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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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HNRNPR
heterogeneous nuclear ribonucleoprotein R
Chromosome 1 Β· 1p36.12
NCBI Gene: 10236Ensembl: ENSG00000125944.22HGNC: HGNC:5047UniProt: A0A6Q8PEX7
306PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleolusRNA bindingprotein bindingnucleusneurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalitiesIntellectual disabilityGlobal developmental delaySecondary microcephaly
✦AI Summary

HNRNPR (heterogeneous nuclear ribonucleoprotein R) is a component of ribonucleosomes that plays critical roles in RNA processing and splicing. As a member of the hnRNP family, HNRNPR functions in precursor mRNA processing through RNA binding and spliceosomal complex participation 1. Beyond canonical splicing, HNRNPR regulates gene expression through m6A-dependent mechanisms: it stabilizes ASCL1 mRNA in neuroblastoma by binding to its untranslated regions in an m6A-dependent manner 2, protects XB130 mRNA from exonuclease degradation in lung cancer 3, and mediates UPF3B alternative splicing in hepatocellular carcinoma 4. Clinically, HNRNPR mutations cause neurodevelopmental disorders with dysmorphic facies and skeletal/brain abnormalities, with enriched de novo variants identified across 188-221 NDD probands showing radial glial expression patterns critical for cerebral cortical development 1. Additionally, HNRNPR mutations cause male infertility through disrupted m6A-dependent splicing of spermiogenesis genes (SKAP2, PLCZ1), affecting sperm motility and morphology 56. In cancer, HNRNPR is frequently overexpressed and associated with poor prognosis, particularly in hepatocellular carcinoma and lung adenocarcinoma, where it promotes tumor progression through EMT activation and immune modulation 7. These findings establish HNRNPR as a multifunctional regulator with pathogenic roles in neurodevelopment, fertility, and oncology.

Sources cited
1
HNRNPR is one of five hnRNP genes implicated in neurodevelopmental disorders with enriched de novo variants; shows radial glial expression critical for cerebral cortical development
PMID: 33874999
2
HNRNPR mutations cause male infertility by disrupting m6A-dependent splicing of SKAP2, impairing sperm motility and morphology
PMID: 41436426
3
HNRNPR mutations cause oocyte activation failure through impaired m6A-dependent PLCZ1 splicing, with artificial oocyte activation and PLCΞΆ restoration as therapeutic strategies
PMID: 41618099
4
HNRNPR stabilizes ASCL1 mRNA in m6A-dependent manner in neuroblastoma by binding to 3'UTR; promotes neuroblastoma cell growth and invasion
PMID: 38331110
5
HNRNPR promotes NSCLC progression by protecting XB130 mRNA from XRN1- and DIS3L2-mediated degradation, activating EMT and Akt signaling
PMID: 40268079
6
HNRNPR mediates UPF3B alternative splicing via RRM2 domain to generate oncogenic UPF3B-S variant, driving HCC metastasis through CDH1 mRNA degradation and YAP1-Hippo signaling
PMID: 38402949
7
Pan-cancer analysis shows HNRNPR overexpression associated with poor prognosis especially in hepatocellular carcinoma; correlates with immune cell infiltration and tumor mutation burden
PMID: 37077028
Disease Associationsβ“˜21
neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalitiesOpen Targets
0.69Moderate
Intellectual disabilityOpen Targets
0.55Moderate
Global developmental delayOpen Targets
0.46Moderate
Secondary microcephalyOpen Targets
0.46Moderate
SeizureOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.45Moderate
neurodegenerative diseaseOpen Targets
0.37Weak
dengue diseaseOpen Targets
0.37Weak
syndromic intellectual disabilityOpen Targets
0.37Weak
gastric cancerOpen Targets
0.08Suggestive
Pick diseaseOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
Blackfan-Diamond anemiaOpen Targets
0.07Suggestive
FRAXF syndromeOpen Targets
0.06Suggestive
mosaic variegated aneuploidy syndrome 4Open Targets
0.05Suggestive
primary familial polycythemia due to EPO receptor mutationOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
Alpha-thalassemia - myelodysplastic syndromeOpen Targets
0.05Suggestive
alpha-thalassemia-myelodysplastic syndromeOpen Targets
0.05Suggestive
neutrophil immunodeficiency syndromeOpen Targets
0.05Suggestive
Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalitiesUniProt
Pathogenic Variants8
NM_005826.5(HNRNPR):c.455C>A (p.Pro152Gln)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 152
NM_005826.5(HNRNPR):c.332_333del (p.Gln111fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 111
NM_005826.5(HNRNPR):c.1599_1600dup (p.Ala534fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2023β†’ Residue 534
NM_005826.5(HNRNPR):c.1651C>T (p.Gln551Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 551
NM_005826.5(HNRNPR):c.1654C>T (p.Gln552Ter)Likely pathogenic
Inborn genetic diseases|Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities
β˜…β˜†β˜†β˜†2015β†’ Residue 552
NM_005826.5(HNRNPR):c.1754G>A (p.Arg585His)Pathogenic
Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities
β˜†β˜†β˜†β˜†2023β†’ Residue 585
NM_005826.5(HNRNPR):c.1643dup (p.Pro549fs)Pathogenic
Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities
β˜†β˜†β˜†β˜†2022β†’ Residue 549
NM_005826.5(HNRNPR):c.1600dup (p.Ala534fs)Pathogenic
Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities
β˜†β˜†β˜†β˜†2022β†’ Residue 534
View on ClinVar β†—
Related Genes
GPATCH1Shared pathway100%SNRPFProtein interaction100%SNRNP70Protein interaction100%SRSF1Protein interaction96%FUSProtein interaction96%HNRNPA1Protein interaction96%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
89%
Ovary
65%
Heart
57%
Lung
52%
Liver
35%
Gene Interaction Network
Click a node to explore
HNRNPRGPATCH1SNRPFSNRNP70SRSF1FUSHNRNPA1
PROTEIN STRUCTURE
Preparing viewer…
PDB9EJY Β· 1.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.13Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.04 [0.02–0.13]
RankingsWhere HNRNPR stands among ~20K protein-coding genes
  • #1,128of 20,598
    Most Researched306 Β· top 10%
  • #3,020of 5,498
    Most Pathogenic Variants8
  • #136of 17,882
    Most Constrained (LOEUF)0.13 Β· top 1%
Genes detectedHNRNPR
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders.
PMID: 33874999
Genome Med Β· 2021
1.00
2
Targeting SKAP2 restores sperm motility and morphology through modulating mitochondrial organization and cytoskeletal remodeling.
PMID: 41436426
Signal Transduct Target Ther Β· 2025
0.90
3
Characterization and therapy of fertilization failure in murine and human models with HNRNPR mutations.
PMID: 41618099
EMBO Mol Med Β· 2026
0.80
4
HNRNPA2B1 and HNRNPR stabilize ASCL1 in an m6A-dependent manner to promote neuroblastoma progression.
PMID: 38331110
Biochim Biophys Acta Mol Basis Dis Β· 2024
0.70
5
HNRNPR Variants that Impair Homeobox Gene Expression Drive Developmental Disorders in Humans.
PMID: 31079900
Am J Hum Genet Β· 2019
0.68