HNRNPR

Chr 1AD

heterogeneous nuclear ribonucleoprotein R

Also known as: HNRPR, NEDDFSB, hnRNP-R

NCBI Gene: 10236ENSG00000125944UniProt: O43390

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]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalitiesMIM #620073
AD
109
ClinVar variants
12
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
Clinical Summary— HNRNPR
⚡
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.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 73 VUS of 109 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.48 (0.42–0.54)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 2 / 30.0Missense obs/exp: 174 / 364.0Syn Z: 0.93

ClinVar Variant Classifications

109 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS73
Likely Benign8
9
Pathogenic
3
Likely Pathogenic
73
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
4
0
9
Likely Pathogenic
0
1
2
0
3
VUS
3
63
7
0
73
Likely Benign
0
6
1
1
8
Benign
0
0
0
0
0
Total77114193

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

View 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.

Gene2Phenotype Curations

HNRNPR-related intellectual disability

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities

MIM #620073

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders.
Gillentine MA et al.·Genome Med
2021
HNRNPA2B1 and HNRNPR stabilize ASCL1 in an m6A-dependent manner to promote neuroblastoma progression.
Hu T et al.·Biochim Biophys Acta Mol Basis Dis
2024
Targeting SKAP2 restores sperm motility and morphology through modulating mitochondrial organization and cytoskeletal remodeling.
Gan S et al.·Signal Transduct Target Ther
2025Functional
HnRNPR-mediated UPF3B mRNA splicing drives hepatocellular carcinoma metastasis.
Wang H et al.·J Adv Res
2025
Pan-cancer analysis of the oncogenic role of HNRNPR in human tumors.
Yang Y et al.·Cell Biol Int
2023
High expression of HNRNPR in ESCA combined with (18)F-FDG PET/CT metabolic parameters are novel biomarkers for preoperative diagnosis of ESCA.
Liu XY et al.·J Transl Med
2022
HNRNPR Variants that Impair Homeobox Gene Expression Drive Developmental Disorders in Humans.
Duijkers FA et al.·Am J Hum Genet
2019
Prognostic implication of six m6A-modulated genes signature in the ferroptosis for hepatocellular carcinoma patients.
He Y et al.·Clin Exp Med
2025Cohort
Sporadic Amyotrophic Lateral Sclerosis Skeletal Muscle Transcriptome Analysis: A Comprehensive Examination of Differentially Expressed Genes.
Gascón E et al.·Biomolecules
2024Review
JUN-induced super-enhancer RNA forms R-loop to promote nasopharyngeal carcinoma metastasis.
Jia Q et al.·Cell Death Dis
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Neurodevelopmental DisordersIntellectual DisabilityDevelopmental Delay

Longitudinal Study of Neurogenetic Disorders

RECRUITING
NCT03492060Columbia UniversityStarted 2018-06-13
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools