold quality
descending thoracic aorta	UBERON:0002345	96.74	gold quality
parotid gland	UBERON:0001831	96.69	gold quality
mammalian vulva	UBERON:0000997	96.68	gold quality
tonsil	UBERON:0002372	96.64	gold quality
corpus epididymis	UBERON:0004359	96.57	gold quality
globus pallidus	UBERON:0001875	96.47	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.44	gold quality
cortical plate	UBERON:0005343	96.33	gold quality
stromal cell of endometrium	CL:0002255	96.24	gold quality
superficial temporal artery	UBERON:0001614	96.22	gold quality
cartilage tissue	UBERON:0002418	96.17	gold quality
gastrocnemius	UBERON:0001388	96.09	gold quality
right adrenal gland cortex	UBERON:0035827	96.07	gold quality
muscle of leg	UBERON:0001383	96.06	gold quality
right adrenal gland	UBERON:0001233	96.00	gold quality
islet of Langerhans	UBERON:0000006	95.99	gold quality
body of pancreas	UBERON:0001150	95.93	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.91	gold quality
smooth muscle tissue	UBERON:0001135	95.88	gold quality
left adrenal gland	UBERON:0001234	95.88	gold quality
rectum	UBERON:0001052	95.80	gold quality
gall bladder	UBERON:0002110	95.80	gold quality
skin of abdomen	UBERON:0001416	95.79	gold quality
blood vessel layer	UBERON:0004797	95.79	gold quality
adrenal gland	UBERON:0002369	95.77	gold quality
right coronary artery	UBERON:0001625	95.76	gold quality
monocyte	CL:0000576	95.75	gold quality
mucosa of stomach	UBERON:0001199	95.74	gold quality
lower lobe of lung	UBERON:0008949	95.74	gold quality
vermiform appendix	UBERON:0001154	95.73	gold quality
lateral globus pallidus	UBERON:0002476	95.66	gold quality
left adrenal gland cortex	UBERON:0035825	95.59	gold quality
penis	UBERON:0000989	95.58	gold quality
uterus	UBERON:0000995	95.57	gold quality
adrenal cortex	UBERON:0001235	95.57	gold quality
mononuclear cell	CL:0000842	95.54	gold quality
caecum	UBERON:0001153	95.51	gold quality
caput epididymis	UBERON:0004358	95.48	gold quality
urinary bladder	UBERON:0001255	95.47	gold quality
popliteal artery	UBERON:0002250	95.45	gold quality
tibial artery	UBERON:0007610	95.45	gold quality
aorta	UBERON:0000947	95.43	gold quality
thoracic aorta	UBERON:0001515	95.42	gold quality
left coronary artery	UBERON:0001626	95.42	gold quality
artery	UBERON:0001637	95.42	gold quality
zone of skin	UBERON:0000014	95.41	gold quality
lymph node	UBERON:0000029	95.41	gold quality
subthalamic nucleus	UBERON:0001906	95.40	gold quality
left ovary	UBERON:0002119	95.39	gold quality
gluteal muscle	UBERON:0002000	95.38	gold quality
triceps brachii	UBERON:0001509	95.37	gold quality
skin of hip	UBERON:0001554	95.37	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.37	gold quality
pancreas	UBERON:0001264	95.36	gold quality
leukocyte	CL:0000738	95.34	gold quality
heart right ventricle	UBERON:0002080	95.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.32	gold quality
ascending aorta	UBERON:0001496	95.31	gold quality
mammary duct	UBERON:0001765	95.25	gold quality
skin of leg	UBERON:0001511	95.23	gold quality
corpus callosum	UBERON:0002336	95.23	gold quality
body of uterus	UBERON:0009853	95.23	gold quality
bone element	UBERON:0001474	95.22	gold quality
endocervix	UBERON:0000458	95.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.19	gold quality
lower esophagus	UBERON:0013473	95.18	gold quality
coronary artery	UBERON:0001621	95.15	gold quality
epithelium of nasopharynx	UBERON:0001951	95.13	gold quality
sigmoid colon	UBERON:0001159	95.12	gold quality
nasopharynx	UBERON:0001728	95.11	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.11	gold quality
colonic mucosa	UBERON:0000317	95.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.08	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.08	gold quality
ovary	UBERON:0000992	95.07	gold quality
muscle organ	UBERON:0001630	95.07	gold quality
upper leg skin	UBERON:0004262	95.07	gold quality
skeletal muscle organ	UBERON:0014892	95.07	gold quality
pigmented layer of retina	UBERON:0001782	95.04	gold quality
retina	UBERON:0000966	95.02	gold quality
bronchial epithelial cell	CL:0002328	95.00	gold quality
left uterine tube	UBERON:0001303	94.97	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	142.38
E-CURD-122	yes	19.98
E-GEOD-111727	no	1208.04
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 156 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Hippocampal formation	tissue	831.8
Cerebral cortex	tissue	819.5	high
Motor cortex	tissue	819.5
Postcentral gyrus	tissue	797.9
Prefrontal cortex	tissue	786.2
Temporal cortex	tissue	782.3
Insular cortex	tissue	769.1
Amygdala	tissue	754.2
Occipital cortex	tissue	739.9
Somatosensory cortex	tissue	727.9
Retrosplenial cortex	tissue	725.5
Entorhinal cortex	tissue	722.8
Retrosplenial and cingulate cortex	tissue	697.5
Frontal cortex	tissue	658.5
Hypothalamus	tissue	567.1
Olfactory bulb	tissue	524.1
Thalamus	tissue	471.0
Locus coeruleus	tissue	459.8
Putamen	tissue	452.6
Ventral forebrain	tissue	451.4
Septum	tissue	443.8
Midbrain	tissue	439.4
Caudate putamen	tissue	437.0
Pons	tissue	435.6
Hippocampus	tissue	430.2	high
Basal ganglia	tissue	419.8	high
Periaqueductal gray	tissue	394.2
Retina	tissue	379.4
Nucleus accumbens	tissue	378.6
Superior colliculi	tissue	377.4
Medulla oblongata	tissue	293.0
Cerebellum	tissue	287.3	high
Substantia nigra	tissue	281.8
Spinal cord	tissue	200.2
Corpus callosum	tissue	122.9
Tonsil	tissue	117.0	high
Skeletal muscle	tissue	111.9	low
Bone marrow	tissue	96.4	high
Seminal vesicle	tissue	95.1	high
Liver	tissue	78.9	medium
Tongue	tissue	73.5
Lymph node	tissue	72.8	high
Caudate putamen	tissue	69.1
Ovary	tissue	65.6	low
Thymus	tissue	64.4
Postcentral gyrus	tissue	63.7
Heart muscle	tissue	61.6	low
Frontal cortex	tissue	59.6
Urinary bladder	tissue	58.1	medium
Testis	tissue	57.8	high
Skin 1	tissue	55.0	medium
Adrenal gland	tissue	54.2	medium
Nucleus accumbens	tissue	53.7
Choroid plexus	tissue	52.1
Hippocampus	tissue	52.1	medium
Kidney	tissue	51.8	high
Breast	tissue	51.5	medium
Smooth muscle	tissue	51.3	low
Esophagus	tissue	51.1	medium
Endometrium 1	tissue	50.7	medium

Brain sub-regions (HPA Brain Atlas): detected in 381; highest nTPM — Subiculum (831.8), Arcuate nucleus (749.2), Ventral hippocampus (661.0), Dorsal hippocampus (632.8), Perirhinal gyrus (569.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, PLAGL2

miRNA regulators (miRDB)

Targeting METAP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 105 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
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-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-1323	99.83	69.89	2471

Functional genomics

gnomAD constraint: pLI 0.0492, LOEUF 0.754, missense Z 2.68 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000323666 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈4% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
12:95,474,180–95,494,083	177 / 180.3	0.98	no
12:95,494,084–95,511,932	106 / 221.9	0.48	no
12:95,511,933–95,511,985	1 / 22.7	0.04	yes (p 5.2e-06)
12:95,511,986–95,513,901	82 / 156.2	0.52	no
DepMap (CRISPR cell-line fitness): dependent in 68.1% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): OV-90 (-1.336), Hey-A8 (-1.288), BHT-101 (-1.269), SIMA (-1.265), HUP-T4 (-1.253), NCI-H2887 (-1.211), UACC-893 (-1.196), PSN1 (-1.19), RERF-LC-AI (-1.18), HCC-78 (-1.159), SU.86.86 (-1.136), HCC-56 (-1.133), Caki-1 (-1.12), VM-CUB1 (-1.112), LS513 (-1.108).

Literature-anchored findings (GeneRIF, showing 24)

• the functional role of S100A4 in regulating endothelial cell growth and tumor metastasis involves interaction with the N-terminal half of Methionine Aminopeptidase 2. (PMID:11994292)
• High expression in germinal center B cells and their neoplastic counterparts. (PMID:12118091)
• Divalent metal cofactors are physiologically relevant for activity of this enzyme. (PMID:12718546)
• MetAP protein has a role in colorectal adenocarcinoma progression (PMID:15102683)
• Expressed in colon cancer cells (PMID:15336565)
• MetAP-1 and MetAP-2 have essential functions in the control of mammalian cell proliferation (PMID:15962312)
• A comparison of the structual differences between Type I and Type II methionine aminopeptidases. (PMID:16274222)
• Data suggest that methionine aminopeptidase 2 plays a role in the proliferation of fibroblasts and myofibroblasts in fibrotic lung diseases and may serve as a novel pharmacologic target in idiopathic pulmonary fibrosis. (PMID:17446530)
• MetAP2 plays an important role in tumor cell growth and may contribute to tumorigenesis (PMID:18264137)
• Discovery, identification, and characterization of candidate pharmacodynamic markers of METAP2 inhibition are reported. (PMID:18828628)
• Data indicate that MetAP2 expression and pp60c-src phosphorylation were decreased in NC2213 treated cells. (PMID:19703310)
• the substrate specificities of Escherichia coli MetAP1, human MetAP1, and human MetAP2 were systematically profiled (PMID:20521764)
• This study demonstrated a hitherto-undescribed role of MetAP2 in definitive hematopoiesis and a possible link to noncanonical Wnt and ERK signaling. (PMID:21937698)
• Increased expression of METAP2 is associated with pilocytic astrocytoma. (PMID:23161775)
• The activity of unmodified, nitrated and oxidised METAP2 was assessed and it was found that nitration significantly reduced its ability to cleave a chromogenic substrate. Mass spectrometry analysis identified Tyr336 as a nitrated residue in METAP2. (PMID:24041691)
• Data indicate that methionine aminopeptidase 2 (MetAP2) contains a single disulfide bond that exists in oxidized and reduced states and influences enzyme function. (PMID:24700462)
• Nt-acetylation prevents the excision of the initiator methionine by MetAP2. (PMID:25886145)
• Suggest MetAP2 as important regulator of proliferation/apoptosis in non-small cell lung cancers. (PMID:26935506)
• MetAP1 and MetAP2 have roles in driving cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state (PMID:27542228)
• Results show that methionine aminopeptidase-2 (MetAP2) regulates angiogenesis in glioblastoma and identify MetAP2-specific substrates that may serve as candidates for clinical assay development. (PMID:29116484)
• CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2. (PMID:32922205)
• In Vivo Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification. (PMID:33637565)
• Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons. (PMID:38335281)
• Using bovine cell extract, fumagillin was found to be bound by methionine aminopeptidase (MetAP-2). (PMID:9177176)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	metap2b	ENSDARG00000102571
mus_musculus	Metap2	ENSMUSG00000036112
rattus_norvegicus	Metap2-ps1	ENSRNOG00000015772
rattus_norvegicus	Metap2	ENSRNOG00000021881
caenorhabditis_elegans	F53B6.5	WBGENE00009960
caenorhabditis_elegans		WBGENE00012075

Paralogs (7): XPNPEP1 (ENSG00000108039), XPNPEP2 (ENSG00000122121), PEPD (ENSG00000124299), METAP1 (ENSG00000164024), PA2G4 (ENSG00000170515), METAP1D (ENSG00000172878), XPNPEP3 (ENSG00000196236)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1929701) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 14 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal vascular development	1
decreased cell proliferation	1
abnormal blood vessel morphology	1
absent mesoderm	1
failure to gastrulate	1
decreased embryo size	1
embryonic growth arrest	1
disorganized embryonic tissue	1
abnormal dorsal aorta morphology	1
decreased vascular endothelial cell number	1
embryonic lethality between somite formation and embryo turning, complete penetrance	1
embryonic lethality during organogenesis, complete penetrance	1
abnormal intersomitic vessel morphology	1
embryo tissue necrosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Saccharomyces cerevisiae YJM789	A6ZKL2	100.0%	Diamond
Aspergillus fumigatus A1163	B0XTJ7	100.0%	Diamond
Saccharomyces cerevisiae RM11-1a	B3LNM2	100.0%	Diamond
Saccharomyces cerevisiae AWRI1631	B5VDQ0	100.0%	Diamond
Aspergillus flavus NRRL3357	B8NLL0	100.0%	Diamond
Blastomyces dermatitidis ER-3	C5GCN0	100.0%	Diamond
Blastomyces gilchristii SLH14081	C5JW60	100.0%	Diamond
Saccharomyces cerevisiae JAY291	C7GSF3	100.0%	Diamond
Saccharomyces cerevisiae EC1118	C8Z3V4	100.0%	Diamond
Saccharomyces cerevisiae S288C	P38174	100.0%	Diamond
Aspergillus oryzae RIB40	Q2U6H2	100.0%	Diamond
Aspergillus fumigatus Af293	Q4WAY7	100.0%	Diamond
Paracoccidioides brasiliensis Pb03	C0SIM8	99.6%	Diamond
Paracoccidioides brasiliensis Pb18	C1GLM4	99.6%	Diamond
Candida albicans WO-1	C4YSA9	99.6%	Diamond
Candida albicans SC5314	Q59LF9	99.6%	Diamond
Trichophyton benhamiae CBS 112371	D4B2G3	98.9%	Diamond
Trichophyton verrucosum HKI 0517	D4DE65	98.9%	Diamond
Paracoccidioides lutzii Pb01	C1HAB2	98.7%	Diamond
Botrytis cinerea B05.10	A6RTU0	98.0%	Diamond
Sclerotinia sclerotiorum 1980 UF-70	A7EZ86	98.0%	Diamond
Pyrenophora teres f. teres 0-1	E3RCY7	96.2%	Diamond
Nannizzia gypsea CBS 118893	E5R3Z8	96.2%	Diamond
Sordaria macrospora k-hell	D1ZEN1	96.1%	Diamond
Neurospora crassa OR74A	Q7S7L7	96.1%	Diamond
Pyrenophora tritici-repentis Pt-1C-BFP	B2W1N6	96.0%	Diamond
Bos taurus	Q3ZC89	96.0%	Diamond
Histoplasma mississippiense	A6RGC8	95.7%	Diamond
Histoplasma capsulatum G186AR	C0NX86	95.7%	Diamond
Aspergillus clavatus NRRL 1	A1CH02	95.1%	Diamond
Aspergillus fischeri NRRL 181	A1CXT5	95.1%	Diamond
Microsporum canis CBS 113480	C5FF46	94.4%	Diamond
Talaromyces marneffei ATCC 18224	B6Q1N3	93.7%	Diamond
Talaromyces stipitatus ATCC 10500	B8LUH2	93.7%	Diamond
Aspergillus terreus NIH2624	Q0CL94	93.4%	Diamond
Penicillium rubens Wisconsin 54-1255	B6HTQ4	92.2%	Diamond
Pyrococcus horikoshii OT3	O58362	91.9%	Diamond
Pyrococcus abyssi GE5	Q9UYT4	91.9%	Diamond
Aspergillus nidulans FGSC A4	Q5B4X6	91.8%	Diamond
Candida tropicalis MYA-3404	C5M8M4	91.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
NTN4	protein-coding	59277
USP44	protein-coding	84101
MIR3685	ncRNA	100500802
LINC02410	ncRNA	105369920
SNRPF-DT	ncRNA	105369921

Protein

Protein identifiers

Methionine aminopeptidase 2 — P50579 (reviewed: P50579)

Alternative names: Initiation factor 2-associated 67 kDa glycoprotein, Peptidase M

All UniProt accessions (8): A0A140VJE3, F8VQZ7, F8VRR3, F8VSC4, P50579, F8VY03, F8VZX9, G3V1U3

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). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo. Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.

Subunit / interactions. Interacts strongly with the eIF-2 gamma-subunit EIF2S3. Binds EIF2S1 at low magnesium concentrations.

Subcellular location. Cytoplasm.

Post-translational modifications. Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc) residues. O-glycosylation is required for EIF2S1 binding.

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 cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site. Also manganese has been proposed to be the physiological cofactor for human METAP2.

Similarity. Belongs to the peptidase M24A family. Methionine aminopeptidase eukaryotic type 2 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P50579-1	1	yes
P50579-2	2
P50579-3	3

RefSeq proteins (4): NP_001304111, NP_001304112, NP_001317175, NP_006829* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000994	Pept_M24	Domain
IPR001714	Pept_M24_MAP	Family
IPR002468	Pept_M24A_MAP2	Family
IPR018349	Pept_M24A_MAP2_BS	Binding_site
IPR036005	Creatinase/aminopeptidase-like	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR050247

Pfam: PF00557

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 (61 total): strand 17, helix 15, binding site 9, modified residue 5, compositionally biased region 4, splice variant 3, glycosylation site 2, turn 2, initiator methionine 1, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

showing 30 of 40 structures by resolution:

PDB	Title	Method	Resolution (Å)
5D6E	Structure of human methionine aminopeptidase 2 with covalent spiroepoxytriazole inhibitor …	X-RAY DIFFRACTION	1.49
5D6F	Structure of human methionine aminopeptidase-2 complexed with spiroepoxytriazole …	X-RAY DIFFRACTION	1.55
1B6A	HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH TNP-470	X-RAY DIFFRACTION	1.6
1QZY	Human Methionine Aminopeptidase in complex with bengamide inhibitor LAF153 and cobalt	X-RAY DIFFRACTION	1.6
5JFR	Potent, Reversible MetAP2 Inhibitors via Fragment Based Drug Discovery	X-RAY DIFFRACTION	1.6
6QEJ	CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR …	X-RAY DIFFRACTION	1.62
1YW9	h-MetAP2 complexed with A849519	X-RAY DIFFRACTION	1.64
5LYW	CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX; WITH AN INHIBITOR …	X-RAY DIFFRACTION	1.69
8OXG	Crystal structure of human methionine aminopeptidase-2 complexed with …	X-RAY DIFFRACTION	1.73
5CLS	Structure of human methionine aminopeptidase-2 complexed with spiroepoxytriazole …	X-RAY DIFFRACTION	1.75
6QEF	CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR …	X-RAY DIFFRACTION	1.79
1B59	COMPLEX OF HUMAN METHIONINE AMINOPEPTIDASE-2 COMPLEXED WITH OVALICIN	X-RAY DIFFRACTION	1.8
1BN5	HUMAN METHIONINE AMINOPEPTIDASE 2	X-RAY DIFFRACTION	1.8
1BOA	HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH ANGIOGENESIS INHIBITOR FUMAGILLIN	X-RAY DIFFRACTION	1.8
5JHU	Potent, Reversible MetAP2 Inhibitors via FBDD	X-RAY DIFFRACTION	1.8
6QED	CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX; WITH AN INHIBITOR …	X-RAY DIFFRACTION	1.8
6QEI	CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR …	X-RAY DIFFRACTION	1.8
1YW7	h-MetAP2 complexed with A444148	X-RAY DIFFRACTION	1.85
1KQ9	Human methionine aminopeptidase type II in complex with L-methionine	X-RAY DIFFRACTION	1.9
1R58	Crystal Structure of MetAP2 complexed with A357300	X-RAY DIFFRACTION	1.9
2ADU	Human Methionine Aminopeptidase Complex with 4-Aryl-1,2,3-triazole Inhibitor	X-RAY DIFFRACTION	1.9
2OAZ	Human Methionine Aminopeptidase-2 Complexed with SB-587094	X-RAY DIFFRACTION	1.9
5LYX	CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX; WITH AN INHIBITOR …	X-RAY DIFFRACTION	1.9
7A16	CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR …	X-RAY DIFFRACTION	1.9
2GA2	h-MetAP2 complexed with A193400	X-RAY DIFFRACTION	1.95
1KQ0	Human methionine aminopeptidase type II in complex with D-methionine	X-RAY DIFFRACTION	2
1R5G	Crystal Structure of MetAP2 complexed with A311263	X-RAY DIFFRACTION	2
7A12	CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR …	X-RAY DIFFRACTION	2
7A13	CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR …	X-RAY DIFFRACTION	2.04
6QEG	CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR …	X-RAY DIFFRACTION	2.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50579-F1	86.07	0.78

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane; primary cilium; primary cilium tip

Antibody reliability (HPA): IH enhanced · IF approved

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 (9)

Position	Role
262	a divalent metal cation
331	a divalent metal cation
339	substrate
364	a divalent metal cation
459	a divalent metal cation
231	substrate
251	a divalent metal cation

Post-translational modifications (5)

Type	Positions
N-acetylalanine	2
Phosphoserine	45, 60, 63, 74

Glycosylation sites (2)

Type	Positions
O-linked (glcnac) serine	60, 63

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

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

MSigDB gene sets: 201 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOMF_METALLOPEPTIDASE_ACTIVITY, PEREZ_TP63_TARGETS, GOBP_TRANSLATIONAL_INITIATION, GNF2_RRM1, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CTAGGAA_MIR384, GOBP_PROTEIN_MATURATION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GNF2_SMC4L1, HESS_TARGETS_OF_HOXA9_AND_MEIS1_UP, AAAGACA_MIR511, GARY_CD5_TARGETS_DN

GO Biological Process (3): regulation of translational initiation (GO:0006446), protein processing (GO:0016485), proteolysis (GO:0006508)

GO Molecular Function (9): RNA binding (GO:0003723), aminopeptidase activity (GO:0004177), initiator methionyl aminopeptidase activity (GO:0004239), metalloexopeptidase activity (GO:0008235), metal ion binding (GO:0046872), metalloaminopeptidase activity (GO:0070006), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

3 top-level categories:

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

GO top-level categories

18 GO namespaces:

Category	Terms
exopeptidase activity	2
aminopeptidase activity	2
cellular anatomical structure	2
translational initiation	1
regulation of translation	1
proteolysis	1
protein maturation	1
protein metabolic process	1
nucleic acid binding	1
metallopeptidase activity	1
cation binding	1
metalloexopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
protein processing	BP	direct assay
regulation of translational initiation	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
RNA binding	MF	high-throughput assay
aminopeptidase activity	MF	direct assay
metalloexopeptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,607 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
METAP2	METAP1	P53582	963
METAP2	CRBN	Q96SW2	638
METAP2	METAP1D	Q6UB28	523
METAP2	SKP1	P34991	512
METAP2	RTL10	Q7L3V2	486
METAP2	DDX18	Q9NVP1	470
METAP2	ZBTB17	Q13105	464
METAP2	ODC1	P11926	458
METAP2	LIN28A	Q9H9Z2	448
METAP2	DPP3	Q9NY33	438
METAP2	EIF2S1	P05198	436
METAP2	GLS2	Q9UI32	433
METAP2	TRIB1	Q96RU8	427
METAP2	GLS	O94925	427
METAP2	SEH1L	Q96EE3	427

IntAct

Human interaction partners of METAP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

18 partners by confidence:

Partner	Interaction type	MIscore	Records
FCRL2	physical association	0.590	2
DRD4	physical association	0.560	3
PLPPR2	association	0.530	2
TMEM213	association	0.530	2
RDH14	physical association	0.500	1
ATP5PO	physical association	0.400	1
PCBD2	physical association	0.400	1
PDE4A	physical association	0.400	1
PTCHD1	physical association	0.370	1
SLC25A25	association	0.350	3
DNAJC27	association	0.350	2
RGS2	association	0.350	2
EIF3CL	association	0.350	1
GCG	association	0.350	1
LAD1	association	0.350	1
SEZ6	association	0.350	1
TEKT2	association	0.350	1
DSCAM	physical association	0.000	1

BioGRID (336 interactions; top human partners by supporting records): C1QB (Affinity Capture-MS; 3 records), GNAS (Affinity Capture-MS; 3 records), LPPR2 (Affinity Capture-MS; 3 records), PLIN5 (Affinity Capture-MS; 3 records), ASB6 (Affinity Capture-MS; 2 records), C1QTNF9 (Affinity Capture-MS; 2 records), CCT2 (Affinity Capture-MS; 2 records), CCT3 (Affinity Capture-MS; 2 records), CCT7 (Affinity Capture-MS; 2 records), CUL5 (Affinity Capture-MS; 2 records), DDX28 (Affinity Capture-MS; 2 records), DLK2 (Affinity Capture-MS; 2 records), EIF2AK2 (Affinity Capture-Western; 2 records), FCRL2 (Affinity Capture-MS; 2 records), GPBP1L1 (Affinity Capture-MS; 2 records)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ METAP2-PDE4A complex	2	METAP2, PDE4A

Disease & clinical

Genetic variants

Variant evidence for METAP2: 325 ClinVar records (1 pathogenic / likely pathogenic); 26 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	241
Likely benign	23
Benign	17

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
150477	GRCh38/hg38 2q33.3-34(chr2:207058886-211245603)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore METAP2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 3,632):

Position(s)	Effect	Δscore	Sites
12:95474331	donor_loss	1.0000	2
12:95476069–95476070	acceptor_loss	1.0000	6
12:95476179–95476180	donor_loss	1.0000	5
12:95483290	donor_gain	1.0000
12:95483295	donor_gain	1.0000
12:95495132	donor_gain	1.0000
12:95504063	acceptor_loss	1.0000	2
12:95504162	donor_loss	1.0000
12:95511889–95511891	acceptor_gain	1.0000	2
12:95511893–95511894	acceptor_loss	1.0000	6

AlphaMissense

1,698 missense substitutions predicted likely pathogenic (of 3,140 scored), across 343 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M308	9	0.965	0.999
M355	9	0.963	0.999
M384	9	0.955	0.991
F219	8	0.999	1.000
D251	8	0.999	1.000
D262	8	0.999	1.000
H331	8	0.999	1.000
H339	8	0.999	1.000
H231	8	0.998	1.000
F366	8	0.997	1.000
H382	8	0.997	1.000
D449	8	0.997	1.000
F415	8	0.994	1.000
H176	8	0.993	0.999
H460	8	0.991	0.998
D238	8	0.988	0.999
D246	8	0.986	0.999
D477	8	0.984	0.996
D294	8	0.982	0.996
F410	8	0.977	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

7 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.94e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.05e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000273
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000323
Kidney Chromophobe (TCGA)	unfavorable	0.000458
Stomach Adenocarcinoma (TCGA)	unfavorable	0.000753
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	0.000885

Disease associations

OMIM: gene MIM:601870 | disease phenotypes:

GWAS associations

26 associations:

Study	Trait	p-value
GCST90002386_64	High light scatter reticulocyte percentage of red cells	3e-53
GCST90002385_479	High light scatter reticulocyte count	1e-51
GCST90002405_327	Reticulocyte count	3e-32
GCST90013421_25	Left-handedness	2e-30
GCST90013407_53	Liver enzyme levels (gamma-glutamyl transferase)	2e-24
GCST010700_2	Cortical thickness (MOSTest)	9e-21
GCST010701_83	Cortical surface area (MOSTest)	3e-19
GCST004628_145	Immature fraction of reticulocytes	4e-17
GCST007614_23	C-reactive protein levels	5e-14
GCST90010427_4	Left–right brain asymmetry	1e-10
GCST007325_306	General risk tolerance (MTAG)	3e-10
GCST010698_87	Subcortical volume (min-P)	2e-9
GCST007324_92	Adventurousness	9e-9
GCST010699_19	Brain morphology (min-P)	1e-8
GCST008819_1	Handedness (left-handed vs. right-handed)	3e-8
GCST007592_1	Handedness (Left-handed vs. non-left-handed)	4e-8
GCST010703_163	Brain morphology (MOSTest)	4e-8
GCST006585_439	Blood protein levels	5e-8
GCST008818_3	Handedness (Left-handed vs. non-left-handed)	5e-8
GCST010702_50	Subcortical volume (MOSTest)	5e-8
GCST009391_1656	Metabolite levels	3e-7
GCST008163_264	Height	6e-7
GCST90013411_1	Skin and soft tissue infections	2e-6
GCST008103_30	Bipolar disorder	8e-6
GCST008158_82	Body mass index	8e-6
GCST011741_45	LDL cholesterol levels in HIV infection	1e-5

EFO canonical traits (from GWAS)

11 canonical traits:

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0008579	risk-taking behaviour
EFO:0009902	handedness
EFO:0004458	C-reactive protein measurement
EFO:0004340	body mass index
EFO:0010422	triacylglycerol 54:4 measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:1001489	skin and soft tissue Staphylococcus aureus infection

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3831223 (PROTEIN FAMILY), CHEMBL3922 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the METAP2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
BELORANIB	Small molecule	3
ACLIMOSTAT	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 105,037 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

10 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL497	CLIOQUINOL	4	13,056
CHEMBL1454910	NITROXOLINE	4	1,882
CHEMBL625	THIABENDAZOLE	4	59,017
CHEMBL4297504	BELORANIB	3	447
CHEMBL51085	EBSELEN	3	13,356
CHEMBL1170610	BENZOXIQUINE	2	512
CHEMBL225164	CLOXYQUIN	2	3,915
CHEMBL32838	FUMAGILLIN	2	10,167
CHEMBL424278	O-CHLOROACETYLCARBAMOYLFUMAGILLOL	2	2,416
CHEMBL3527358	PPI-2458	1	269

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M24: Methionyl aminopeptidase

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
BAY-277	Inhibition	8.24	pIC50
XMT-1191	Inhibition	8.0	pIC50
M8891	Inhibition	7.27	pIC50
nitroxoline	Inhibition	7.26	pIC50

Binding affinities (BindingDB)

932 measured of 1053 human assays (1060 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-(benzylsulfanyl)-N-(2-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	0.04 nM
N-[5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]pyridin-3-amine	KI	0.04 nM
5-(benzylsulfanyl)-N-(4-methoxyphenyl)-4H-1,2,4-triazol-3-amine	KI	0.05 nM
5-(benzylsulfanyl)-N-(4-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	0.07 nM
FOS-69	IC50	0.1 nM
5-{[(2-fluorophenyl)methyl]sulfanyl}-N-(4-methoxyphenyl)-4H-1,2,4-triazol-3-amine	KI	0.13 nM
5-[(3-methylbut-2-en-1-yl)sulfanyl]-N-(2-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	0.15 nM
N-(4-methoxyphenyl)-5-[(3-methylbut-2-en-1-yl)sulfanyl]-4H-1,2,4-triazol-3-amine	KI	0.16 nM
5-{[(2-fluorophenyl)methyl]sulfanyl}-N-(2-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	0.23 nM
N-(5-{[(2-fluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pyridin-3-amine	KI	0.3 nM
Carbamic acid (3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methyl-but-2-enyl)-oxiranyl]-1-oxa-spiro[2.5]oct-6-yl ester	IC50	0.39 nM
Ovalicin	IC50	0.4 nM
4-Hydroxy-5-methoxy-4-[(2S,3R)-2-methyl-3-(3-methyl-but-2-enyl)-oxiranyl]-1-oxa-spiro[2.5]octan-6-one	IC50	0.4 nM
methyl 4-[(5-{[(2-fluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)amino]benzoate	KI	0.41 nM
5-(benzylsulfanyl)-N-(4-chlorophenyl)-4H-1,2,4-triazol-3-amine	KI	0.43 nM
Acetyl-carbamic acid (3R,4S,5S,6R)-5-methoxy-4-[(R)-2-(R)-methyl-3-(3-methyl-but-2-enyl)-oxiranyl]-1-oxa-spiro[2.5]oct-6-yl ester	IC50	0.43 nM
5-(benzylsulfanyl)-N-phenyl-4H-1,2,4-triazol-3-amine	KI	0.5 nM
methyl 4-({5-[(3-methylbut-2-en-1-yl)sulfanyl]-4H-1,2,4-triazol-3-yl}amino)benzoate	KI	0.5 nM
N-(5-{[(3,4-difluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pyridin-3-amine	KI	0.5 nM
Acetic acid (3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methyl-but-2-enyl)-oxiranyl]-1-oxa-spiro[2.5]oct-6-yl ester	IC50	0.51 nM
N-(4-chlorophenyl)-5-[(3-methylbut-2-en-1-yl)sulfanyl]-4H-1,2,4-triazol-3-amine	KI	0.52 nM
N-(4-chlorophenyl)-5-{[(2-fluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-amine	KI	0.61 nM
5-{[(2-fluorophenyl)methyl]sulfanyl}-N-(4-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	0.65 nM
methyl 4-{[5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]amino}benzoate	KI	0.7 nM
N-phenyl-5-[(thiophen-2-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-amine	KI	0.75 nM
methyl 4-[(5-{[(5-methyl-1,2-oxazol-3-yl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)amino]benzoate	KI	0.8 nM
4-Ethyl-piperazine-1-carboxylic acid (3R,4S,5S,6R)-4-{1-[(E)-cyclohexylmethoxyimino]-ethyl}-5-methoxy-1-oxa-spiro[2.5]oct-6-yl ester	IC50	0.8 nM
N-(3,4-dimethoxyphenyl)-5-[(3-methylbut-2-en-1-yl)sulfanyl]-4H-1,2,4-triazol-3-amine	KI	0.9 nM
methyl 4-({5-[(pyridin-2-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}amino)benzoate	KI	0.9 nM
methyl 4-({5-[(pyridin-4-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}amino)benzoate	KI	0.9 nM
CHEMBL137766	IC50	0.96 nM
5-[(3-methylbut-2-en-1-yl)sulfanyl]-N-phenyl-4H-1,2,4-triazol-3-amine	KI	1 nM
(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl N-(2-chloroacetyl)carbamate	IC50	1 nM
5-(4-iodophenyl)-1H-1,2,3-triazole	KI	1 nM
5-(3,4-dibromophenyl)-1H-1,2,3-triazole	KI	1 nM
AGM-1470	IC50	1 nM
Deca-2,4,6,8-tetraenedioic acid mono-{5-methoxy-4-[2-methyl-3-(3-methyl-but-2-enyl)-oxiranyl]-1-oxa-spiro[2.5]oct-6-yl} ester	IC50	1 nM
5-[(3-methylbut-2-en-1-yl)sulfanyl]-N-(4-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	1.2 nM
Acetic acid (3R,4S,5S,6R)-4-{1-[(E)-benzyloxyimino]-ethyl}-5-methoxy-1-oxa-spiro[2.5]oct-6-yl ester	IC50	1.2 nM
Carbamic acid (3R,4S,5S,6R)-4-{1-[(E)-benzyloxyimino]-ethyl}-5-methoxy-1-oxa-spiro[2.5]oct-6-yl ester	IC50	1.2 nM
N-(3,4-dimethoxyphenyl)-5-{[(2-fluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-amine	KI	1.3 nM
methyl 4-[(5-{[(3,4-difluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)amino]benzoate	KI	1.3 nM
7-[2-(3-hydroxypyrrolidin-1-yl)-3-pyridinyl]-5-(2,2,2-trifluoroethyl)-2,3,3a,5a,6,7,8,9,9a,9b-decahydro-1H-pyrazolo[4,3-c]quinolin-4-one	IC50	1.46 nM	US-9169246: Pyrazoloquinolinone derivatives, preparation thereof and therapeutic use thereof
N-(4-chlorophenyl)-5-{[(3,4-difluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-amine	KI	1.5 nM
N-(5-{[(5-methyl-1,2-oxazol-3-yl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pyridin-3-amine	KI	1.5 nM
N-(4-methoxyphenyl)-5-{[(5-methyl-1,2-oxazol-3-yl)methyl]sulfanyl}-4H-1,2,4-triazol-3-amine	KI	1.6 nM
(3S)-1-[2-[(3R,5S,6R)-5-Amino-6-(2,5-difluorophenyl)tetrahydropyran-3-yl]triazol-4-yl]-N-[(3-chloro-5-fluoro-phenyl)methyl]-3-hydroxy-2-oxo-pyrrolidine-3-carboxamide, hydrochloride	IC50	1.67 nM	US-10807971: Pyrrolidinone compounds
5-(benzylsulfanyl)-N-(3,4-dimethoxyphenyl)-4H-1,2,4-triazol-3-amine	KI	1.7 nM
N-(5-{[(2-methylphenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pyridin-3-amine	KI	1.7 nM
Carbamic acid (3R,4S,5S,6R)-4-((E)-1,5-dimethyl-hexa-1,4-dienyl)-5-methoxy-1-oxa-spiro[2.5]oct-6-yl ester	IC50	1.7 nM

ChEMBL bioactivities

1342 potent at pChembl≥5 of 1426 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	Ki	0.04	nM	CHEMBL241829
10.40	Ki	0.04	nM	CHEMBL243306
10.30	Ki	0.05	nM	CHEMBL397477
10.15	Ki	0.07079	nM	CHEMBL243111
10.15	Ki	0.07	nM	CHEMBL243111
10.02	EC50	0.095	nM	PPI-2458
9.89	Ki	0.13	nM	CHEMBL242435
9.82	Ki	0.15	nM	CHEMBL245022
9.80	Ki	0.16	nM	CHEMBL245226
9.80	Ki	0.16	nM	CHEMBL4475680
9.64	Ki	0.23	nM	CHEMBL389087
9.52	EC50	0.3	nM	CHEMBL3527591
9.52	Ki	0.3	nM	CHEMBL242050
9.41	IC50	0.39	nM	CHEMBL176975
9.40	IC50	0.4	nM	OVALICIN
9.39	Ki	0.41	nM	CHEMBL242875
9.37	Ki	0.43	nM	CHEMBL242028
9.37	IC50	0.43	nM	CHEMBL368349
9.30	Ki	0.5	nM	CHEMBL243303
9.30	Ki	0.5	nM	CHEMBL242051
9.30	Ki	0.5	nM	CHEMBL243101
9.29	IC50	0.51	nM	CHEMBL172123
9.28	Ki	0.52	nM	CHEMBL242891
9.21	Ki	0.61	nM	CHEMBL242462
9.20	IC50	0.63	nM	FUMAGILLIN
9.19	Ki	0.65	nM	CHEMBL243320
9.15	Ki	0.7	nM	CHEMBL242663
9.12	Ki	0.75	nM	CHEMBL243305
9.10	Ki	0.8	nM	CHEMBL396988
9.10	Ki	0.8	nM	CHEMBL243305
9.10	IC50	0.8	nM	CHEMBL367938
9.06	Kd	0.88	nM	CHEMBL4451402
9.05	Ki	0.9	nM	CHEMBL430001
9.05	Ki	0.9	nM	CHEMBL242876
9.05	Ki	0.9	nM	CHEMBL242447
9.05	Ki	0.9	nM	CHEMBL4451402
9.02	IC50	0.96	nM	CHEMBL137766
9.00	Ki	1	nM	CHEMBL364051
9.00	Ki	1	nM	CHEMBL195915
9.00	IC50	1	nM	O-CHLOROACETYLCARBAMOYLFUMAGILLOL
9.00	Ki	1	nM	O-CHLOROACETYLCARBAMOYLFUMAGILLOL
9.00	Ki	1	nM	CHEMBL230640
9.00	IC50	1	nM	FUMAGILLIN
8.94	Kd	1.14	nM	CHEMBL4448724
8.92	IC50	1.2	nM	FUMAGILLIN
8.92	Ki	1.202	nM	CHEMBL398002
8.92	Ki	1.2	nM	CHEMBL398002
8.92	IC50	1.2	nM	CHEMBL172883
8.92	IC50	1.2	nM	CHEMBL174250
8.89	EC50	1.3	nM	CHEMBL3526173

PubChem BioAssay actives

1161 with measured affinity, of 1674 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
N-(3-benzylsulfanyl-1H-1,2,4-triazol-5-yl)pyridin-3-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	<0.0001	uM
3-benzylsulfanyl-N-(2-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	<0.0001	uM
3-(3-methylbut-2-enylsulfanyl)-N-(2-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0001	uM
[(3S,4R,5R,6R)-4-hydroxy-5-methoxy-4-[(2R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] 4-chlorobutanoate	1799439: Enzymatic Assay from Article 10.1016/s1074-5521(97)90198-8: “Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin.”	ic50	0.0001	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-[(2R)-1-amino-3-methyl-1-oxobutan-2-yl]carbamate	1223628: Inhibition of MetAP2 activity in HUVEC assessed as inhibition of cell proliferation by MTT assay	ec50	0.0001	uM
3-benzylsulfanyl-N-(4-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0001	uM
3-[(2-fluorophenyl)methylsulfanyl]-N-(4-methoxyphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0001	uM
3-benzylsulfanyl-N-(4-methoxyphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0001	uM
3-[(2-fluorophenyl)methylsulfanyl]-N-(2-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0002	uM
N-(4-methoxyphenyl)-3-(3-methylbut-2-enylsulfanyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0002	uM
(3S)-N-[(3-chloro-5-fluorophenyl)methyl]-3-hydroxy-2-oxo-1-(2-oxo-3,4-dihydro-1H-quinolin-6-yl)pyrrolidine-3-carboxamide	1617491: Inhibition of 5-[(S)-3-(3-Chloro-5-fluoro-benzylcarbamoyl)-3-hydroxy-2-oxopyrrolidin-1-yl]-1H-indole-2-carboxylic Acid (3-Amino-propyl)-amide-Dy647 binding to recombinant full length N-terminal GFP-fused MetAP2 (unknown origin) expressed in HEK293 cells by Cheng-Prusoff equation analysis	ki	0.0002	uM
N-[3-[(2-fluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]pyridin-3-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0003	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-[(2R)-1-amino-3-hydroxy-3-methyl-1-oxobutan-2-yl]carbamate	1223628: Inhibition of MetAP2 activity in HUVEC assessed as inhibition of cell proliferation by MTT assay	ec50	0.0003	uM
(3S,4R,5S)-4-hydroxy-5-methoxy-4-[(2S,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-one	424804: Inhibition of methionine aminopeptidase 2	ic50	0.0004	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] carbamate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0004	uM
methyl 4-[[3-[(2-fluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0004	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-carbonochloridoylcarbamate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0004	uM
(3S,4R,5S)-4-hydroxy-5-methoxy-4-[(2R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-one	1799439: Enzymatic Assay from Article 10.1016/s1074-5521(97)90198-8: “Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin.”	ic50	0.0004	uM
3-benzylsulfanyl-N-(4-chlorophenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0004	uM
N-[3-[(3,4-difluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]pyridin-3-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0005	uM
methyl 4-[[3-(3-methylbut-2-enylsulfanyl)-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0005	uM
N-(4-chlorophenyl)-3-(3-methylbut-2-enylsulfanyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0005	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] acetate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0005	uM
3-benzylsulfanyl-N-phenyl-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0005	uM
3-[(2-fluorophenyl)methylsulfanyl]-N-(4-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0006	uM
Fumagillin	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0006	uM
N-(4-chlorophenyl)-3-[(2-fluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0006	uM
methyl 4-[(3-benzylsulfanyl-1H-1,2,4-triazol-5-yl)amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0007	uM
N-phenyl-3-(thiophen-2-ylmethylsulfanyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0008	uM
methyl 4-[[3-[(5-methyl-1,2-oxazol-3-yl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0008	uM
[(3R,4S,5S,6R)-4-[(E)-N-(cyclohexylmethoxy)-C-methylcarbonimidoyl]-5-methoxy-1-oxaspiro[2.5]octan-6-yl] 4-ethylpiperazine-1-carboxylate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0008	uM
(3S)-N-[(3,5-difluorophenyl)methyl]-3-hydroxy-2-oxo-1-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolidine-3-carboxamide	1617491: Inhibition of 5-[(S)-3-(3-Chloro-5-fluoro-benzylcarbamoyl)-3-hydroxy-2-oxopyrrolidin-1-yl]-1H-indole-2-carboxylic Acid (3-Amino-propyl)-amide-Dy647 binding to recombinant full length N-terminal GFP-fused MetAP2 (unknown origin) expressed in HEK293 cells by Cheng-Prusoff equation analysis	ki	0.0009	uM
N-(3,4-dimethoxyphenyl)-3-(3-methylbut-2-enylsulfanyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0009	uM
methyl 4-[[3-(pyridin-2-ylmethylsulfanyl)-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0009	uM
methyl 4-[[3-(pyridin-4-ylmethylsulfanyl)-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0009	uM
3-(3-methylbut-2-enylsulfanyl)-N-phenyl-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0010	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-(2-chloroacetyl)carbamate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0010	uM
[(3R,5S,6R)-5-methoxy-4-[(2S)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-(2-chloroacetyl)carbamate	1799439: Enzymatic Assay from Article 10.1016/s1074-5521(97)90198-8: “Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin.”	ic50	0.0010	uM
4-(4-iodophenyl)-2H-triazole	1797630: Enzyme Inhibition Assay from Article 10.1021/jm050408c: “4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo.”	ki	0.0010	uM
4-(3,4-dibromophenyl)-2H-triazole	1797630: Enzyme Inhibition Assay from Article 10.1021/jm050408c: “4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo.”	ki	0.0010	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] (E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate	1551719: Inhibition of human MetAP2	ic50	0.0010	uM
(3S)-N-[(3-chloro-5-fluorophenyl)methyl]-3-hydroxy-2-oxo-1-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolidine-3-carboxamide	1617492: Inhibition of 5-[(S)-3-(3-Chloro-5-fluoro-benzylcarbamoyl)-3-hydroxy-2-oxopyrrolidin-1-yl]-1H-indole-2-carboxylic Acid (3-Amino-propyl)-amide-Dy647 binding to recombinant full length N-terminal GFP-fused MetAP2 (unknown origin) expressed in HEK293 cells by FCCS analysis	kd	0.0011	uM
3-(3-methylbut-2-enylsulfanyl)-N-(4-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0012	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(E)-C-methyl-N-phenylmethoxycarbonimidoyl]-1-oxaspiro[2.5]octan-6-yl] acetate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0012	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(E)-C-methyl-N-phenylmethoxycarbonimidoyl]-1-oxaspiro[2.5]octan-6-yl] carbamate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0012	uM
[(3R,4S,5S,6R)-4-[(2R,3R)-3-[[(2R)-3,3-dimethyloxiran-2-yl]methyl]-2-methyloxiran-2-yl]-5-methoxy-1-oxaspiro[2.5]octan-6-yl] N-[(2R)-1-amino-3-methyl-1-oxobutan-2-yl]carbamate	1223628: Inhibition of MetAP2 activity in HUVEC assessed as inhibition of cell proliferation by MTT assay	ec50	0.0013	uM
methyl 4-[[3-[(3,4-difluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0013	uM
N-(3,4-dimethoxyphenyl)-3-[(2-fluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0013	uM
N-[3-[(5-methyl-1,2-oxazol-3-yl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]pyridin-3-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0015	uM
N-(4-chlorophenyl)-3-[(3,4-difluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0015	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	3
fumagillin	affects cotreatment, decreases activity, decreases metabolic processing	2
Cobalt	increases activity, affects binding	2
Gold	decreases expression	2
Triazoles	decreases activity, decreases reaction	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
nitroxoline	decreases activity	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
tetrahydropalmatine	decreases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases activity	1
manganese chloride	decreases reaction, increases activity, decreases activity	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
pinosylvin	decreases expression	1
glycidamide	increases expression	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
3,4,5-trihydroxy-2–methoxy-8,8-dimethyl-N-(hexahydro-2-oxo-6-(cyclohexylcarbonyl)oxy-2H-azepin-3-yl)non-6-enamide	affects metabolic processing, affects cotreatment, decreases activity, decreases metabolic processing, affects binding	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	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1

ChEMBL screening assays

111 unique, capped per target: 105 binding, 5 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4334276	ADMET	Stability in pH 2 HCl assessed as aminopeptidase (unknown origin)-mediated compound hydrolysis by measuring parent compound remaining at 200 uM up to 6 hrs by RP-HPLC analysis	Astratides: Insulin-Modulating, Insecticidal, and Antifungal Cysteine-Rich Peptides from Astragalus membranaceus. — *J Nat Prod*
CHEMBL1027137	Binding	Inhibition of methionine aminopeptidase 2	A selective account of effective paradigms and significant outcomes in the discovery of inspirational marine natural products. — *J Nat Prod*
CHEMBL5464009	Functional	Degradation in HT1080 cells (CE) (Capillary electrophoresis (CE))	Data for DCP probe BAY-277

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 90 trials:

NCT	Phase	Status	Title
NCT00069550	Phase 3	UNKNOWN	Independent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome
NCT00261508	Phase 3	COMPLETED	A Study of the Effectiveness and Safety of Risperidone Versus Placebo in the Treatment of Children With Autistic Disorder and Other Pervasive Developmental Disorders (PDD)
NCT03848832	Phase 3	TERMINATED	Efficacy and Safety of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome
NCT03941444	Phase 3	COMPLETED	ANAVEX2-73 Study in Patients With Rett Syndrome
NCT04181723	Phase 3	COMPLETED	Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (LAVENDER™)
NCT04252586	Phase 3	TERMINATED	A Long-term Safety Study of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome
NCT04279314	Phase 3	COMPLETED	Open-Label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome
NCT04776746	Phase 3	TERMINATED	Open-Label Extension Study of Trofinetide for Rett Syndrome
NCT05606614	Phase 3	ACTIVE_NOT_RECRUITING	A Phase 1/2/3 Study of TSHA-102 Gene Therapy in Females With Rett Syndrome (REVEAL Pivotal Study)
NCT05898620	Phase 3	ACTIVE_NOT_RECRUITING	A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome
NCT06840496	Phase 3	RECRUITING	To Investigate the Efficacy of Treatment With Oral NA-921 (Bionetide) Versus Placebo in Females With Rett Syndrome
NCT07480564	Phase 3	ACTIVE_NOT_RECRUITING	Safety and Preliminary Efficacy of TSHA-102 Gene Therapy in Pediatric Females Aged >2 to <4 Years With Rett Syndrome
NCT07503444	Phase 3	RECRUITING	A Phase 3 Study of Fenfluramine Hydrochloride in Rett Syndrome
NCT00593957	Phase 2	TERMINATED	Trial of Dextromethorphan in Rett Syndrome
NCT00990691	Phase 2	COMPLETED	Pilot Study of the Effects of the Desipramine on the Neurovegetative Parameters of the Child With Rett Syndrome
NCT01520363	Phase 2	COMPLETED	Placebo Controlled Trial of Dextromethorphan in Rett Syndrome
NCT01703533	Phase 2	COMPLETED	A Safety Study of NNZ-2566 in Patients With Rett Syndrome
NCT01777542	Phase 2	COMPLETED	Treatment of Rett Syndrome With Recombinant Human IGF-1
NCT01822249	Phase 2	COMPLETED	Phase 2 Study of EPI-743 for Treatment of Rett Syndrome
NCT02153723	Phase 2	COMPLETED	Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
NCT02563860	Phase 2	COMPLETED	Pharmacological Treatment of Rett Syndrome With Statins
NCT02696044	Phase 2	UNKNOWN	Treatment of Mitochondrial Dysfunction in Rett Syndrome With Triheptanoin
NCT02715115	Phase 2	COMPLETED	A Safety Study of NNZ-2566 in Pediatric Rett Syndrome
NCT03059160	Phase 2	UNKNOWN	Open Label Trial of Triheptanoin (UX007) in Treatment of Rett Syndrome.
NCT03633058	Phase 2	COMPLETED	A Study to Evaluate Ketamine for the Treatment of Rett Syndrome
NCT03758924	Phase 2	COMPLETED	Study of ANAVEX2-73 in Patients With Rett Syndrome
NCT04041713	Phase 2	RECRUITING	A Pilot Study of an Antioxidant Cocktail vs. Placebo in the Treatment of Children and Adolescents With Rett Syndrome
NCT05625568	Phase 2	UNKNOWN	Study of VYNT-0126 in the Treatment of Rett Syndrome in Adult Patients
NCT07640503	Phase 2	ENROLLING_BY_INVITATION	Lamivudine as a Novel Clinical Effort for Rett Syndrome
NCT01253317	Phase 1	COMPLETED	Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)
NCT02023424	Phase 1	UNKNOWN	An Open Label, Exploratory Study to Investigate the Treatment Effect of Glatiramer Acetate on Girls Woth Rett Syndrome
NCT02562820	Phase 1	TERMINATED	An Exploratory Trial of Ketamine for the Treatment of Rett Syndrome
NCT07150013	Phase 1	RECRUITING	Rett REVOLUTION Trial: An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Rett Syndrome
NCT02790034	Phase 2/3	TERMINATED	Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms
NCT04304482	Phase 2/3	COMPLETED	ANAVEX2-73 Study in Pediatric Patients With Rett Syndrome
NCT04988867	Phase 2/3	TERMINATED	An Open-Label Study of Trofinetide for the Treatment of Girls Two to Five Years of Age Who Have Rett Syndrome
NCT06849973	Phase 2/3	COMPLETED	To Study the Efficacy & Safety of Oral NA-921 (Bionetide) in Girls and Women with Rett Syndrome
NCT07257978	Phase 2/3	NOT_YET_RECRUITING	Efficacy and Safety of NTI164 in Children and Young Adults With Rett Syndrome
NCT06152237	Phase 1/2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of TSHA-102 in Pediatric Females With Rett Syndrome (REVEAL Pediatric Study)
NCT06621043	Phase 1/2	COMPLETED	Assessing the Safety and Efficacy of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) in the Treatment of Rett Syndrome (RTT)
NCT06199700	Early Phase 1	COMPLETED	Esketamine for the Treatment of Rett Syndrome
NCT06856759	Early Phase 1	ACTIVE_NOT_RECRUITING	Single-Dose AAV-MECP2 Safety/Tolerability and Efficacy in Rett Syndrome
NCT00004656	Not specified	COMPLETED	Nutritional Aspects of Rett Syndrome
NCT00004773	Not specified	COMPLETED	Study of Cardiac and Paroxysmal Abnormalities in Rett Syndrome
NCT00004807	Not specified	COMPLETED	Study of the Pathogenesis of Rett Syndrome
NCT00299312	Not specified	COMPLETED	Genetic and Physical Characteristics of Rett Syndrome
NCT00464477	Not specified	COMPLETED	Advanced Grandparental Age as a Risk Factor for Autism
NCT00630422	Not specified	COMPLETED	Functional Abilities in Rett Syndrome
NCT00786071	Not specified	COMPLETED	Metabolic Evaluation of Nutrition in Rett Syndrome
NCT00891956	Not specified	COMPLETED	The Role of Family Functioning in Adaptation to Being a Caregiver of an Individual With Rett Syndrome
NCT01147575	Not specified	COMPLETED	Effects of Creatine Supplementation in Rett Syndrome
NCT01198015	Not specified	COMPLETED	Creatine Metabolism in Rett Syndrome
NCT02360436	Not specified	WITHDRAWN	Analysis of the Glutathione Cycle in Children With Rett Syndrome
NCT02428673	Not specified	COMPLETED	Effects of Standing on Non-Ambulatory Children With Neuromuscular Conditions
NCT02670694	Not specified	COMPLETED	Sleep Abnormalities in Rare Genetic Disorders: AS, RTT, and PW
NCT02705677	Not specified	COMPLETED	Biobanking of Rett Syndrome and Related Disorders
NCT02738281	Not specified	COMPLETED	Natural History of Rett Syndrome & Related Disorders
NCT02885090	Not specified	COMPLETED	New Genes Involved in Molecular Etiology of Rett Syndrome Through DNA Microarray Comparative Genomic Hybridization
NCT02903056	Not specified	UNKNOWN	The Findings of MR Imaging in Rett Syndrome
NCT03175328	Not specified	UNKNOWN	CRRT Timing in Sepsis-associated AKI in ICU

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for METAP2 across ~30M SureChEMBL compounds — explore on Sugi Predict.