PYM1

gene
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Also known as PYM

Summary

PYM1 (PYM1 exon junction complex associated factor, HGNC:30258) is a protein-coding gene on chromosome 12q13.2, encoding Partner of Y14 and mago (Q9BRP8). Key regulator of the exon junction complex (EJC), a multiprotein complex that associates immediately upstream of the exon-exon junction on mRNAs and serves as a positional landmark for the intron exon structure of genes and directs post-transcriptional processes in the cytoplasm…. It is a selective cancer dependency (DepMap: 29.7% of cell lines).

Enables ribosome binding activity. Involved in exon-exon junction complex disassembly; nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; and positive regulation of translation. Located in cell junction; cytosol; and nuclear lumen. Part of exon-exon junction complex.

Source: NCBI Gene 84305 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 11 total
  • Druggable target: yes
  • Cancer dependency (DepMap): dependent in 29.7% of screened cell lines
  • MANE Select transcript: NM_032345

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:30258
Approved symbolPYM1
NamePYM1 exon junction complex associated factor
Location12q13.2
Locus typegene with protein product
StatusApproved
AliasesPYM
Ensembl geneENSG00000170473
Ensembl biotypeprotein_coding
OMIM619753
Entrez84305

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000302533, ENST00000398213, ENST00000408946, ENST00000454792, ENST00000547925, ENST00000549939, ENST00000557259, ENST00000859965

RefSeq mRNA: 2 — MANE Select: NM_032345 NM_001143853, NM_032345

CCDS: CCDS41795, CCDS44916

Canonical transcript exons

ENST00000408946 — 3 exons

ExonStartEnd
ENSE000011433515590141355902355
ENSE000015685055592772555927894
ENSE000035604355590338755903480

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 95.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.3793 / max 165.9154, expressed in 1816 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter IDTPM avgSamples expressed
13145013.30401756
13144711.07521785
1314483.46781430
1314490.9620600
1314530.3615136
1314520.208892

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
lower esophagus mucosaUBERON:003583495.77gold quality
esophagus mucosaUBERON:000246995.30gold quality
mucosa of transverse colonUBERON:000499194.95gold quality
upper arm skinUBERON:000426394.09gold quality
olfactory segment of nasal mucosaUBERON:000538693.46gold quality
pharyngeal mucosaUBERON:000035593.45gold quality
kidney epitheliumUBERON:000481993.28silver quality
tibialis anteriorUBERON:000138592.99gold quality
skin of legUBERON:000151192.87gold quality
skin of abdomenUBERON:000141692.50gold quality
esophagusUBERON:000104392.33gold quality
granulocyteCL:000009491.70gold quality
rectumUBERON:000105291.65gold quality
islet of LangerhansUBERON:000000691.54gold quality
right lobe of liverUBERON:000111491.51gold quality
right adrenal gland cortexUBERON:003582791.48gold quality
minor salivary glandUBERON:000183091.40gold quality
left adrenal glandUBERON:000123491.38gold quality
right adrenal glandUBERON:000123391.31gold quality
epithelial cell of pancreasCL:000008391.21gold quality
left adrenal gland cortexUBERON:003582591.19gold quality
leukocyteCL:000073891.17gold quality
monocyteCL:000057691.01gold quality
pancreatic ductal cellCL:000207990.94gold quality
zone of skinUBERON:000001490.93gold quality
transverse colonUBERON:000115790.90gold quality
adrenal cortexUBERON:000123590.90gold quality
lymph nodeUBERON:000002990.79gold quality
small intestine Peyer’s patchUBERON:000345490.79gold quality
mouth mucosaUBERON:000372990.79gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-MTAB-6524no99.87
E-ANND-3no0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting PYM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-5196-5P100.0067.982761
HSA-MIR-4747-5P100.0067.902681
HSA-MIR-4425100.0067.591049
HSA-MIR-4510100.0066.602050
HSA-MIR-6127100.0066.762188
HSA-MIR-6129100.0066.462080
HSA-MIR-6130100.0066.692012
HSA-MIR-6133100.0066.482064
HSA-MIR-4533100.0069.482758
HSA-MIR-515-5P99.9269.822343
HSA-MIR-519E-5P99.9269.622358
HSA-MIR-15A-5P99.9072.802787
HSA-MIR-15B-5P99.9072.782798
HSA-MIR-16-5P99.9072.802780
HSA-MIR-195-5P99.9072.812805
HSA-MIR-6838-5P99.8971.942690
HSA-MIR-4728-5P99.8569.394718
HSA-MIR-6785-5P99.8268.684428
HSA-MIR-6885-3P99.7570.363187
HSA-MIR-149-3P99.7268.223963
HSA-MIR-6883-5P99.6968.053785
HSA-MIR-613499.6365.681537
HSA-MIR-6716-5P99.5668.621244
HSA-MIR-17-3P99.5566.771311
HSA-MIR-766-5P99.4767.912225
HSA-MIR-569599.4167.481047
HSA-MIR-6739-3P99.2268.841843
HSA-MIR-429199.2068.882969
HSA-MIR-6852-5P99.1766.692073
HSA-MIR-92299.0267.231838

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 29.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

  • suggest that PYM functions as a bridge between EJC-bearing spliced mRNAs and the translation machinery to enhance translation of the mRNAs (PMID:18026120)
  • PYM is an Exon junction complexes(EJC) disassembly factor that acts both in vitro and in living cells, and that antagonizes important EJC functions. (PMID:19410547)

Cross-species orthologs

7 orthologs

OrganismSymbolGene ID
danio_reriopym1ENSDARG00000046024
mus_musculusPym1ENSMUSG00000064030
rattus_norvegicusPym1ENSRNOG00000058130
rattus_norvegicusENSRNOG00000079680
rattus_norvegicusENSRNOG00000087436
drosophila_melanogasterPymFBGN0034918
caenorhabditis_elegansWBGENE00011871

Protein

Protein identifiers

Partner of Y14 and magoQ9BRP8 (reviewed: Q9BRP8)

Alternative names: PYM homolog 1 exon junction complex-associated factor, Protein wibg homolog

All UniProt accessions (3): Q9BRP8, F8VT68, H0YJW5

UniProt curated annotations — full annotation on UniProt →

Function. Key regulator of the exon junction complex (EJC), a multiprotein complex that associates immediately upstream of the exon-exon junction on mRNAs and serves as a positional landmark for the intron exon structure of genes and directs post-transcriptional processes in the cytoplasm such as mRNA export, nonsense-mediated mRNA decay (NMD) or translation. Acts as an EJC disassembly factor, allowing translation-dependent EJC removal and recycling by disrupting mature EJC from spliced mRNAs. Its association with the 40S ribosomal subunit probably prevents a translation-independent disassembly of the EJC from spliced mRNAs, by restricting its activity to mRNAs that have been translated. Interferes with NMD and enhances translation of spliced mRNAs, probably by antagonizing EJC functions. May bind RNA; the relevance of RNA-binding remains unclear in vivo, RNA-binding was detected by PubMed:14968132, while PubMed:19410547 did not detect RNA-binding activity independently of the EJC.

Subunit / interactions. Interacts (via N-terminus) with MAGOH and RBM8A; the interaction is direct. Associates (eIF2A-like region) with the 40S ribosomal subunit and the 48S preinitiation complex.

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Nucleoplasm.

Domain organisation. The eIF2A-like region shares sequence similarity with eIF2A and mediates the interaction with the 40S ribosomal subunit and the 48S preinitiation complex.

Similarity. Belongs to the pym family.

Isoforms (2)

UniProt IDNamesCanonical?
Q9BRP8-11yes
Q9BRP8-22

RefSeq proteins (2): NP_001137325, NP_115721* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR015362WIBG_mago-bdDomain
IPR036348WIBG_N_sfHomologous_superfamily
IPR039333PYM1Family

Pfam: PF09282

UniProt features (18 total): modified residue 5, region of interest 4, compositionally biased region 3, coiled-coil region 2, chain 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9BRP8-F176.010.36

Functional residue map

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

Post-translational modifications (5): 1, 6, 64, 72, 117

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 142 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, AREB6_03, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACTGCAG_MIR173P, YY1_Q6, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CCANNAGRKGGC_UNKNOWN, SOX9_B1, IRF1_Q6, IRF_Q6, AACTTT_UNKNOWN, RYTTCCTG_ETS2_B, TCCAGAG_MIR518C, ELK1_01

GO Biological Process (4): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), positive regulation of translation (GO:0045727), exon-exon junction complex disassembly (GO:1903259), regulation of translation (GO:0006417)

GO Molecular Function (3): RNA binding (GO:0003723), ribosome binding (GO:0043022), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), cell junction (GO:0030054), exon-exon junction complex (GO:0035145), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
translation2
nuclear lumen2
nuclear-transcribed mRNA catabolic process1
regulation of translation1
positive regulation of gene expression1
positive regulation of protein metabolic process1
protein-containing complex disassembly1
post-transcriptional regulation of gene expression1
regulation of protein metabolic process1
nucleic acid binding1
ribonucleoprotein complex binding1
binding1
intracellular membraneless organelle1
intracellular anatomical structure1
cytoplasm1
nuclear protein-containing complex1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

792 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
PYM1MAGOHBQ96A72964
PYM1MAGOHP50606964
PYM1RBM8AQ9Y5S9705
PYM1UPF3BQ9BZI7618
PYM1EIF4A3P38919597
PYM1UPF1Q92900543
PYM1UPF2Q9HAU5524
PYM1UPF3AQ9H1J1449
PYM1ADCY10Q96PN6420
PYM1STOML2Q9UJZ1419
PYM1CASC3O15234407
PYM1SEC63Q9UGP8386
PYM1SUOXP51687386
PYM1SMG7Q92540382
PYM1AAR2Q9Y312376

IntAct

132 interactions, top by confidence:

ABTypeScore
CASC3EIF4A3psi-mi:“MI:0915”(physical association)0.980
RBM8AMAGOHpsi-mi:“MI:0915”(physical association)0.980
RBM8AMAGOHpsi-mi:“MI:0914”(association)0.980
MAGOHCASC3psi-mi:“MI:0914”(association)0.970
CDKN2CCDK4psi-mi:“MI:0914”(association)0.970
PYM1MAGOHpsi-mi:“MI:0914”(association)0.940
PYM1MAGOHpsi-mi:“MI:0915”(physical association)0.940
MAGOHPYM1psi-mi:“MI:0914”(association)0.940
MAGOHPYM1psi-mi:“MI:0915”(physical association)0.940
MAGOHEIF4A3psi-mi:“MI:0914”(association)0.940
RBM8ACASC3psi-mi:“MI:0914”(association)0.900
LARP7CCNT1psi-mi:“MI:0914”(association)0.850
MOB1BLATS1psi-mi:“MI:0914”(association)0.840
NHNRNPRpsi-mi:“MI:0914”(association)0.730
CDALIN7Apsi-mi:“MI:0914”(association)0.640
PYM1CASC3psi-mi:“MI:0914”(association)0.620

BioGRID (189): RTN4IP1 (Two-hybrid), WIBG (Affinity Capture-RNA), WIBG (Affinity Capture-RNA), WIBG (Affinity Capture-MS), WIBG (Affinity Capture-MS), WIBG (Affinity Capture-MS), NELFE (Co-fractionation), WIBG (Co-fractionation), WIBG (Co-fractionation), WIBG (Co-fractionation), RTN4IP1 (Two-hybrid), WIBG (Affinity Capture-MS), WIBG (Affinity Capture-MS), WIBG (Affinity Capture-MS), WIBG (Affinity Capture-MS)

ESM2 similar proteins: A1A4P4, A1CH36, A2ALW5, A5AAL8, B0BN56, O42911, O70279, P0C2B7, P58468, P83565, Q0CLE8, Q1ECT8, Q290P4, Q2GVC2, Q3SZ86, Q4G0I0, Q4V7Q1, Q5B4U6, Q5BJW9, Q5RFR4, Q5XJW2, Q61733, Q6RUT7, Q753F1, Q7SDU5, Q7SHR9, Q80ZS3, Q86TS9, Q8BGX2, Q8BK72, Q8CHP5, Q8SPE7, Q8TAE8, Q8VD26, Q8WUQ7, Q96AN5, Q96DF8, Q9BRP8, Q9BSF4, Q9BYN8

Diamond homologs: A6QPH1, B0WII7, B1WB17, B4NSP6, B5XDD3, B5XG19, P82804, Q16LW2, Q2F5J3, Q640E9, Q6PH11, Q7Q6B5, Q8CHP5, Q9BRP8, Q9LPZ4, Q5ZKC1, Q4QRJ7, Q8BJW6, Q9BY44

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 137 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:

PathwayPartnersFoldFDR
Nonsense-Mediated Decay (NMD)1026.2×3e-10
Eukaryotic Translation Initiation724.3×2e-07
Cap-dependent Translation Initiation724.3×2e-07
SARS-CoV-1 modulates host translation machinery724.3×2e-07
Eukaryotic Translation Elongation721.9×5e-07
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S721.4×5e-07
SARS-CoV-2 modulates host translation machinery820.1×1e-07
Influenza Viral RNA Transcription and Replication819.4×2e-07

GO biological processes:

GO termPartnersFoldFDR
cytoplasmic translation1319.6×8e-11
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay519.0×5e-04
mRNA export from nucleus716.8×3e-05
ribosomal small subunit biogenesis713.0×1e-04
rRNA processing1112.7×3e-07
regulation of alternative mRNA splicing, via spliceosome59.9×9e-03
translation108.3×5e-05
mRNA splicing, via spliceosome107.5×1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance8
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

865 predictions. Top by Δscore:

VariantEffectΔscore
12:55902351:CATAT:Cacceptor_gain1.0000
12:55903370:AAAG:Adonor_gain1.0000
12:55903385:A:ACdonor_gain1.0000
12:55903385:A:ATdonor_loss1.0000
12:55903386:C:CCdonor_gain1.0000
12:55903386:CA:Cdonor_gain1.0000
12:55903396:T:TAdonor_gain1.0000
12:55903399:T:TAdonor_gain1.0000
12:55903412:AT:Adonor_gain1.0000
12:55903413:T:Cdonor_gain1.0000
12:55903413:T:TAdonor_gain1.0000
12:55903476:CTTGC:Cacceptor_gain1.0000
12:55903477:TTGC:Tacceptor_gain1.0000
12:55903478:TGCCT:Tacceptor_loss1.0000
12:55903479:GC:Gacceptor_gain1.0000
12:55903479:GCCTA:Gacceptor_loss1.0000
12:55903480:CC:Cacceptor_gain1.0000
12:55903480:CCTAA:Cacceptor_loss1.0000
12:55903481:C:Aacceptor_loss1.0000
12:55903481:C:CCacceptor_gain1.0000
12:55902353:TAT:Tacceptor_gain0.9900
12:55902353:TATC:Tacceptor_loss0.9900
12:55902354:ATCTG:Aacceptor_loss0.9900
12:55902355:TCTG:Tacceptor_loss0.9900
12:55902356:C:CCacceptor_gain0.9900
12:55902356:CTGCA:Cacceptor_loss0.9900
12:55902357:T:Gacceptor_loss0.9900
12:55903379:CCA:Cdonor_gain0.9900
12:55903384:TAC:Tdonor_gain0.9900
12:55903385:ACA:Adonor_gain0.9900

AlphaMissense

1303 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
12:55903439:G:TR27S1.000
12:55902354:A:CY45D0.999
12:55902354:A:GY45H0.999
12:55903447:C:AG24V0.999
12:55903447:C:TG24E0.999
12:55903448:C:AG24W0.999
12:55902346:G:CN47K0.998
12:55902346:G:TN47K0.998
12:55902354:A:TY45N0.998
12:55903419:T:AK33N0.998
12:55903419:T:GK33N0.998
12:55903471:A:TI16N0.998
12:55901987:A:GL167P0.997
12:55902017:A:GL157P0.997
12:55903393:A:TV42D0.997
12:55903412:A:GY36H0.997
12:55903415:C:GG35R0.997
12:55903415:C:TG35R0.997
12:55903434:C:AK28N0.997
12:55903434:C:GK28N0.997
12:55903438:C:GR27P0.997
12:55903451:C:GD23H0.997
12:55901931:T:CK186E0.996
12:55902005:A:GL161P0.996
12:55902009:T:CK160E0.996
12:55902012:T:CK159E0.996
12:55902222:G:TR89S0.996
12:55902347:T:AN47I0.996
12:55902353:T:CY45C0.996
12:55903405:G:TP38H0.996

dbSNP variants (sampled 300 via entrez): RS1000000622 (12:55926607 A>C), RS1000160488 (12:55925061 C>T), RS1000165254 (12:55902108 C>T), RS1000181334 (12:55920841 T>C), RS1000260623 (12:55924795 A>T), RS1000282407 (12:55908856 A>C), RS1000398860 (12:55926879 C>A,G), RS1000552715 (12:55905656 T>C,G), RS1000578731 (12:55925708 GCAGTTTATTCCTTTTTCTCTTC>G), RS1000648158 (12:55921772 A>G), RS1000792386 (12:55918728 C>T), RS1000956503 (12:55921945 C>T), RS1000989935 (12:55913233 A>T), RS1000995049 (12:55927826 C>T), RS1001003427 (12:55901039 G>A)

Disease associations

OMIM: gene MIM:619753 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST010002_217Refractive error6.000000e-174

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066359 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
5.14Kd7239nMCHEMBL5653589
5.14ED507239nMCHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149782: Binding affinity to human WIBG incubated for 45 mins by Kinobead based pull down assaykd7.2391uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects expression, decreases expression, decreases methylation4
bisphenol Adecreases expression, increases expression2
Benzo(a)pyrenedecreases expression2
Cisplatinaffects cotreatment, increases expression2
p-Chloromercuribenzoic Acidaffects cotreatment, decreases expression2
GSK-J4decreases expression1
FR900359decreases phosphorylation1
bisphenol Fincreases expression1
methylmercuric chloridedecreases expression1
pyrogallol 1,3-dimethyl etherdecreases expression, affects localization, increases expression, affects cotreatment1
trichostatin Aaffects expression1
tetrahydropalmatinedecreases expression1
arseniteincreases reaction, affects binding1
sodium arsenitedecreases expression1
di-n-butylphosphoric acidaffects expression1
2,3,5-(triglutathion-S-yl)hydroquinoneincreases ADP-ribosylation1
CGP 52608affects binding, increases reaction1
scriptaiddecreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression1
Grape Seed Proanthocyanidinsaffects cotreatment, decreases expression1
dorsomorphinaffects cotreatment, decreases expression1
jinfukangaffects cotreatment, increases expression1
bisphenol AFincreases expression1
Sunitinibdecreases expression1
Panobinostatdecreases expression1
Caffeinedecreases phosphorylation1
Cannabidiolincreases expression1
Catechinaffects cotreatment, decreases expression1
Deoxyglucoseincreases expression1
Doxorubicindecreases expression1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5652824BindingBinding affinity to human WIBG incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_B3FHAbcam HEK293T PYM1 KOTransformed cell lineFemale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.