PCMTD2

Summary

PCMTD2 (protein-L-isoaspartate (D-aspartate) O-methyltransferase domain containing 2, HGNC:15882) is a protein-coding gene on chromosome 20q13.33, encoding Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (Q9NV79). May act as a substrate recognition component of an ECS (Elongin BC-CUL5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

Predicted to enable protein-L-isoaspartate (D-aspartate) O-methyltransferase activity. Predicted to be involved in protein modification process. Predicted to be active in cytoplasm.

Source: NCBI Gene 55251 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 42 total — 1 pathogenic
• MANE Select transcript: NM_018257

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15882
Approved symbol	PCMTD2
Name	protein-L-isoaspartate (D-aspartate) O-methyltransferase domain containing 2
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10883
Ensembl gene	ENSG00000203880
Ensembl biotype	protein_coding
OMIM	620077
Entrez	55251

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 36 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000266078, ENST00000299468, ENST00000308824, ENST00000369758, ENST00000608844, ENST00000609297, ENST00000609372, ENST00000609764, ENST00000609818, ENST00000610074, ENST00000610196, ENST00000901805, ENST00000901806, ENST00000901807, ENST00000901808, ENST00000901809, ENST00000901810, ENST00000901811, ENST00000901812, ENST00000901813, ENST00000901814, ENST00000901815, ENST00000912347, ENST00000912348, ENST00000912349, ENST00000912350, ENST00000912351, ENST00000912352, ENST00000912353, ENST00000912354, ENST00000912355, ENST00000912356, ENST00000912357, ENST00000912358, ENST00000912359, ENST00000912360, ENST00000943735, ENST00000943736, ENST00000943737, ENST00000943738

RefSeq mRNA: 2 — MANE Select: NM_018257 NM_001104925, NM_018257

CCDS: CCDS13559, CCDS46631

Canonical transcript exons

ENST00000308824 — 6 exons

Exon	Start	End
ENSE00000663673	64264429	64264531
ENSE00000663675	64267887	64268010
ENSE00000856691	64259942	64260272
ENSE00001329119	64265258	64265429
ENSE00001821274	64273221	64276226
ENSE00001902652	64255748	64255870

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.0570 / max 306.1738, expressed in 1775 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185949	16.0014	1757
185950	3.9763	1265
185948	0.6698	414
185951	0.2249	78
209209	0.1848	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	98.98	gold quality
retina	UBERON:0000966	98.95	gold quality
upper leg skin	UBERON:0004262	97.06	gold quality
gall bladder	UBERON:0002110	96.83	gold quality
ganglionic eminence	UBERON:0004023	96.68	gold quality
left ovary	UBERON:0002119	96.54	gold quality
cortical plate	UBERON:0005343	96.45	gold quality
cerebellar hemisphere	UBERON:0002245	96.38	gold quality
cerebellar cortex	UBERON:0002129	96.31	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.30	gold quality
sural nerve	UBERON:0015488	96.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.24	gold quality
skin of hip	UBERON:0001554	96.23	gold quality
ovary	UBERON:0000992	96.10	gold quality
right ovary	UBERON:0002118	95.91	gold quality
ventricular zone	UBERON:0003053	95.73	gold quality
lymph node	UBERON:0000029	95.51	gold quality
right uterine tube	UBERON:0001302	95.45	gold quality
cerebellum	UBERON:0002037	95.35	gold quality
embryo	UBERON:0000922	95.29	gold quality
body of pancreas	UBERON:0001150	95.03	gold quality
cardiac atrium	UBERON:0002081	95.03	gold quality
endocervix	UBERON:0000458	94.99	gold quality
heart right ventricle	UBERON:0002080	94.91	gold quality
right atrium auricular region	UBERON:0006631	94.91	gold quality
choroid plexus epithelium	UBERON:0003911	94.90	gold quality
body of uterus	UBERON:0009853	94.89	gold quality
adrenal tissue	UBERON:0018303	94.87	gold quality
skin of abdomen	UBERON:0001416	94.68	gold quality
corpus epididymis	UBERON:0004359	94.64	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)

128 targeting PCMTD2, 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-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-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcmtd2a	ENSDARG00000053820
danio_rerio	PCMTD2	ENSDARG00000104883
mus_musculus	Pcmtd2	ENSMUSG00000027589
rattus_norvegicus	Pcmtd2	ENSRNOG00000017404
caenorhabditis_elegans	R119.5	WBGENE00020090

Paralogs (2): PCMT1 (ENSG00000120265), PCMTD1 (ENSG00000168300)

Protein

Protein identifiers

Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 — Q9NV79 (reviewed: Q9NV79)

All UniProt accessions (7): Q9NV79, F8W9F3, V9GYG6, V9GYL1, V9GYZ4, V9GYZ7, V9GZ41

UniProt curated annotations — full annotation on UniProt →

Function. May act as a substrate recognition component of an ECS (Elongin BC-CUL5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. May bind to the methyltransferase cofactor S-adenosylmethionine (AdoMet) via the N-terminal AdoMet binding motif, but probably does not display methyltransferase activity.

Subcellular location. Cytoplasm.

Domain organisation. At its N-terminus, contains L-isoaspartate and S-adenosylmethionine (AdoMet) binding motifs. Also contains an extended SOCS box motif, where the Cul-box is separated from the BC-box by ~90 residues, within its C-terminus.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NV79-1	1	yes
Q9NV79-2	2
Q9NV79-3	3

RefSeq proteins (2): NP_001098395, NP_060727* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000682	PCMT	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily

Pfam: PF01135

UniProt features (16 total): region of interest 6, splice variant 3, compositionally biased region 2, initiator methionine 1, chain 1, active site 1, lipid moiety-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NV79-F1	82.51	0.71

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): 64

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 151 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DOUGLAS_BMI1_TARGETS_DN, ZHANG_BREAST_CANCER_PROGENITORS_UP, CUI_TCF21_TARGETS_2_DN, RODRIGUES_DCC_TARGETS_DN, NUYTTEN_EZH2_TARGETS_DN, LAIHO_COLORECTAL_CANCER_SERRATED_DN, ZHENG_GLIOBLASTOMA_PLASTICITY_DN, GOMF_O_METHYLTRANSFERASE_ACTIVITY, GOMF_PROTEIN_METHYLTRANSFERASE_ACTIVITY, GOMF_S_ADENOSYLMETHIONINE_DEPENDENT_METHYLTRANSFERASE_ACTIVITY, NIKOLSKY_BREAST_CANCER_20Q12_Q13_AMPLICON, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN

GO Biological Process (1): protein modification process (GO:0036211)

GO Molecular Function (2): protein-L-isoaspartate (D-aspartate) O-methyltransferase activity (GO:0004719), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
macromolecule modification	1
S-adenosylmethionine-dependent methyltransferase activity	1
protein carboxyl O-methyltransferase activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCMTD2	PRPSAP1	Q14558	541
PCMTD2	CHST10	O43529	498
PCMTD2	PRDM13	Q9H4Q3	474
PCMTD2	ANKRD16	Q6P6B7	471
PCMTD2	ZNF337	Q9Y3M9	470
PCMTD2	VWC2L	B2RUY7	462
PCMTD2	EEF1AKMT1	Q8WVE0	461
PCMTD2	RAB11FIP5	Q9BXF6	459
PCMTD2	NFKBIL1	Q9UBC1	458
PCMTD2	EARS2	Q5JPH6	446
PCMTD2	SLC2A6	Q9UGQ3	445
PCMTD2	ASB12	Q8WXK4	435
PCMTD2	GNAI1	P04898	433
PCMTD2	SNRNP48	Q6IEG0	422
PCMTD2	TLX3	O43711	420

IntAct

70 interactions, top by confidence:

A	B	Type	Score
CUL5	SOCS2	psi-mi:“MI:0914”(association)	0.880
CUL5	SOCS6	psi-mi:“MI:0914”(association)	0.640
CUL5	SOCS7	psi-mi:“MI:0914”(association)	0.640
PCMTD2	ACSL6	psi-mi:“MI:0915”(physical association)	0.560
PCMTD2	DCTN1	psi-mi:“MI:0915”(physical association)	0.560
PCMTD2	DMWD	psi-mi:“MI:0915”(physical association)	0.560
PCMTD2		psi-mi:“MI:0915”(physical association)	0.560
NOS3	PCMTD2	psi-mi:“MI:0915”(physical association)	0.560
PRKN	PCMTD2	psi-mi:“MI:0915”(physical association)	0.560
PCMTD2	PMP22	psi-mi:“MI:0915”(physical association)	0.560
VHL	PCMTD2	psi-mi:“MI:0915”(physical association)	0.560
PCMTD2	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
PCMTD2	RNF11	psi-mi:“MI:0915”(physical association)	0.560
PCMTD2	HTRA2	psi-mi:“MI:0915”(physical association)	0.560
PCMTD2	JPH3	psi-mi:“MI:0915”(physical association)	0.560
PCMTD2	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
SNCA	PCMTD2	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	PCMTD2	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	PCMTD2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (40): PCMTD2 (Two-hybrid), VAC14 (Two-hybrid), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Affinity Capture-MS), PCMTD2 (Two-hybrid)

ESM2 similar proteins: A2VDP2, A3KMI0, B2RR83, B4NBB0, D3ZA12, F8VPZ3, O43314, O60678, P19838, P25799, P41229, P41230, P51186, P59913, Q04861, Q10003, Q14BI7, Q17902, Q1LXK4, Q1LXK5, Q29RZ2, Q38JA7, Q3MHU3, Q58CZ2, Q5NVL7, Q5R746, Q5R7E5, Q5R7K4, Q5REW0, Q5ZMR3, Q62240, Q63369, Q6BX78, Q6F3J0, Q6IQX0, Q6J5K9, Q7K175, Q7Z478, Q80Y84, Q8BHD8

Diamond homologs: A2VDP2, A7HHV3, P59913, Q11TS0, Q58CZ2, Q5R7E5, Q5R7K4, Q5ZMR3, Q8BHD8, Q96MG8, Q9NV79, A8AAV7, B1L6T9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neddylation	6	10.9×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	6	9.8×	2e-03
protein ubiquitination	7	9.1×	2e-03
positive regulation of apoptotic process	5	8.9×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564634	GRCh37/hg19 20q13.33(chr20:62090403-62915555)x1	Pathogenic

SpliceAI

1499 predictions. Top by Δscore:

Variant	Effect	Δscore
20:64255868:G:GT	donor_gain	1.0000
20:64264527:GACAA:G	donor_gain	1.0000
20:64264532:G:GG	donor_gain	1.0000
20:64265288:T:A	acceptor_gain	1.0000
20:64265289:G:A	acceptor_gain	1.0000
20:64265428:AG:A	donor_loss	1.0000
20:64265429:GG:G	donor_loss	1.0000
20:64265430:G:A	donor_loss	1.0000
20:64265431:T:A	donor_loss	1.0000
20:64273213:T:TA	acceptor_gain	1.0000
20:64273219:A:AG	acceptor_gain	1.0000
20:64273220:G:GG	acceptor_gain	1.0000
20:64259941:GT:G	acceptor_gain	0.9900
20:64259941:GTATT:G	acceptor_gain	0.9900
20:64264423:TTTTA:T	acceptor_loss	0.9900
20:64264424:TTTAG:T	acceptor_loss	0.9900
20:64264426:TA:T	acceptor_loss	0.9900
20:64264427:A:AG	acceptor_gain	0.9900
20:64264427:A:AT	acceptor_loss	0.9900
20:64264428:G:GG	acceptor_gain	0.9900
20:64264519:A:AG	donor_gain	0.9900
20:64264532:G:GA	donor_loss	0.9900
20:64264534:A:AG	donor_loss	0.9900
20:64265254:CCA:C	acceptor_loss	0.9900
20:64265257:G:A	acceptor_loss	0.9900
20:64265286:ACT:A	acceptor_gain	0.9900
20:64265286:ACTG:A	acceptor_gain	0.9900
20:64265421:G:GT	donor_gain	0.9900
20:64265426:GAAG:G	donor_gain	0.9900
20:64267879:T:TA	acceptor_gain	0.9900

AlphaMissense

2365 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:64259969:G:C	G2R	1.000
20:64259969:G:T	G2C	1.000
20:64259981:A:C	S6R	1.000
20:64259983:T:A	S6R	1.000
20:64259983:T:G	S6R	1.000
20:64259987:G:C	G8R	1.000
20:64259988:G:A	G8D	1.000
20:64260006:T:C	L14P	1.000
20:64260018:T:C	L18S	1.000
20:64260018:T:G	L18W	1.000
20:64260036:T:A	I24N	1.000
20:64260066:G:C	R34T	1.000
20:64260067:A:C	R34S	1.000
20:64260067:A:T	R34S	1.000
20:64260077:C:A	R38S	1.000
20:64260114:C:A	A50D	1.000
20:64260116:T:G	Y51D	1.000
20:64260122:G:C	D53H	1.000
20:64260122:G:T	D53Y	1.000
20:64260123:A:C	D53A	1.000
20:64260123:A:G	D53G	1.000
20:64260123:A:T	D53V	1.000
20:64260124:C:A	D53E	1.000
20:64260124:C:G	D53E	1.000
20:64260129:C:A	A55E	1.000
20:64260129:C:T	A55V	1.000
20:64260131:T:A	W56R	1.000
20:64260131:T:C	W56R	1.000
20:64260149:C:G	H62D	1.000
20:64260150:A:G	H62R	1.000

dbSNP variants (sampled 300 via entrez): RS1000131539 (20:64259288 A>G), RS1000250389 (20:64275419 T>C), RS1000374213 (20:64263685 G>C), RS1000382586 (20:64253933 G>A), RS1000400020 (20:64263439 G>A), RS1000693029 (20:64269580 G>A), RS1001036599 (20:64263403 G>A), RS1001201269 (20:64269025 C>T), RS1001265082 (20:64258890 T>A), RS1001333214 (20:64257225 C>T), RS1001911701 (20:64269299 C>T), RS1002103549 (20:64273797 G>T), RS1002267552 (20:64257514 G>T), RS1002448673 (20:64262840 G>A), RS1002559072 (20:64274052 G>A)

Disease associations

OMIM: gene MIM:620077 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002777_1	Clozapine-induced cytotoxicity	8.000000e-07
GCST008059_234	Estimated glomerular filtration rate	3.000000e-10
GCST008521_24	Bitter beverage consumption	2.000000e-08
GCST008524_5	Bitter non-alcoholic beverage consumption	5.000000e-09
GCST008526_42	Coffee consumption	2.000000e-11
GCST010243_102	Apolipoprotein B levels	7.000000e-13
GCST010245_68	LDL cholesterol levels	3.000000e-11
GCST011124_10	Caffeine consumption from tea	2.000000e-12
GCST011126_35	Caffeine consumption from coffee or tea	5.000000e-22
GCST011126_9	Caffeine consumption from coffee or tea	2.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement
EFO:0010089	bitter beverage consumption measurement
EFO:0010093	bitter non-alcoholic beverage consumption measurement
EFO:0006781	coffee consumption measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
Valproic Acid	affects expression, decreases expression, increases methylation	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Silicon Dioxide	decreases expression	2
Cyclosporine	decreases expression	2
afuresertib	increases expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
abrine	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Arbutin	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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