PABPN1

Summary

PABPN1 (poly(A) binding protein nuclear 1, HGNC:8565) is a protein-coding gene on chromosome 14q11.2, encoding Polyadenylate-binding protein 2 (Q86U42). Involved in the 3’-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream cleavage product. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene encodes an abundant nuclear protein that binds with high affinity to nascent poly(A) tails. The protein is required for progressive and efficient polymerization of poly(A) tails at the 3’ ends of eukaryotic transcripts and controls the size of the poly(A) tail to about 250 nt. At steady-state, this protein is localized in the nucleus whereas a different poly(A) binding protein is localized in the cytoplasm. This gene contains a GCG trinucleotide repeat at the 5’ end of the coding region, and expansion of this repeat from the normal 6 copies to 8-13 copies leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease. Related pseudogenes have been identified on chromosomes 19 and X. Read-through transcription also exists between this gene and the neighboring upstream BCL2-like 2 (BCL2L2) gene.

Source: NCBI Gene 8106 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oculopharyngeal muscular dystrophy (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 6 total — 1 pathogenic
• Phenotypes (HPO): 38
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_004643

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8565
Approved symbol	PABPN1
Name	poly(A) binding protein nuclear 1
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	PAB2
Ensembl gene	ENSG00000100836
Ensembl biotype	protein_coding
OMIM	602279
Entrez	8106

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 retained_intron

ENST00000216727, ENST00000397276, ENST00000553960, ENST00000554062, ENST00000555295, ENST00000556809, ENST00000556821, ENST00000557702, ENST00000925891

RefSeq mRNA: 3 — MANE Select: NM_004643 NM_001360551, NM_001360552, NM_004643

CCDS: CCDS86374, CCDS86375, CCDS9592

Canonical transcript exons

ENST00000216727 — 7 exons

Exon	Start	End
ENSE00001099644	23325247	23326163
ENSE00001528016	23321457	23321820
ENSE00003459464	23324138	23324289
ENSE00003484153	23322181	23322295
ENSE00003491053	23323377	23323483
ENSE00003617767	23323965	23324052
ENSE00003648395	23322999	23323066

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.4577 / max 832.9894, expressed in 1826 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138892	53.7725	1826
138895	5.0227	1415
138893	2.1875	1218
138894	1.6770	882
138897	0.5844	290
138896	0.2075	79
138891	0.0061	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	99.30	gold quality
left testis	UBERON:0004533	99.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.14	gold quality
right uterine tube	UBERON:0001302	99.04	gold quality
cerebellar hemisphere	UBERON:0002245	99.03	gold quality
cerebellar cortex	UBERON:0002129	98.98	gold quality
adenohypophysis	UBERON:0002196	98.88	gold quality
body of uterus	UBERON:0009853	98.76	gold quality
right lobe of thyroid gland	UBERON:0001119	98.71	gold quality
left lobe of thyroid gland	UBERON:0001120	98.71	gold quality
ganglionic eminence	UBERON:0004023	98.70	gold quality
sural nerve	UBERON:0015488	98.64	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.59	gold quality
left uterine tube	UBERON:0001303	98.58	gold quality
metanephros cortex	UBERON:0010533	98.58	gold quality
right ovary	UBERON:0002118	98.57	gold quality
right frontal lobe	UBERON:0002810	98.54	gold quality
peripheral nervous system	UBERON:0000010	98.53	gold quality
nerve	UBERON:0001021	98.53	gold quality
tibial nerve	UBERON:0001323	98.53	gold quality
ventricular zone	UBERON:0003053	98.50	gold quality
left ovary	UBERON:0002119	98.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.47	gold quality
stromal cell of endometrium	CL:0002255	98.41	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.41	gold quality
endocervix	UBERON:0000458	98.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.39	gold quality
lower esophagus	UBERON:0013473	98.38	gold quality
body of stomach	UBERON:0001161	98.35	gold quality
right adrenal gland cortex	UBERON:0035827	98.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting PABPN1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• The autosomal dominant form of this disease is caused by short expansions of a (GCG)(6) repeat to (GCG)(8-13) in the PABPN1 gene. (PMID:11689481)
• In COS-7 cells, predominantly nuclear protein hnRNP A1 and A/B co-localize with mPABPN1 in insoluble intranuclear aggregates. (PMID:12945950)
• All families carrying the mutation (GCG)(11)(GCA)(3)(GCG) shared a common ancestral haplotype and the age of the mutation was estimated in 37-53 generations by a composite likelihood method. (PMID:15694141)
• a 64 year old Chinese-Malaysian woman who presented with progressive dysphagia and bilateral ptosis for about 6 years. and showed repeat expansion in one allele to (GCG)9 while normal in the other (GCG)6. (PMID:15725589)
• Expanded PABPN1, presumably via the toxic effects of its polyalanine tract, leads to inclusion formation and neurodegeneration in both the transgenic mouse and the human. (PMID:15755680)
• Cytoplasmic targeting of mutant PABPN1 suppresses protein aggregation and toxicity in oculopharyngeal muscular dystrophy. (PMID:16101680)
• Recruitment of HSP70 and HSC70 into the cell nucleus reduced mutant PABPN1 aggregation in a HeLa cell culture model. (PMID:16239242)
• PABPN1 has a role in myogenesis (PMID:16378590)
• Overexpression of either the wild type or mutant PABPN1 slowed down cell proliferation. The slowing down of proliferation together with the occasional occurrence of apoptosis could contribute in vivo to the late onset of this disease. (PMID:16860991)
• Mutation of the PABPN1 in oculopharyngeal muscular dystrophy (OPMD) provokes premature senescence in dividing myoblasts, that may be due to intranuclear toxic aggregates. (PMID:17005403)
• the N-terminal domain of PABPN1 has a role in oculopharyngeal muscular dystrophy (PMID:17229142)
• This is the first report directly indicating that nuclear aggregation in OPMD may reflect an active process by which cells sequester and inactivate the soluble toxic form of expPABPN1. (PMID:17418585)
• An Italy case of oculopharyngeal muscular dystrophy in PABNPN1 mutation. (PMID:18175083)
• Wild-type PABPN1 over-expression can reduce mutant PABPN1 toxicity in both cell and mouse models of Oculopharyngeal muscular dystrophy. (PMID:18178579)
• We report a unique PABPN1 gene mutation in a large Bulgarian family with OPMD. (PMID:18274805)
• Expression of additional HSPs including HSP27, HSP40, and HSP105 were induced in mutant PABPN1 expressing cells following exposure to the chemicals mentioned above. (PMID:18343218)
• PABPN1 transgenic nematodes show muscle cell degeneration and abnormal motility. (PMID:18397876)
• C-terminal domain containing the methylated arginine residues is known to promote PAPBN1 self-association, and arginine methylation has been reported to inhibit self-association of an orthologous protein (PMID:18495660)
• results suggest that OPMD in the Mexican population is mostly due to (GCG)(11) or (GCG)(9) PABPN1 expanded alleles arising from two independent founder effect mutations. (PMID:18577654)
• PABPN1 protein is associated with oculopharyngeal muscular dystrophy. (PMID:18577936)
• in contrast to a single GCG expansion in most of oculopharyngeal muscular dystrophy (OPMD) patients in the literature, an insertion of (GCG)4GCA in the PABPN1 gene was found in the Taiwanese OPMD subjects (PMID:19101703)
• results suggest that the pathological mutation in the PABPN1 gene alters the protein conformation and induces a preferential interaction with type I PRMTs and Hsp70 chaperones (PMID:19641605)
• no correlation was found between muscle weakness, the frequency of repeats in the polyadenine binding protein nuclear , and the frequency and size of nuclear inclusions (PMID:21545772)
• A GCG expansion (GCG)11 in polyadenylate-binding protein nuclear 1 gene caused oculopharyngeal muscular dystrophy in a Chinese family. (PMID:21647273)
• Transportin binding might delay methylation of PABPN1 until after nuclear import. (PMID:21808065)
• In myotubes, the ratio of soluble/insoluble expPABPN1 is significantly lower compared with that of the WT protein. (PMID:21854744)
• Taken together, the present data suggest that heterozygote OPMD patients may show some cognitive impairments and psychological disorders (PMID:21956377)
• Concerning the frequency of the expanded (GCN)11 polymorphism in PABPN1, all 34 patients have the normal allele, correlating genotypic and phenotypic features. (PMID:22231868)
• Time-lapse experiments in cultured myoblasts confirm nuclear speckles as biogenesis sites of PABPN1 inclusions in oculopharyngeal muscular dystrophy. (PMID:22249111)
• Results elucidate a novel function for PABPN1 as a suppressor of alternative cleavage and polyadenylation. (PMID:22502866)
• PABPN1 with a 17 alanine expansion generates stress that initiates apoptosis through a p53-dependent mechanism. (PMID:22519734)
• Fibrillar PABPN1 has a structure that differs from native PABPN1 and circumstantial evidence is presented that the C-terminal domain is involved in fibril formation. (PMID:22570486)
• we show that PABPN1 promotes lncRNA turnover via a polyadenylation-dependent mechanism (PMID:23166521)
• although function of PABPN1 may be compensated by nuclear translocation of PABP4 and perhaps by increase the cytoplasmic abundance of PABP5, these were not sufficient to prevent apoptosis of cells. PABPN1 may have an anti apoptotic role in mammalian cells (PMID:23300856)
• These results suggest that PABPN1 levels regulate muscle cell aging and oculopharyngeal muscular dystrophy represents an accelerated muscle aging disorder. (PMID:23793615)
• We show that ARIH2 E3-ligase regulates PABPN1 protein accumulation and aggregation (PMID:24486325)
• Loss of PABPN1, a suppressor of APA, might promote tumor aggressiveness by releasing the cancer cells from microRNA-mediated gene regulation. (PMID:24975429)
• the first step of the cleavage and polyadenylation reaction, mRNA cleavage, is affected in muscles expressing alanine-expanded PABPN1. We propose that impaired cleavage is an early defect in Oculopharyngeal muscular dystrophy. (PMID:25816335)
• The ability of PABPN1 to promote splicing requires its RNA binding and, to a lesser extent, poly(A)polymerase (PAP) - stimulatory functions. (PMID:25896913)
• PABPN1 inhibits expression of transcripts with pAs near the transcription start site (TSS), a property possibly related to its role in RNA degradation (PMID:25906188)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pabpn1	ENSDARG00000045373
mus_musculus	Pabpn1	ENSMUSG00000022194
rattus_norvegicus	Pabpn1	ENSRNOG00000042195
drosophila_melanogaster	Pabp2	FBGN0005648
caenorhabditis_elegans	pabp-2	WBGENE00003904

Paralogs (1): PABPN1L (ENSG00000205022)

Protein

Protein identifiers

Polyadenylate-binding protein 2 — Q86U42 (reviewed: Q86U42)

Alternative names: Nuclear poly(A)-binding protein 1, Poly(A)-binding protein II, Polyadenylate-binding nuclear protein 1

All UniProt accessions (4): Q86U42, B4DEH8, G3V4T2, H0YJH9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the 3’-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream cleavage product. Stimulates poly(A) polymerase (PAPOLA) conferring processivity on the poly(A) tail elongation reaction and also controls the poly(A) tail length. Increases the affinity of poly(A) polymerase for RNA. Is also present at various stages of mRNA metabolism including nucleocytoplasmic trafficking and nonsense-mediated decay (NMD) of mRNA. Cooperates with SKIP to synergistically activate E-box-mediated transcription through MYOD1 and may regulate the expression of muscle-specific genes. Binds to poly(A) and to poly(G) with high affinity. May protect the poly(A) tail from degradation. Subunit of the trimeric poly(A) tail exosome targeting (PAXT) complex, a complex that directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor MTREX, which links to RNA-binding protein adapters.

Subunit / interactions. May interact with SETX. Monomer and homooligomer. Binds RNA as a monomer and oligomerizes when bound to poly(A). Interacts with PAPOLA, but only in presence of oligo(A) RNA. Interacts with transportin. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Association in a ternary complex with CPSF4 and influenza A virus NS1 blocks pre-mRNAs processing, thereby preventing nuclear export of host cell mRNAs. Associates in a single complex with SKIP and MYOD1 and interacts with SKIP in differentiated myocytes. Interacts with NUDT21/CPSF5. Interacts (via RRM domain and C-terminal arginine-rich region) with ZFP36 (via hypophosphorylated form); this interaction occurs in the nucleus in a RNA-independent manner, decreases in presence of single-stranded poly(A) RNA-oligomer and in a p38-dependent-manner and may down-regulated RNA poly(A) polymerase activity. Component of the poly(A) tail exosome targeting (PAXT) complex made of accessory factors, such as PABPN1, ZFC3H1 and MTREX. Interacts with ZFC3H1 in a RNase-insensitive manner. Interacts with FRG1. Interacts with ZC3H11A.

Subcellular location. Nucleus. Cytoplasm. Nucleus speckle.

Tissue specificity. Ubiquitous.

Post-translational modifications. Arginine dimethylation is asymmetric and involves PRMT1 and PRMT3. It does not influence the RNA binding properties.

Disease relevance. Oculopharyngeal muscular dystrophy 1 (OPMD1) [MIM:164300] An autosomal dominant, late-onset, slowly progressive myopathy characterized by eyelid ptosis, dysphagia and, sometimes by other cranial and limb-muscle involvement. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The RRM domain is essential for specific adenine bases recognition in the poly(A) tail but not sufficient for poly(A) binding.

Polymorphism. The poly-Ala region of PABPN1 is polymorphic (6-7 repeats) in the population and is expanded to 8-13 repeats in OPMD1 patients. Compound heterozygotes for (GCG)9 mutation and a (GCG)7 allele result in earlier onset and more severe clinical manifestations of the disease.

Miscellaneous. The association of the expanded polyalanine mutations together with the capability to oligomerize may induce intranuclear inclusions and cell death. Expanded polyalanine mutations may either result from unequal crossing over during germ cell homologous recombination or from DNA slippage. The pathogenic mechanisms mediated by polyalanine expansion mutations may be either a general disruption of cellular RNA metabolism due to the trapping by the inclusions of PABPN1, mRNAs and/or nuclear proteins, resulting in the induction of cell death; or may change the normal muscle cell differentiation. May be due to a competing donor splice site.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86U42-1	1	yes
Q86U42-2	2
Q92843-2	3, BCL2L2-PABPN1

RefSeq proteins (3): NP_001347480, NP_001347481, NP_004634* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (53 total): modified residue 24, region of interest 5, helix 5, strand 5, compositionally biased region 4, splice variant 2, mutagenesis site 2, initiator methionine 1, chain 1, domain 1, sequence variant 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3UCG	X-RAY DIFFRACTION	1.95
3B4D	X-RAY DIFFRACTION	2
3B4M	X-RAY DIFFRACTION	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86U42-F1	68.57	0.27

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 (24): 2, 17, 19, 52, 95, 150, 235, 238, 238, 259, 259, 263, 263, 265, 267, 269, 277, 279, 287, 289 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
213–220	abolishes self-association, protein aggregation and cell death.
301–306	abolishes self-association, protein aggregation and cell death.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-168315	Inhibition of Host mRNA Processing and RNA Silencing
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-77595	Processing of Intronless Pre-mRNAs
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9820865	Z-decay: degradation of maternal mRNAs by zygotically expressed factors
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9930044	Nuclear RNA decay
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA

MSigDB gene sets: 324 (showing top): MORF_MTA1, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_CDK2, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, MORF_HDAC2, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, COUP_01, GOBP_NUCLEAR_TRANSPORT, MORF_TERF1

GO Biological Process (7): MAPK cascade (GO:0000165), RNA processing (GO:0006396), mRNA processing (GO:0006397), muscle contraction (GO:0006936), poly(A)+ mRNA export from nucleus (GO:0016973), cellular response to lipopolysaccharide (GO:0071222), positive regulation of polynucleotide adenylyltransferase activity (GO:1904247)

GO Molecular Function (5): RNA binding (GO:0003723), poly(A) binding (GO:0008143), RNA polymerase binding (GO:0070063), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607), nuclear inclusion body (GO:0042405), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Metabolism of RNA	2
NS1 Mediated Effects on Host Pathways	1
Processing of Capped Intron-Containing Pre-mRNA	1
RNA Polymerase II Transcription	1
Processing of Capped Intronless Pre-mRNA	1
mRNA 3’-end processing	1
Maternal to zygotic transition (MZT)	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
intracellular signaling cassette	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA processing	1
mRNA metabolic process	1
muscle system process	1
mRNA export from nucleus	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
positive regulation of catalytic activity	1
regulation of transferase activity	1
poly(A) RNA polymerase activity	1
nucleic acid binding	1
poly-purine tract binding	1
enzyme binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
nucleus	1
inclusion body	1
protein-containing complex	1

Protein interactions and networks

STRING

2394 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PABPN1	ELAVL1	Q15717	978
PABPN1	ZFC3H1	O60293	977
PABPN1	PAPOLA	P51003	940
PABPN1	PABPC1	P11940	923
PABPN1	PABPC4	Q13310	912
PABPN1	PAPOLG	Q9BWT3	895
PABPN1	PAPOLB	Q9NRJ5	892
PABPN1	MTREX	P42285	883
PABPN1	PABPC5	Q96DU9	875
PABPN1	PABPC4L	P0CB38	874
PABPN1	PABPC1L2A	Q5JQF8	871
PABPN1	PABPC1L	Q4VXU2	870
PABPN1	ZC3H14	Q6PJT7	870
PABPN1	NCBP2	P52298	859
PABPN1	PABPC3	Q9H361	856

IntAct

146 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0915”(physical association)	0.770
PABPN1	SNW1	psi-mi:“MI:0915”(physical association)	0.700
SNW1	PABPN1	psi-mi:“MI:0403”(colocalization)	0.700
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
YBX1	DDX3X	psi-mi:“MI:0914”(association)	0.610
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
PABPN1	PABPC1	psi-mi:“MI:0914”(association)	0.500
PABPC1	PABPN1	psi-mi:“MI:0915”(physical association)	0.500
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
DLG1	PABPN1	psi-mi:“MI:0407”(direct interaction)	0.440
MET	NDUFA4	psi-mi:“MI:2364”(proximity)	0.420
YWHAZ	PABPN1	psi-mi:“MI:0915”(physical association)	0.400
PABPN1	MYCBP2	psi-mi:“MI:0915”(physical association)	0.370
SMARCA4	PABPN1	psi-mi:“MI:0915”(physical association)	0.370
DNAJB4	PABPN1	psi-mi:“MI:0915”(physical association)	0.370
	PABPN1	psi-mi:“MI:0915”(physical association)	0.370
ATR	YBX3	psi-mi:“MI:0914”(association)	0.350
Prmt6	LAMA1	psi-mi:“MI:0914”(association)	0.350
BACH1		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350

BioGRID (259): PABPN1 (Affinity Capture-Western), ARIH2 (Affinity Capture-Western), PABPN1 (Protein-peptide), PABPN1 (Affinity Capture-MS), PABPN1 (Affinity Capture-MS), PABPN1 (Affinity Capture-MS), PABPN1 (Affinity Capture-MS), EIF6 (Co-fractionation), PABPN1 (Affinity Capture-MS), PABPN1 (Proximity Label-MS), PABPN1 (Affinity Capture-MS), PABPN1 (Affinity Capture-MS), PABPN1 (Affinity Capture-MS), PABPN1 (Affinity Capture-MS), PABPN1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ4, A1L443, A2APT9, A2IDD5, A6NDY0, A6NNL0, A7E321, B0BNE4, B1AL46, B1ASB6, E9PGG2, F5GYI3, G3V8Y7, O88286, Q14684, Q28165, Q3TYG6, Q3TYX8, Q3U3N6, Q49AM3, Q4V8C9, Q5R866, Q5RCJ6, Q5T7N3, Q5VT03, Q5VTJ3, Q5VZR2, Q5XFR0, Q60465, Q6ZMY3, Q6ZNE9, Q6ZUT6, Q6ZUX3, Q80VJ8, Q80VR2, Q86U42, Q8BSI6, Q8CCS6, Q8IVF1, Q8IY92

Diamond homologs: A0A0D1C8Z4, A2Q848, A6NDY0, A8WLV5, B0BNE4, B3LYP1, B3P0D7, B4JUT1, B4KCD5, B4LZ88, O13620, O13741, O13845, O14327, O80678, P19683, P19684, P20397, P33240, P38922, P40561, P42696, P49313, P49314, Q00916, Q05AT9, Q05CL8, Q06106, Q08208, Q08937, Q09295, Q09301, Q10B98, Q1PEP5, Q28165, Q28ZX3, Q44554, Q44556, Q44560, Q4G0J3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PABPN1	“up-regulates quantity by stabilization”	“messenger RNA”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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
mRNA 3’-end processing	9	17.7×	3e-07
mRNA Polyadenylation	16	14.1×	1e-11
Transport of Mature mRNA derived from an Intron-Containing Transcript	9	13.7×	2e-06
RNA Polymerase II Transcription Termination	6	13.2×	4e-04
snRNP Assembly	5	10.6×	4e-03
mRNA Splicing	9	9.9×	3e-05
Processing of Capped Intron-Containing Pre-mRNA	12	9.9×	5e-07
mRNA Splicing - Major Pathway	18	9.8×	7e-11

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	5	40.3×	5e-05
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	19.0×	6e-04
translational initiation	5	14.6×	1e-03
intrinsic apoptotic signaling pathway	5	14.6×	1e-03
mRNA export from nucleus	6	14.4×	4e-04
positive regulation of transcription elongation by RNA polymerase II	5	12.2×	3e-03
mRNA splicing, via spliceosome	15	11.2×	5e-09
mRNA transport	5	10.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
978416	NM_004643.3:c.3GGC[(8_13)]	Pathogenic

SpliceAI

830 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23321827:G:T	donor_gain	1.0000
14:23322170:A:AG	acceptor_gain	1.0000
14:23322176:A:AG	acceptor_gain	1.0000
14:23322176:ATTAG:A	acceptor_gain	1.0000
14:23322177:T:G	acceptor_gain	1.0000
14:23322177:TTA:T	acceptor_loss	1.0000
14:23322178:TA:T	acceptor_loss	1.0000
14:23322178:TAG:T	acceptor_loss	1.0000
14:23322179:A:AG	acceptor_gain	1.0000
14:23322180:G:GG	acceptor_gain	1.0000
14:23322180:GGA:G	acceptor_gain	1.0000
14:23322293:ATGGT:A	donor_loss	1.0000
14:23322294:TG:T	donor_gain	1.0000
14:23322294:TGG:T	donor_loss	1.0000
14:23322295:GG:G	donor_gain	1.0000
14:23322296:G:GG	donor_gain	1.0000
14:23322296:GTGA:G	donor_loss	1.0000
14:23322993:T:A	acceptor_gain	1.0000
14:23322993:T:TA	acceptor_gain	1.0000
14:23322996:TAGC:T	acceptor_loss	1.0000
14:23322997:A:AG	acceptor_gain	1.0000
14:23322997:A:C	acceptor_loss	1.0000
14:23322997:AGCT:A	acceptor_gain	1.0000
14:23322997:AGCTG:A	acceptor_gain	1.0000
14:23322998:G:GC	acceptor_gain	1.0000
14:23322998:G:GT	acceptor_gain	1.0000
14:23322998:GC:G	acceptor_gain	1.0000
14:23322998:GCT:G	acceptor_gain	1.0000
14:23322998:GCTG:G	acceptor_gain	1.0000
14:23322998:GCTGG:G	acceptor_gain	1.0000

AlphaMissense

1954 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23322185:T:A	L119Q	1.000
14:23322185:T:C	L119P	1.000
14:23322190:G:C	A121P	1.000
14:23322194:T:A	I122N	1.000
14:23322194:T:C	I122T	1.000
14:23322194:T:G	I122S	1.000
14:23322198:A:C	K123N	1.000
14:23322198:A:T	K123N	1.000
14:23322199:G:C	A124P	1.000
14:23322203:G:C	R125P	1.000
14:23322206:T:A	V126D	1.000
14:23322215:T:A	M129K	1.000
14:23322215:T:C	M129T	1.000
14:23322215:T:G	M129R	1.000
14:23322226:G:C	A133P	1.000
14:23322236:T:A	L136Q	1.000
14:23322236:T:C	L136P	1.000
14:23322245:T:C	L139P	1.000
14:23322248:A:C	Q140P	1.000
14:23323037:G:C	A169P	1.000
14:23323040:G:C	D170H	1.000
14:23323040:G:T	D170Y	1.000
14:23323041:A:C	D170A	1.000
14:23323041:A:G	D170G	1.000
14:23323041:A:T	D170V	1.000
14:23323042:T:A	D170E	1.000
14:23323042:T:G	D170E	1.000
14:23323046:C:A	R172S	1.000
14:23323047:G:C	R172P	1.000
14:23323049:T:C	S173P	1.000

dbSNP variants (sampled 300 via entrez): RS1000111277 (14:23323712 G>A,T), RS1000269007 (14:23323313 C>T), RS1000604744 (14:23322099 C>G), RS1001122950 (14:23325110 G>A,C), RS1001281527 (14:23324848 T>C), RS1001327693 (14:23322510 C>A,T), RS1001654624 (14:23322685 C>T), RS1002922017 (14:23324144 C>G,T), RS1003005467 (14:23322028 C>A,G,T), RS1003054369 (14:23322014 T>G), RS1003464070 (14:23326434 G>A), RS1003563002 (14:23321860 C>A,G,T), RS1003621299 (14:23326222 A>G,T), RS1004098600 (14:23324395 C>G), RS1005035543 (14:23320704 G>A,T)

Disease associations

OMIM: gene MIM:602279 | disease phenotypes: MIM:164300

GenCC curated gene-disease

Disease	Classification	Inheritance
oculopharyngeal muscular dystrophy	Definitive	Autosomal dominant
oculopharyngeal muscular dystrophy 1	Strong	Autosomal dominant

Mondo (2): oculopharyngeal muscular dystrophy 1 (MONDO:0958176), oculopharyngeal muscular dystrophy (MONDO:0008116)

Orphanet (0):

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000183	Tongue muscle weakness
HP:0000298	Mask-like facies
HP:0000467	Neck muscle weakness
HP:0000508	Ptosis
HP:0000602	Ophthalmoplegia
HP:0001260	Dysarthria
HP:0001288	Gait disturbance
HP:0001611	Hypernasal speech
HP:0001618	Dysphonia
HP:0002015	Dysphagia
HP:0002460	Distal muscle weakness
HP:0003198	Myopathy
HP:0003200	Ragged-red muscle fibers
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003302	Spondylolisthesis
HP:0003325	Limb-girdle muscle weakness
HP:0003327	Axial muscle weakness
HP:0003584	Late onset
HP:0003676	Progressive
HP:0003690	Limb muscle weakness
HP:0003701	Proximal muscle weakness
HP:0003805	Rimmed vacuoles
HP:0004303	Abnormal muscle fiber morphology
HP:0007838	Progressive ptosis
HP:0010535	Sleep apnea
HP:0010628	Facial palsy
HP:0011968	Feeding difficulties
HP:0012378	Fatigue
HP:0012473	Tongue atrophy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003248_4	Body mass index	3.000000e-06
GCST90000025_528	Appendicular lean mass	2.000000e-24
GCST90002388_130	Lymphocyte count	2.000000e-09
GCST90002406_416	Reticulocyte fraction of red cells	2.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D039141	Muscular Dystrophy, Oculopharyngeal	C05.651.534.500.450; C10.668.491.175.500.450; C16.320.577.450

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
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, 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
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Demecolcine	decreases expression	1
Estradiol	affects binding, increases reaction	1
Hydrogen Peroxide	affects expression	1
Ibuprofen	affects binding, decreases reaction	1
Indomethacin	affects binding, decreases reaction	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Vincristine	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 telomerase immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6B29	OPMDCl2	Telomerase immortalized cell line	Sex unspecified
CVCL_D2Z0	GM25477	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02015481	PHASE2	COMPLETED	Safety Tolerability and Efficacy Study of Cabaletta to Treat Oculopharyngeal Muscular Dystrophy (OPMD) Patients
NCT04226924	PHASE2	WITHDRAWN	Treatment of Oculopharyngeal Muscular Dystrophy With Trehalose
NCT06185673	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety and Clinical Activity of Intramuscular Doses of BB-301 Administered to Subjects With Oculopharyngeal Muscular Dystrophy With Dysphagia
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02158156	Not specified	UNKNOWN	Effect of Aerobic Training in Patients With Oculopharyngeal Muscular Dystrophy
NCT02877784	Not specified	COMPLETED	Screening in Oculopharyngeal Muscular Dystrophy
NCT03161847	Not specified	WITHDRAWN	Natural History Study of Oculopharyngeal Muscular Dystrophy
NCT03874910	Not specified	UNKNOWN	Pathology Analysis of OPMD Patient Myotomies
NCT04009408	Not specified	UNKNOWN	Expiratory Muscle Strength Training (EMST) in Neuromuscular Disorders
NCT07118280	Not specified	RECRUITING	Oral Health, Saliva Viscosity and Composition in Oculo-Pharyngeal Muscular Dystrophy (OPMD)
NCT07146256	Not specified	RECRUITING	Natural History of Oculo-Pharyngeal Muscular Dystrophy (OPMD) - Israel National OPMD Registry