PCMT1

Summary

PCMT1 (protein-L-isoaspartate (D-aspartate) O-methyltransferase, HGNC:8728) is a protein-coding gene on chromosome 6q25.1, encoding Protein-L-isoaspartate(D-aspartate) O-methyltransferase (P22061). Initiates the repair of damaged proteins by catalyzing methyl esterification of L-isoaspartyl and D-aspartyl residues produced by spontaneous isomerization and racemization of L-aspartyl and L-asparaginyl residues in aging peptides and proteins.

This gene encodes a member of the type II class of protein carboxyl methyltransferase enzymes. The encoded enzyme plays a role in protein repair by recognizing and converting D-aspartyl and L-isoaspartyl residues resulting from spontaneous deamidation back to the normal L-aspartyl form. The encoded protein may play a protective role in the pathogenesis of Alzheimer’s disease, and single nucleotide polymorphisms in this gene have been associated with spina bifida and premature ovarian failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5110 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 37 total — 1 pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001360452

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8728
Approved symbol	PCMT1
Name	protein-L-isoaspartate (D-aspartate) O-methyltransferase
Location	6q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000120265
Ensembl biotype	protein_coding
OMIM	176851
Entrez	5110

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000367378, ENST00000367380, ENST00000367384, ENST00000460828, ENST00000464889, ENST00000480010, ENST00000484601, ENST00000486585, ENST00000494411, ENST00000495487, ENST00000544496, ENST00000863138, ENST00000863139, ENST00000863140, ENST00000863141, ENST00000863142, ENST00000917503, ENST00000917504, ENST00000917505, ENST00000917506, ENST00000917507, ENST00000941100, ENST00000941101, ENST00000941102, ENST00000941103

RefSeq mRNA: 8 — MANE Select: NM_001360452 NM_001252049, NM_001252050, NM_001252051, NM_001252052, NM_001252053, NM_001360452, NM_001360456, NM_005389

CCDS: CCDS59041, CCDS75533, CCDS75534, CCDS94017

Canonical transcript exons

ENST00000464889 — 8 exons

Exon	Start	End
ENSE00000813627	149796415	149796500
ENSE00000813630	149802200	149802416
ENSE00001938766	149749741	149749956
ENSE00003500046	149771162	149771266
ENSE00003511679	149793549	149793669
ENSE00003521363	149789954	149790058
ENSE00003683592	149773138	149773169
ENSE00003920640	149810616	149811419

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 70.4765 / max 549.2969, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70496	68.5222	1827
70495	1.9542	1252

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.73	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.57	gold quality
middle temporal gyrus	UBERON:0002771	99.41	gold quality
pons	UBERON:0000988	99.38	gold quality
frontal pole	UBERON:0002795	99.18	gold quality
dorsal root ganglion	UBERON:0000044	99.04	gold quality
prefrontal cortex	UBERON:0000451	98.86	gold quality
orbitofrontal cortex	UBERON:0004167	98.83	gold quality
trigeminal ganglion	UBERON:0001675	98.68	gold quality
substantia nigra pars compacta	UBERON:0001965	98.67	gold quality
superior vestibular nucleus	UBERON:0007227	98.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.62	gold quality
primary visual cortex	UBERON:0002436	98.61	gold quality
heart right ventricle	UBERON:0002080	98.57	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.56	gold quality
occipital lobe	UBERON:0002021	98.54	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.53	gold quality
oocyte	CL:0000023	98.51	gold quality
biceps brachii	UBERON:0001507	98.50	gold quality
superior frontal gyrus	UBERON:0002661	98.49	gold quality
frontal cortex	UBERON:0001870	98.43	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.32	gold quality
neocortex	UBERON:0001950	98.30	gold quality
secondary oocyte	CL:0000655	98.28	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.27	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.25	gold quality
cerebral cortex	UBERON:0000956	98.22	gold quality
entorhinal cortex	UBERON:0002728	98.18	gold quality
gastrocnemius	UBERON:0001388	98.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting PCMT1, 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-223-3P	99.99	70.14	1140
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-589-3P	99.91	69.62	2088

Literature-anchored findings (GeneRIF, showing 36)

• Protein L-Isoaspartyl Methyltransferase (PMID:11792715)
• crystal structure complexed with adenosyl homocysteine (AdoHcy) to 1.6-A resolution (PMID:11847284)
• Our results showed that the Ile120Val polymorphism of PCMT1 gene is a genetic modifier for the risk of spina bifida. Val/Val genotype was associated with a reduction in risk for spina bifida. (PMID:16256389)
• A potential role for PIMT in biological processes such as wound healing, cell migration, and tumor metastasis dissemination. (PMID:17167531)
• These results suggest that PIMT repair of abnormal proteins is necessary to maintain normal MAPK signaling. (PMID:18381200)
• Four polymorphisms in the protein L-isoaspartyl-O-methyltransferase (PCMT1) gene, encoding a protein repair enzyme, are associated with premature ovarian failure (POF). (PMID:18582870)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• study demonstrates a novel role for PIMT as a negative regulator of Abeta peptide formation and a potential protective factor in the pathogenesis of Alzheimer disease (PMID:21372823)
• Data show six differentially expressed proteins were identified as HSP70, PPIA and alpha-Enolase (up-regulated) S100-A9, PIMT and beta-5 tubulin (down-regulated), most of which had been shown to play a potential role in the pathogenesis of atherosclerosis. (PMID:21839816)
• A tight cross-regulation exists between ERK and PIMT in regards to their activation and expression during the epithelial mesenchymal transition. (PMID:21841813)
• PIMT may act as a co-activator in ERalpha-mediated transcription of TFF1 through its recruitment to the promoter via interacting with ERalpha. (PMID:22382029)
• The results implied that maternal polymorphisms in PCMT1 might be a potential genetic risk factor for isolated anencephaly in the Chinese population of Lvliang. (PMID:22647835)
• Study provides new insight into the molecular mechanisms by which PIMT suppresses the p53 activity through carboxyl methylation, and suggests a therapeutic target for cancers. (PMID:22735455)
• Overexpression of PCMT1 attentuates Mst1 kinase activation and its apoptotic effects in response to hypoxia-induced injury in cardiomyocytes. (PMID:23647599)
• Data indicate that human PROTEIN ISOASPARTYL METHYLTRANSFERASE (PIMT) can initiate isoAsp conversion to Asp, and is able to restore Arabidopsis PRH75’s complex biochemical activity provided isoAsp formation has not led to conformational alterations. (PMID:23903319)
• ERK2-mediated phosphorylation of transcriptional coactivator binding protein PIMT/NCoA6IP at Ser298 augments hepatic gluconeogenesis. (PMID:24358311)
• The data of this study indicated that DA-associated PIMT downregulation is an important event contributing to neuronal cell death (PMID:25800307)
• Strong PIMT expression was a predictive marker of poor prognosis for surgically resected lung adenocarcinoma. (PMID:26997432)
• decrease of PCMT1 significantly increased the proportion of D-Asp residues in PHB1 and had significant and fatal impacts on morphology and functions of the mitochondria, such as ATP production and the mitochondrial fusion-fission system (PMID:27327778)
• PIMT heterozygosity for R36C, G175R, R17H, or R17S would be detrimental to successful aging, whereas homozygosity (should it ever occur) would produce devastating neuropathology (PMID:28100787)
• High expression of PCMT1 is associated with pancreatic cancer. (PMID:29517839)
• The new findings reported here extend the list of human PIMT variants that may contribute to neurological diseases in the young and the decline of CNS function in the aged. (PMID:29856810)
• PIMT Binding to C-Terminal Ala459 of CAIX Is Involved in Inside-Out Signaling Necessary for Its Catalytic Activity. (PMID:33198416)
• The enzyme L-isoaspartyl (D-aspartyl) methyltransferase promotes migration and invasion in human U-87 MG and U-251 MG glioblastoma cell lines. (PMID:34082401)
• Genome-wide CRISPR/Cas9 library screen identifies PCMT1 as a critical driver of ovarian cancer metastasis. (PMID:35033172)
• PIMT/TGS1: An evolving metabolic molecular switch with conserved methyl transferase activity. (PMID:35462043)
• PCMT1 Is a Potential Prognostic Biomarker and Is Correlated with Immune Infiltrates in Breast Cancer. (PMID:35535040)
• The Protein L-Isoaspartyl (D-Aspartyl) Methyltransferase Regulates Glial-to-Mesenchymal Transition and Migration Induced by TGF-beta1 in Human U-87 MG Glioma Cells. (PMID:35628507)
• In vitro Anti-malignant Property of PCMT1 Silencing and Identification of the SNHG16/miR-195/PCMT1 Regulatory Axis in Breast Cancer Cells. (PMID:36639265)
• The role of PIMT in Alzheimer’s disease pathogenesis: A novel hypothesis. (PMID:37157118)
• The Role of Protein-L-isoaspartyl Methyltransferase (PIMT) in the Suppression of Toxicity of the Oligomeric Form of Abeta42, in Addition to the Inhibition of Its Fibrillization. (PMID:37535852)
• PCMT1 is a potential target related to tumor progression and immune infiltration in liver cancer. (PMID:37596654)
• PCMT1 regulates the migration, invasion, and apoptosis of prostate cancer through modulating the PI3K/AKT/GSK-3beta pathway. (PMID:37899170)
• PCMT1 knockdown attenuates malignant properties by globally regulating transcriptome profiles in triple-negative breast cancer cells. (PMID:37953789)
• [Prognostic Value of PCMT1 Expression in Gastric Cancer and Its Regulatory Effect on Spindle Assembly Checkpoints]. (PMID:38162070)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcmt	ENSDARG00000015201
mus_musculus	Pcmt1	ENSMUSG00000019795
rattus_norvegicus	Pcmt1	ENSRNOG00000014330
drosophila_melanogaster	Pcmt	FBGN0086768
caenorhabditis_elegans		WBGENE00003954

Paralogs (2): PCMTD1 (ENSG00000168300), PCMTD2 (ENSG00000203880)

Protein

Protein identifiers

Protein-L-isoaspartate(D-aspartate) O-methyltransferase — P22061 (reviewed: P22061)

Alternative names: L-isoaspartyl protein carboxyl methyltransferase, Protein L-isoaspartyl/D-aspartyl methyltransferase, Protein-beta-aspartate methyltransferase

All UniProt accessions (9): A0A384MDK7, A0A3F2YNX8, C9J0F2, P22061, F6S8N6, F8WAV5, F8WAX2, F8WDT3, H7C4X2

UniProt curated annotations — full annotation on UniProt →

Function. Initiates the repair of damaged proteins by catalyzing methyl esterification of L-isoaspartyl and D-aspartyl residues produced by spontaneous isomerization and racemization of L-aspartyl and L-asparaginyl residues in aging peptides and proteins. Acts on EIF4EBP2, microtubule-associated protein 2, calreticulin, clathrin light chains a and b, Ubiquitin C-terminal hydrolase isozyme L1, phosphatidylethanolamine-binding protein 1, stathmin, beta-synuclein and alpha-synuclein.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol.

Polymorphism. The allele frequencies for the polymorphism at codon 120 differ between ethnic groups; in the Caucasian population Ile-120 is present at a frequency of 0.45, while it is found at a frequency of 0.88 and 0.81 in the Asian and the African populations respectively. Val-120 is found at a frequency of 0.55 in the Caucasians, 0.12 and 0.19 in the Asian and African populations respectively. The Ile-120 variant has higher specific activity and thermostability than the Val-120 variant. The Val-120 variant has a higher affinity for protein substrates.

Similarity. Belongs to the methyltransferase superfamily. L-isoaspartyl/D-aspartyl protein methyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P22061-1	1	yes
P22061-2	2

RefSeq proteins (8): NP_001238978, NP_001238979, NP_001238980, NP_001238981, NP_001238982, NP_001347381, NP_001347385, NP_005380 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000682	PCMT	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily

Pfam: PF01135

Enzyme classification (BRENDA):

• EC 2.1.1.77 — protein-L-isoaspartate(D-aspartate) O-methyltransferase (BRENDA: 45 organisms, 176 substrates, 11 inhibitors, 135 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
S-ADENOSYL-L-METHIONINE	0.0009–0.03	19
OVALBUMIN	0.0046–12.7	18
VYP-L-ISOASP-HA	0.0003–0.38	12
KASA (ISOASP) LAKY	0.0003–0.0506	8
KASA (ISOD) LAKY	0.0004–0.0506	8
VYP (ISOD) HA	0.0003–0.0336	6
KASA(ISO-D)LAKY	0.0145–0.0286	3
N-SUCCINYL-AAVAP-NITROANILIDE	0.375–11	3
OVALBUMIN L-ISOASPARTATE	0.0423–0.159	3
VYP (ISOASP) HA	0.0003–0.0118	3
VYP-(L-ISO-ASP)-HA	0.133–0.153	3
KASA (D-ASP) LAKY	0.023–2.7	2
KASA-ISOD-LAKY	0.008–0.12	2
KASA-L-ISOASP-LAKY	0.08–0.092	2
VAL-TYR-PRO(L-ISO-ASPARTATE)-HIS-ALA	0.208–0.27	2

Catalyzed reactions (Rhea), 1 shown:

• [protein]-L-isoaspartate + S-adenosyl-L-methionine = [protein]-L-isoaspartate alpha-methyl ester + S-adenosyl-L-homocysteine (RHEA:12705)

UniProt features (43 total): helix 11, strand 11, binding site 7, sequence conflict 6, turn 2, initiator methionine 1, chain 1, modified residue 1, splice variant 1, sequence variant 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1I1N	X-RAY DIFFRACTION	1.5
1KR5	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22061-F1	96.10	0.94

Functional residue map

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

Catalytic / active sites (1): 60

Ligand- & substrate-binding residues (7): 57–60; 65; 89; 110–111; 142–143; 217; 222

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5676934	Protein repair

MSigDB gene sets: 196 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, DORSAM_HOXA9_TARGETS_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MORF_UBE2I, MORF_HDAC1, MORF_CDK2, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, chr6q25, ONKEN_UVEAL_MELANOMA_UP, MORF_CTBP1, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GROSS_HYPOXIA_VIA_ELK3_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN

GO Biological Process (4): protein methylation (GO:0006479), protein repair (GO:0030091), methylation (GO:0032259), protein modification process (GO:0036211)

GO Molecular Function (5): protein-L-isoaspartate (D-aspartate) O-methyltransferase activity (GO:0004719), cadherin binding (GO:0045296), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062), extracellular vesicle (GO:1903561)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
cellular anatomical structure	2
protein alkylation	1
macromolecule methylation	1
metabolic process	1
macromolecule modification	1
S-adenosylmethionine-dependent methyltransferase activity	1
protein carboxyl O-methyltransferase activity	1
cell adhesion molecule binding	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1
extracellular region	1
vesicle	1
extracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCMT1	ICMT	O60725	605
PCMT1	KATNA1	O75449	510
PCMT1	ALDH16A1	Q8IZ83	502
PCMT1	TIA1	P31483	501
PCMT1	PPP1R14C	Q8TAE6	485
PCMT1	TTC7B	Q86TV6	435
PCMT1	ZC3H15	Q8WU90	435
PCMT1	TDP2	O95551	433
PCMT1	MRPL15	Q9P015	427
PCMT1	BORCS5	Q969J3	425
PCMT1	HSPA8	P11142	423
PCMT1	PPIL4	Q8WUA2	419
PCMT1	C19orf25	Q9UFG5	418
PCMT1	ZNF398	Q8TD17	418
PCMT1	GART	P22102	417

IntAct

154 interactions, top by confidence:

A	B	Type	Score
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PCMT1	RPIA	psi-mi:“MI:0915”(physical association)	0.670
RPIA	PCMT1	psi-mi:“MI:0915”(physical association)	0.670
AIMP2	PCMT1	psi-mi:“MI:0915”(physical association)	0.560
PCMT1	AIMP2	psi-mi:“MI:0915”(physical association)	0.560
rep	PCMT1	psi-mi:“MI:0915”(physical association)	0.560
rep	PCMT1	psi-mi:“MI:0914”(association)	0.560
CSNK1E	POTEF	psi-mi:“MI:0914”(association)	0.530
COPS7B	ZZEF1	psi-mi:“MI:0914”(association)	0.530
P/V	HSPA4L	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
EN1	NFIB	psi-mi:“MI:2364”(proximity)	0.470
TNFAIP3	LRRIQ3	psi-mi:“MI:0914”(association)	0.420
TNFAIP3	LRRIQ3	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (368): PCMT1 (Affinity Capture-MS), AIMP2 (Two-hybrid), RPIA (Two-hybrid), PCMT1 (Affinity Capture-MS), PCMT1 (Affinity Capture-MS), PCMT1 (Affinity Capture-MS), ALDH16A1 (Affinity Capture-MS), TMEM102 (Affinity Capture-MS), DERA (Affinity Capture-MS), PDPR (Affinity Capture-MS), DTYMK (Affinity Capture-MS), RAB3IP (Affinity Capture-MS), C18orf8 (Affinity Capture-MS), RPIA (Affinity Capture-MS), CSNK1E (Affinity Capture-MS)

ESM2 similar proteins: A5A6K8, A5A6N7, B4G0F3, O35678, O75608, O77821, P00341, P07687, P15246, P16125, P17174, P22061, P22062, P33571, P42123, P70470, P79381, P80895, P97823, Q0V9A9, Q3MHR0, Q3UFF7, Q42539, Q42563, Q4I8Q4, Q4R5H0, Q53H82, Q5RA89, Q5RBR7, Q5RBU3, Q5XGR8, Q6AV34, Q6P7K0, Q7TP52, Q7TSV4, Q84WK4, Q8GWU0, Q8GYK2, Q8R1G2, Q92047

Diamond homologs: A0B9U1, A0LM89, A1ASW6, A1K4F0, A1RSC6, A1U4P7, A1V4L2, A2BKH8, A2S291, A2SF76, A3CXP8, A3DMG3, A3MK86, A3MY16, A3NA64, A3NVY1, A4G087, A4WNC5, A5CYQ6, A5G4S7, A5W820, A6LNM3, A6UR90, A6UWM1, A6V1G4, A6VI91, A6X6Y1, A7HC32, A7HL14, A7HXK6, A8AAV7, A9A8I9, A9BH07, A9IP04, B0KSC8, B1JB29, B1L6T9, B1YC47, B1ZPF0, B3E6I4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
638121	GRCh37/hg19 6q24.3-25.1(chr6:148690764-150494873)x1	Pathogenic

SpliceAI

1585 predictions. Top by Δscore:

Variant	Effect	Δscore
6:149749954:GCA:G	donor_gain	1.0000
6:149749957:G:GG	donor_gain	1.0000
6:149771135:T:TA	acceptor_gain	1.0000
6:149771151:A:AG	acceptor_gain	1.0000
6:149771151:ACTT:A	acceptor_gain	1.0000
6:149771152:C:G	acceptor_gain	1.0000
6:149771154:T:A	acceptor_gain	1.0000
6:149771157:TTCAG:T	acceptor_loss	1.0000
6:149771160:A:AG	acceptor_gain	1.0000
6:149771160:A:AT	acceptor_loss	1.0000
6:149771161:G:GT	acceptor_gain	1.0000
6:149771161:G:T	acceptor_loss	1.0000
6:149771161:GA:G	acceptor_gain	1.0000
6:149771161:GAA:G	acceptor_gain	1.0000
6:149771161:GAAA:G	acceptor_gain	1.0000
6:149771161:GAAAA:G	acceptor_gain	1.0000
6:149771263:ATAG:A	donor_gain	1.0000
6:149771264:TAG:T	donor_gain	1.0000
6:149771265:AG:A	donor_gain	1.0000
6:149771265:AGGT:A	donor_loss	1.0000
6:149771266:GG:G	donor_gain	1.0000
6:149771266:GGT:G	donor_loss	1.0000
6:149771267:G:GG	donor_gain	1.0000
6:149771268:T:A	donor_loss	1.0000
6:149773134:GCAG:G	acceptor_loss	1.0000
6:149773135:CA:C	acceptor_loss	1.0000
6:149773136:A:AG	acceptor_gain	1.0000
6:149773137:G:GA	acceptor_gain	1.0000
6:149773170:G:GG	donor_gain	1.0000
6:149773175:T:G	donor_gain	1.0000

AlphaMissense

1481 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:149749951:T:C	L17P	1.000
6:149771248:G:C	D48H	1.000
6:149773155:A:C	S60R	1.000
6:149773157:T:A	S60R	1.000
6:149773157:T:G	S60R	1.000
6:149773159:C:A	A61D	1.000
6:149790030:G:A	G90E	1.000
6:149749939:T:C	L13P	0.999
6:149771215:C:A	R37S	0.999
6:149771249:A:C	D48A	0.999
6:149771249:A:T	D48V	0.999
6:149771255:C:A	P50Q	0.999
6:149773156:G:A	S60N	0.999
6:149773162:C:A	P62Q	0.999
6:149773164:C:G	H63D	0.999
6:149790009:T:A	L83H	0.999
6:149790009:T:C	L83P	0.999
6:149790017:G:A	G86R	0.999
6:149790017:G:C	G86R	0.999
6:149790018:G:A	G86E	0.999
6:149790024:G:A	G88E	0.999
6:149790024:G:T	G88V	0.999
6:149790030:G:T	G90V	0.999
6:149793574:G:A	G108E	0.999
6:149793595:T:C	L115P	0.999
6:149796432:G:A	G146R	0.999
6:149796432:G:C	G146R	0.999
6:149796463:T:A	I156N	0.999
6:149796465:C:G	H157D	0.999
6:149796471:G:A	G159R	0.999

dbSNP variants (sampled 300 via entrez): RS1000015020 (6:149758096 A>C,T), RS1000080890 (6:149804680 T>A), RS1000097864 (6:149756742 T>G), RS1000118515 (6:149751423 C>T), RS1000191618 (6:149751682 A>C,G), RS1000198344 (6:149791552 G>A), RS1000220628 (6:149772702 G>A), RS1000223337 (6:149798044 C>G,T), RS1000237866 (6:149791129 T>C,G), RS1000270832 (6:149747825 A>G,T), RS1000271246 (6:149809859 A>C,G), RS1000290183 (6:149791502 C>A), RS1000448708 (6:149753639 TTTTTGTTTTG>T,TTTTTG,TTTTTGTTTTGTTTTG), RS1000459552 (6:149767689 A>G), RS1000492765 (6:149758451 C>A)

Disease associations

OMIM: gene MIM:176851 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010702_29	Subcortical volume (MOSTest)	7.000000e-11
GCST010703_317	Brain morphology (MOSTest)	7.000000e-22
GCST012020_567	Serum metabolite levels	1.000000e-20
GCST012021_15	Serum metabolite levels	1.000000e-20

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4240 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 5,225 (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
CHEMBL1088977	ADEMETIONINE	3	1,522
CHEMBL1214186	SINEFUNGIN	2	2,165
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 8 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.41	Kd	392.7	nM	CHEMBL5653589
6.41	ED50	392.7	nM	CHEMBL5653589
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 18 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148947: Binding affinity to human PCMT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.3927	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179059: Inhibition of PCMT1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects expression	4
bisphenol A	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Rotenone	decreases expression, increases expression	2
Aflatoxin B1	increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Okadaic Acid	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
1,3-dimethylthiourea	decreases expression, decreases reaction	1
beta-methylcholine	affects expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
azoxystrobin	increases expression	1
chloropicrin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651989	Binding	Binding affinity to human PCMT1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1PK	Abcam K-562 PCMT1 KO	Cancer cell line	Female
CVCL_D2L6	Abcam Raji PCMT1 KO	Cancer cell line	Male
CVCL_TC53	HAP1 PCMT1 (-) 1	Cancer cell line	Male
CVCL_TC54	HAP1 PCMT1 (-) 2	Cancer cell line	Male
CVCL_WQ21	Abcam Jurkat PCMT1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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