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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GRSF1
G-rich RNA sequence binding factor 1
Chromosome 4 · 4q13.3
NCBI Gene: 2926Ensembl: ENSG00000132463.16HGNC: HGNC:4610UniProt: Q12849
120PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingribonucleoprotein granulemitochondrial nucleoidmRNA bindingneurodegenerative diseaseinfluenzatype 2 diabetes mellituslung adenocarcinoma
✦AI Summary

GRSF1 is an RNA-binding protein that primarily functions as a regulator of post-transcriptional gene expression in mitochondria and the nucleus. In mitochondria, GRSF1 binds G-rich RNA sequences and is required for mitochondrial ribosome assembly and recruitment of mRNAs and long non-coding RNAs, particularly ND6 mRNA and transcripts from the light strand of mtDNA 123. GRSF1 facilitates degradosome-mediated decay of non-coding mitochondrial transcripts by unwinding G-quadruplex RNA structures, enabling their degradation 3. Beyond mitochondrial function, GRSF1 regulates post-transcriptional stability of nuclear-encoded mRNAs. It stabilizes BCKDHB mRNA by directly binding G-tracts in its coding region, maintaining branched-chain amino acid homeostasis critical for cardiac function 4. GRSF1 also negatively regulates fibrinogen mRNA stability, antagonizing age-associated hypercoagulability 5. Additionally, GRSF1 controls nuclear export and translation of mitochondrial long non-coding RNA RMRP and influenza A virus nucleoprotein mRNAs 67. Clinically, GRSF1 downregulation is implicated in heart failure pathogenesis and cellular senescence. Loss of GRSF1 causes mitochondrial stress, increased ROS production, DNA damage, and pro-inflammatory responses 8. GRSF1 has been identified as a candidate disease gene in clinical genomics 9, and super-resolution microscopy techniques now enable visualization of GRSF1-associated mitochondrial mRNA distribution in health and disease states 10.

Sources cited
1
In mitochondria, GRSF1 binds G-rich RNA sequences and is required for mitochondrial ribosome assembly and recruitment of mRNAs and long non-coding RNAs, particularly ND6 mRNA and transcripts from the light strand of mtDNA , , .
PMID: 29967381
2
It stabilizes BCKDHB mRNA by directly binding G-tracts in its coding region, maintaining branched-chain amino acid homeostasis critical for cardiac function .
PMID: 41487100
3
GRSF1 also negatively regulates fibrinogen mRNA stability, antagonizing age-associated hypercoagulability .
PMID: 37923734
4
Loss of GRSF1 causes mitochondrial stress, increased ROS production, DNA damage, and pro-inflammatory responses .
PMID: 30086537
5
GRSF1 has been identified as a candidate disease gene in clinical genomics , and super-resolution microscopy techniques now enable visualization of GRSF1-associated mitochondrial mRNA distribution in health and disease states .
PMID: 28600779
6
GRSF1 has been identified as a candidate disease gene in clinical genomics , and super-resolution microscopy techniques now enable visualization of GRSF1-associated mitochondrial mRNA distribution in health and disease states .
PMID: 40640125
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.51Moderate
influenzaOpen Targets
0.37Weak
type 2 diabetes mellitusOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
SepsisOpen Targets
0.07Suggestive
response to statinOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
transient myeloproliferative syndromeOpen Targets
0.05Suggestive
subarachnoid hemorrhageOpen Targets
0.05Suggestive
pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9Open Targets
0.04Suggestive
cervical cancerOpen Targets
0.04Suggestive
reticular dysgenesisOpen Targets
0.03Suggestive
atrial fibrillationOpen Targets
0.03Suggestive
thrombophiliaOpen Targets
0.03Suggestive
heart failureOpen Targets
0.03Suggestive
triple-negative breast cancerOpen Targets
0.03Suggestive
Duodenal AdenocarcinomaOpen Targets
0.03Suggestive
lung cancerOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GPX4Protein interaction96%DHX30Protein interaction83%FASTKD2Protein interaction83%SUPV3L1Protein interaction82%DDX28Protein interaction79%TRMT10CProtein interaction79%
Tissue Expression6 tissues
Heart
100%
Brain
87%
Liver
47%
Lung
43%
Ovary
39%
Bone Marrow
34%
Gene Interaction Network
Click a node to explore
GRSF1GPX4DHX30FASTKD2SUPV3L1DDX28TRMT10C
PROTEIN STRUCTURE
Preparing viewer…
PDB4QU6 · 1.75 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.47LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.06 [0.78–1.47]
RankingsWhere GRSF1 stands among ~20K protein-coding genes
  • #3,919of 20,598
    Most Researched120 · top quartile
  • #14,991of 17,882
    Most Constrained (LOEUF)1.47
Genes detectedGRSF1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
GRSF1 Protects Against Heart Failure by Maintaining BCAA Homeostasis.
PMID: 41487100
Circulation · 2026
1.00
2
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
PMID: 28600779
Hum Genet · 2017
0.90
3
Super-resolution microscopy of mitochondrial mRNAs.
PMID: 40640125
Nat Commun · 2025
0.80
4
The HNRNPF/H RNA binding proteins and disease.
PMID: 37042074
Wiley Interdiscip Rev RNA · 2023
0.70
5
HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP.
PMID: 27198227
Genes Dev · 2016
0.60