PABPN1

poly(A) binding protein nuclear 1, the group of RNA binding motif containing

Basic information

Region (hg38): 14:23321457-23326163

Previous symbols: [ "OPMD", "PABP2" ]

Links

ENSG00000100836 ∙ NCBI:8106 ∙ OMIM:602279 ∙ HGNC:8565 ∙ Uniprot:Q86U42 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oculopharyngeal muscular dystrophy (Definitive), mode of inheritance: AD
• oculopharyngeal muscular dystrophy (Strong), mode of inheritance: AD
• oculopharyngeal muscular dystrophy (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oculopharyngeal muscular dystrophy 1	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	13997067; 13963574; 9462747; 11712939; 15725589; 15694141; 16648376; 20301305; 21647273; 21742497; 21956377; 22817818

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PABPN1 gene.

• not provided (5 variants)
• Oculopharyngeal muscular dystrophy (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PABPN1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	4	2	7
missense			22			22
nonsense						0
start loss						0
frameshift			1			1
inframe indel	7	3	2			12
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				4	9	13
Total	7	3	26	8	11

Highest pathogenic variant AF is 0.000331

Variants in PABPN1

This is a list of pathogenic ClinVar variants found in the PABPN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-23321469-G-T		Oculopharyngeal muscular dystrophy • PABPN1-related disorder	Uncertain significance (Sep 16, 2022)
14-23321471-TGGC-T		Oculopharyngeal muscular dystrophy	Uncertain significance (Sep 20, 2021)
14-23321471-T-TGGC		Oculopharyngeal muscular dystrophy • not specified	Conflicting classifications of pathogenicity (Jun 20, 2024)
14-23321471-T-TGGCGGC			Pathogenic (Apr 01, 2023)
14-23321471-T-TGGCGGCGGC		Oculopharyngeal muscular dystrophy 1 • Oculopharyngeal muscular dystrophy • Inborn genetic diseases	Pathogenic/Likely pathogenic (Feb 23, 2024)
14-23321471-T-TGGCGGCGGCGGCGGC		Oculopharyngeal muscular dystrophy	Pathogenic (Nov 01, 2022)
14-23321471-T-TGGCGGCGGCGGC		Oculopharyngeal muscular dystrophy • Oculopharyngeal muscular dystrophy 1	Pathogenic (Sep 20, 2024)
14-23321481-G-A			Likely benign (Nov 01, 2024)
14-23321481-G-GGCGGCGGCGGCA		Oculopharyngeal muscular dystrophy	Pathogenic/Likely pathogenic (Feb 01, 2024)
14-23321484-G-GGCGGCGGCA		Oculopharyngeal muscular dystrophy	Pathogenic/Likely pathogenic (Aug 08, 2023)
14-23321484-G-GGCGGCGGCAGCAGCA			Pathogenic (Aug 01, 2019)
14-23321486-C-T		Inborn genetic diseases	Uncertain significance (Feb 02, 2022)
14-23321487-G-GGCGGCA		Oculopharyngeal muscular dystrophy	Pathogenic (Aug 08, 2023)
14-23321490-G-GGCA		Oculopharyngeal muscular dystrophy • Oculopharyngeal muscular dystrophy 1	Conflicting classifications of pathogenicity (Jan 18, 2024)
14-23321490-G-GGCGGCGGCA			Pathogenic (Dec 01, 2018)
14-23321472-GGCGGCGGCGGCGGCGGCGGC-GGCGGCGGCGGCGGCGGCGGC		Oculopharyngeal muscular dystrophy 1	Pathogenic (Feb 01, 1998)
14-23321493-A-G			Uncertain significance (Nov 15, 2022)
14-23321495-C-T		Oculopharyngeal muscular dystrophy	Conflicting classifications of pathogenicity (May 01, 2023)
14-23321497-G-C		Inborn genetic diseases	Uncertain significance (Dec 14, 2021)
14-23321500-G-A		Oculopharyngeal muscular dystrophy	Conflicting classifications of pathogenicity (Apr 16, 2021)
14-23321504-G-C		Oculopharyngeal muscular dystrophy • PABPN1-related disorder • Oculopharyngeal muscular dystrophy 1	Uncertain significance (Jul 22, 2021)
14-23321506-G-C		Oculopharyngeal muscular dystrophy • Inborn genetic diseases	Uncertain significance (May 12, 2024)
14-23321507-C-A		Inborn genetic diseases	Uncertain significance (May 30, 2022)
14-23321515-G-T		Inborn genetic diseases	Uncertain significance (May 27, 2022)
14-23321521-G-T			Uncertain significance (Jun 07, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PABPN1	protein_coding	protein_coding	ENST00000216727	7	4897

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.392	0.606	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.81	89	152	0.587	0.00000935	1926
Missense in Polyphen		14	48.164	0.29067		511
Synonymous	-1.85	74	56.4	1.31	0.00000294	650
Loss of Function	2.67	3	13.6	0.220	8.64e-7	164

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). Stimulates poly(A) polymerase (PAPOLA) conferring processivity on the poly(A) tail elongation reaction and controls also the poly(A) tail length (By similarity). Increases the affinity of poly(A) polymerase for RNA (By similarity). 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 (PubMed:11371506). Binds to poly(A) and to poly(G) with high affinity (By similarity). May protect the poly(A) tail from degradation (By similarity). 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 (PubMed:27871484). {ECO:0000250|UniProtKB:Q28165, ECO:0000269|PubMed:11371506, ECO:0000269|PubMed:27871484}.
• Disease: DISEASE: Oculopharyngeal muscular dystrophy (OPMD) [MIM:164300]: A form of late-onset slowly progressive myopathy characterized by eyelid ptosis, dysphagia and, sometimes by other cranial and limb- muscle involvement. {ECO:0000269|PubMed:12673802}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Influenza A - Homo sapiens (human);mRNA surveillance pathway - Homo sapiens (human);mRNA Processing;Disease;Gene expression (Transcription);polyadenylation of mrna;NS1 Mediated Effects on Host Pathways;Host Interactions with Influenza Factors;Influenza Infection;RNA Polymerase II Transcription;Metabolism of RNA;Processing of Intronless Pre-mRNAs;Processing of Capped Intronless Pre-mRNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;Infectious disease;mRNA Splicing - Major Pathway;Inhibition of Host mRNA Processing and RNA Silencing;mRNA Splicing;mRNA 3,-end processing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.272

Haploinsufficiency Scores

• pHI: 0.0519
• hipred: Y
• hipred_score: 0.626
• ghis: 0.403

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.915

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pabpn1
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: MAPK cascade;mRNA splicing, via spliceosome;termination of RNA polymerase II transcription;RNA processing;muscle contraction;poly(A)+ mRNA export from nucleus;mRNA 3'-end processing;modification by virus of host mRNA processing;cellular response to lipopolysaccharide;positive regulation of polynucleotide adenylyltransferase activity
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear speck;nuclear inclusion body;ribonucleoprotein complex
• Molecular function: RNA binding;protein binding;RNA polymerase binding