HNRNPD: Heterogeneous Nuclear Ribonucleoprotein D
A multifunctional RNA-binding protein involved in mRNA stability, splicing, and transcriptional regulation, with roles in cancer and autoimmune disease.
Gene Information Card
| Symbol | HNRNPD |
|---|---|
| Full Name | heterogeneous nuclear ribonucleoprotein D |
| Gene Type | protein-coding |
| Chromosomal Location | 4q21.22 |
| NCBI Gene ID | 3184 ncbi.nlm.nih.gov/gene/3184 |
| Ensembl ID | ENSG00000138668 |
| UniProt ID | Q14103 |
| OMIM ID | 601324 |
| HGNC ID | 5036 |
| Aliases | AUF1, hnRNPD0, P37, AUF1A, AUF1B, AUF1C, AUF1D |
Description
The HNRNPD gene encodes heterogeneous nuclear ribonucleoprotein D (also known as AUF1), a member of the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). This protein binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs, regulating their stability and translation. HNRNPD is involved in multiple cellular processes including mRNA decay, splicing, transcriptional regulation, and telomere maintenance. Alternative splicing generates multiple isoforms with distinct functions. Dysregulation of HNRNPD has been implicated in cancer, autoimmune disorders, and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | HNRNPD overexpression stabilizes oncogenic mRNAs (e.g., cyclin D1, c-Myc) promoting cell proliferation | PMID: 21947295 |
| Colorectal cancer | Altered HNRNPD expression correlates with poor prognosis and metastasis | PMID: 25605247 |
| Systemic lupus erythematosus | HNRNPD autoantibodies detected in patient sera; protein involved in mRNA processing of immune-related genes | PMID: 10891526 |
| Rheumatoid arthritis | HNRNPD regulates stability of pro-inflammatory cytokine mRNAs (e.g., TNF-α) | PMID: 14525967 |
| Prostate cancer | HNRNPD loss-of-function mutations associated with aggressive disease | PMID: 27197191 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 28.5 | High |
| Spleen | 25.3 | High |
| Bone marrow | 22.1 | High |
| Lung | 18.7 | Medium |
| Breast | 15.2 | Medium |
| Colon | 12.8 | Medium |
| Brain | 8.4 | Low |
| Heart | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 32.4 | Cervical carcinoma; high expression |
| K562 | 29.1 | Leukemia; high expression |
| A549 | 24.7 | Lung carcinoma; high expression |
| MCF7 | 21.3 | Breast carcinoma; medium expression |
| HEK293 | 18.9 | Embryonic kidney; medium expression |
| HepG2 | 15.6 | Hepatocellular carcinoma; medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; likely loss of function |
| c.214C>T (p.Arg72Trp) | Missense | 0.01% | Altered RNA-binding affinity; associated with autoimmune disease |
| c.487G>A (p.Gly163Arg) | Missense | 0.005% | Reduced protein stability; reported in cancer |
| c.742_743insA (p.Thr248Asnfs*5) | Frameshift | 0.001% | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., c.742_743insA) that truncate the protein or disrupt RNA-binding domains lead to loss of mRNA destabilization activity.
Gain of Function (GOF)
Missense mutations (e.g., c.214C>T) that enhance binding to ARE-containing mRNAs may increase stability of oncogenic transcripts, contributing to tumorigenesis.
Dominant Negative (DN)
Mutations that produce truncated isoforms capable of dimerizing with wild-type HNRNPD but lacking functional domains can interfere with normal mRNA decay.
View complete mutation data：
Gene Ontology (GO)
Pathways
• mRNA surveillance pathway (Reactome: R-HSA-72163)
• AUF1 (hnRNP D0) binds and destabilizes mRNA (Reactome: R-HSA-450408)
• Regulation of mRNA stability by proteins that bind AU-rich elements (KEGG: hsa03018)
• Apoptosis (KEGG: hsa04210) - indirect via BCL2 mRNA regulation
Protein Summary
HNRNPD (AUF1) is a 37-40 kDa RNA-binding protein that shuttles between nucleus and cytoplasm. It contains two N-terminal RNA recognition motifs (RRMs) and a C-terminal glycine-rich domain. The protein binds to AU-rich elements in the 3'-UTR of target mRNAs, recruiting the exosome complex to promote mRNA decay. Four major isoforms (p37, p40, p42, p45) arise from alternative splicing, with distinct tissue distributions and functions. HNRNPD also participates in telomere maintenance by binding to telomeric DNA and regulating telomerase activity. Post-translational modifications including phosphorylation and ubiquitination modulate its stability and RNA-binding affinity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HNRNPD Knockout HEK293 Cell Line | EDJ-KQ4903 | Human | 3184 | Details Get a Quote |
| HNRNPDL Knockout HEK293 Cell Line | EDJ-KQ6856 | Human | 9987 | Details Get a Quote |
| HNRNPDL Knockout HeLa Cell Line | EDJ-KQ30059 | Human | 9987 | Details Get a Quote |
| HNRNPD Knockout A-549 Cell Line | EDJ-KQ27724 | Human | 3184 | Details Get a Quote |
| HNRNPD Knockout HCT 116 Cell Line | EDJ-KQ27725 | Human | 3184 | Details Get a Quote |
| HNRNPD Knockout HeLa Cell Line | EDJ-KQ27726 | Human | 3184 | Details Get a Quote |
| HNRNPDL Knockout A-549 Cell Line | EDJ-KQ31430 | Human | 9987 | Details Get a Quote |
| HNRNPDL Knockout HCT 116 Cell Line | EDJ-KQ31431 | Human | 9987 | Details Get a Quote |
