PQBP1

Chr XXLR

polyglutamine binding protein 1

Also known as: MRX2, MRX55, MRXS3, MRXS8, NPW38, RENS1, SHS

NCBI Gene: 10084ENSG00000102103UniProt: O60828

This gene encodes a nuclear polyglutamine-binding protein that is involved with transcription activation. The encoded protein contains a WW domain. Mutations in this gene have been found in patients with Renpenning syndrome 1 and other syndromes with X-linked cognitive disability. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.[provided by RefSeq, Nov 2009]

Primary Disease Associations & Inheritance

Renpenning syndromeMIM #309500
XLR
0
Active trials
107
Pathogenic / LP
277
ClinVar variants
7
Pubs (1 yr)
1.9
Missense Z
0.50
LOEUF
Clinical Summary— PQBP1
🧬
Gene-Disease Validity (ClinGen)
Renpenning syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.79) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
107 Pathogenic / Likely Pathogenic· 109 VUS of 277 total submissions
📖
GeneReview available — PQBP1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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 OE0.11 (0.04–0.50)
0≤0.351.4
Missense OE0.52 (0.42–0.64)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 1 / 9.5Missense obs/exp: 65 / 125.5Syn Z: 0.23
LOF
DN
0.3594th %ile
GOF
0.4776th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 19% of P/LP variants are LoF · LOEUF 0.50

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

277 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic89
Likely Pathogenic18
VUS109
Likely Benign41
Benign10
Conflicting10
89
Pathogenic
18
Likely Pathogenic
109
VUS
41
Likely Benign
10
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
1
74
0
89
Likely Pathogenic
6
5
7
0
18
VUS
4
80
22
3
109
Likely Benign
0
5
16
20
41
Benign
0
0
5
5
10
Conflicting
—10
Total249112428277

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

PQBP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PQBP1-related Renpenning syndrome

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients