PABPN1

protein-coding

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

Gene summary

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. [provided by RefSeq, Dec 2010]

Previous symbols:

OPMD
PABP2

MANE transcript

NM_004643.4

Inheritance

AD, AR

ClinVar variants

P:1U:54B:12

Top phenotype

Oculopharyngeal muscular dystrophy 1

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr14:23,321,457-23,326,163

External References & Databases

Ensembl (ENSG00000100836)

Transcript & Mutation Effects

hg38 • Region Span ~4.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oculopharyngeal muscular dystrophy 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0958176

Submitter: PanelApp Australia

oculopharyngeal muscular dystrophy 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0958176

Submitter: PanelApp Australia

oculopharyngeal muscular dystrophyDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008116

Submitter: Ambry Genetics

oculopharyngeal muscular dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008116

Submitter: Orphanet

oculopharyngeal muscular dystrophySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008116

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Oculopharyngeal muscular dystrophy 1AD/AR

Manifestation: Musculoskeletal

Intervention: General

Rationale: 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

Refs: 13997067; 13963574; 9462747; 11712939; 15725589; 15694141; 16648376; 20301305; 21647273; 21742497; 21956377; 22817818

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PABPN1 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 35

not providedTotal: 34

Oculopharyngeal muscular dystrophy 1Total: 28

not specifiedTotal: 10

PABPN1-related disordersTotal: 7

Oculopharyngeal muscular dystrophyTotal: 5

PABPN1-related disorderTotal: 3

BCL2L2-PABPN1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004643.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	8 clinvar	1 clinvar	11
missense		1 clinvar	50 clinvar	3 clinvar		54
nonsense						0
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	1	54	11	1	67

Highest pathogenic variant AF is 0.000032017444

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004643.4	RefSeq	NP_004634.1	7	MANE Select
ENST00000216727.9	Ensembl	ENSP00000216727.4	7	MANE Select
NM_001360551.3	RefSeq	NP_001347480.1	6	Standard
NM_001360552.2	RefSeq	NP_001347481.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Influenza A - Homo sapiens (human)
mRNA surveillance pathway - Homo sapiens (human)
mRNA Processing
Disease
Gene expression (Transcription)

Biological Process

MAPK cascade
mRNA splicing, via spliceosome
termination of RNA polymerase II transcription
RNA processing
muscle contraction

Molecular Function

RNA binding
protein binding
RNA polymerase binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
nuclear speck
nuclear inclusion body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216727
Coding exons: 7
Length: 4897
Individuals with no LoFs: 125744
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125748
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.81	89	152	0.587	0.00000935	1926
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.272

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.915

Gene Damage Prediction

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