PQBP1

Chr XXLR

polyglutamine binding protein 1

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

NCBI Gene: 10084 ENSG00000102103 UniProt: O60828 OMIM: 300463

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismXLRLOEUF 0.501 OMIM phenotype

Clinical Summary— PQBP1

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Gene-Disease Validity (ClinGen)

Renpenning syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.79) — some intolerance to loss-of-function variants.

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ClinVar Variants

36 unique Pathogenic / Likely Pathogenic· 101 VUS of 232 total submissions

Explore recent and relevant literature in Research Assistant →

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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 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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePQBP1-related Renpenning syndromeLOFXLR

This gene — mechanism propensity

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 · 75% of P/LP variants are LoF · LOEUF 0.50 · ClinGen HI: Sufficient evidence for dosage pathogenicity

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

232 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19

Likely Pathogenic17

VUS101

Likely Benign38

Benign10

Conflicting10

Pathogenic

Likely Pathogenic

101

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	2	1	0	19
Likely Pathogenic	11	6	0	0	17
VUS	4	85	9	3	101
Likely Benign	0	5	15	18	38
Benign	0	0	5	5	10
Conflicting	—				10
Total	31	98	30	26	195

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

View in ClinVar →

77 pathogenic / likely-pathogenic (of 87) ClinVar copy-number / structural variants overlap PQBP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →