HNRNPR

Chr 1AD

heterogeneous nuclear ribonucleoprotein R

Also known as: HNRPR, NEDDFSB, hnRNP-R

This gene encodes an RNA-binding protein that is a component of the spliceosome C complex and functions in pre-mRNA processing within ribonucleoprotein complexes. Mutations cause a neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.21), indicating that heterozygous variants are likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.211 OMIM phenotype
Clinical SummaryHNRNPR
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.21LOEUF
pLI 0.999
Z-score 4.74
OE 0.07 (0.030.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.54Z-score
OE missense 0.48 (0.420.54)
174 obs / 364.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.07 (0.030.21)
00.351.4
Missense OE0.48 (0.420.54)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 2 / 30.0Missense obs/exp: 174 / 364.0Syn Z: 0.93
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHNRNPR-related intellectual disabilityLOFAD
DN
0.3097th %ile
GOF
0.3590th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.21

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HNRNPR · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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