HNRNPR

Chr 1

heterogeneous nuclear ribonucleoprotein R

Also known as: HNRPR, NEDDFSB, hnRNP-R

NCBI Gene: 10236 ENSG00000125944 UniProt: O43390

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an RNA-binding protein that is a member of the spliceosome C complex, which functions in pre-mRNA processing and transport. The encoded protein also promotes transcription at the c-fos gene. Alternative splicing results in multiple transcript variants. There are pseudogenes for this gene on chromosomes 4, 11, and 10. [provided by RefSeq, Jul 2014]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.21

Clinical Summary— HNRNPR

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Gene-Disease Validity (ClinGen)

syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 73 VUS of 106 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.21LOEUF

pLI 0.999

Z-score 4.74

OE 0.07 (0.03–0.21)

Highly constrained

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

Missense Constraint?

3.54Z-score

OE missense 0.48 (0.42–0.54)

174 obs / 364.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.21)

0≤0.351.4

Missense OE?0.48 (0.42–0.54)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 2 / 30.0Missense obs/exp: 174 / 364.0Syn Z: 0.93

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveHNRNPR-related intellectual disabilityLOFAD

This gene — mechanism propensity

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 · 75% of P/LP variants are LoF · 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

106 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic3

VUS73

Likely Benign9

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	1	0	0	5
Likely Pathogenic	2	1	0	0	3
VUS	5	67	1	0	73
Likely Benign	0	7	1	1	9
Benign	0	0	0	0	0
Total	11	76	2	1	90

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

View in ClinVar →

4 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap HNRNPR — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →