PQBP1

Chr X

polyglutamine binding protein 1

This gene encodes a nuclear polyglutamine-binding protein that functions as a scaffold protein involved in pre-mRNA splicing, transcription regulation, and neuron development. Mutations cause Renpenning syndrome, an X-linked recessive intellectual disability disorder. The gene has a GeneReviews entry providing detailed clinical information for affected families.

ResearchSummary from RefSeq, OMIM, UniProt

Intrinsically disordered protein that acts as a scaffold, and which is involved in different processes, such as pre-mRNA splicing, transcription regulation, innate immunity and neuron development (PubMed:10198427, PubMed:10332029, PubMed:12062018, PubMed:20410308, PubMed:23512658). Interacts with splicing-related factors via the intrinsically disordered region and regulates alternative splicing of target pre-mRNA species (PubMed:10332029, PubMed:12062018, PubMed:20410308, PubMed:23512658). May suppress the ability of POU3F2 to transactivate the DRD1 gene in a POU3F2 dependent manner. Can activate transcription directly or via association with the transcription machinery (PubMed:10198427). May be involved in ATXN1 mutant-induced cell death (PubMed:12062018). The interaction with ATXN1 mutant reduces levels of phosphorylated RNA polymerase II large subunit (PubMed:12062018). Involved in the assembly of cytoplasmic stress granule, possibly by participating in the transport of neuronal RNA granules (PubMed:21933836). Also acts as an innate immune sensor of infection by retroviruses, such as HIV, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:26046437). Directly binds retroviral reverse-transcribed DNA in the cytosol and interacts with CGAS, leading to activate the cGAS-STING signaling pathway, triggering type-I interferon production (PubMed:26046437)

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtRenpenning syndrome 1

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Renpenning syndrome · XL · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.789

Z-score 2.56

OE 0.11 (0.04–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.92Z-score

OE missense 0.52 (0.42–0.64)

65 obs / 125.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.50)

0≤0.351.4

Missense OE?0.52 (0.42–0.64)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 1 / 9.5Missense obs/exp: 65 / 125.5Syn Z: 0.23

Background carrier burden — how many people carry a rare variant somewhere in PQBP1?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 680

175 rare PASS variants

Rare truncating (LoF)

1 in 49,000

8 rare PASS variants

Rare synonymous (reference)

1 in 470

90 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PQBP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓