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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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LRRFIP1
LRR binding FLII interacting protein 1
Chromosome 2 · 2q37.3
NCBI Gene: 9208Ensembl: ENSG00000124831.21HGNC: HGNC:6702UniProt: A0A0F7NGI8
105PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA polymerase II cis-regulatory region sequence-specific DNA bindingprotein bindingprotein homodimerization activitycadherin bindingcanceratrial fibrillationmyelodysplastic syndromechronic myelogenous leukemia
✦AI Summary

LRRFIP1 (Leucine Rich Repeat of Flightless-1 Interacting Protein 1) is a multifunctional transcriptional repressor that regulates diverse biological processes through sequence-specific DNA binding and protein interactions. The protein preferentially binds to GC-rich consensus sequences and functions as a transcriptional repressor of genes including EGFR and PDGFA 1. LRRFIP1 also binds double-stranded RNA and positively regulates Toll-like receptor signaling by competing with negative regulators for MYD88 binding 12. Mechanistically, LRRFIP1 undergoes serine phosphorylation in response to immunologic stimuli and localizes to lysosomal structures containing dsRNA 2. The protein inhibits the NLRP1 inflammasome and regulates hematopoiesis through the ZAKα/P38 kinase pathway 3. In metabolic regulation, LRRFIP1 inhibits white adipocyte differentiation by suppressing the E2F6/C/EBPα axis 4. Disease relevance includes associations with glioma prognosis where high expression correlates with poor outcomes 5, genetic variants linked to adiposity and inflammation 6, and involvement in myelodysplastic syndrome through Wnt/β-catenin pathway enhancement 7. LRRFIP1 represents a promising therapeutic target for metabolic disorders, inflammatory diseases, and certain cancers.

Sources cited
1
LRRFIP1 is a transcriptional repressor that binds GC-rich sequences and regulates EGFR/PDGFA, also binds dsRNA and regulates TLR signaling
PMID: 30709060
2
LRRFIP1 undergoes serine phosphorylation in response to stimuli and localizes to lysosomal structures with dsRNA
PMID: 21102652
3
LRRFIP1 inhibits NLRP1 inflammasome and regulates hematopoiesis through ZAKα/P38 kinase pathway
PMID: 37675820
4
LRRFIP1 inhibits white adipocyte differentiation by suppressing E2F6/C/EBPα axis
PMID: 41224206
5
LRRFIP1 expression is associated with poor prognosis in glioma patients
PMID: 35338570
6
Genetic variants in LRRFIP1 are associated with abdominal adiposity and inflammation markers
PMID: 23505185
7
LRRFIP1 enhances Wnt/β-catenin pathway in myelodysplastic syndrome
PMID: 40420163
Disease Associationsⓘ20
cancerOpen Targets
0.60Moderate
atrial fibrillationOpen Targets
0.45Moderate
myelodysplastic syndromeOpen Targets
0.39Weak
chronic myelogenous leukemiaOpen Targets
0.37Weak
acute lymphoblastic leukemiaOpen Targets
0.37Weak
leukemiaOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.36Weak
oropharynx cancerOpen Targets
0.31Weak
Peyronie diseaseOpen Targets
0.28Weak
systemic inflammatory response syndromeOpen Targets
0.24Weak
myoepithelial tumorOpen Targets
0.11Weak
Self-injurious behaviorOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
cesarean sectionOpen Targets
0.10Weak
gliomaOpen Targets
0.08Suggestive
rheumatoid arthritisOpen Targets
0.07Suggestive
obesityOpen Targets
0.05Suggestive
hepatitis C virus infectionOpen Targets
0.05Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CTNNB1Protein interaction97%FLIIProtein interaction85%GCFC2Protein interaction85%MYD88Protein interaction81%TMOD1Protein interaction78%DHX36Protein interaction74%
Tissue Expression6 tissues
Lung
100%
Heart
76%
Bone Marrow
55%
Brain
52%
Liver
43%
Ovary
20%
Gene Interaction Network
Click a node to explore
LRRFIP1CTNNB1FLIIGCFC2MYD88TMOD1DHX36
PROTEIN STRUCTURE
Preparing viewer…
PDB4H22 · 2.89 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.62 [0.47–0.81]
RankingsWhere LRRFIP1 stands among ~20K protein-coding genes
  • #4,538of 20,598
    Most Researched105 · top quartile
  • #6,843of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedLRRFIP1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Multidisciplinary Roles of LRRFIP1/GCF2 in Human Biological Systems and Diseases.
PMID: 30709060
Cells · 2019
1.00
2
LRRFIP1, an epigenetically regulated gene, is a prognostic biomarker and predicts malignant phenotypes of glioma.
PMID: 35338570
CNS Neurosci Ther · 2022
0.90
3
A variant in the LRRFIP1 gene is associated with adiposity and inflammation.
PMID: 23505185
Obesity (Silver Spring) · 2013
0.80
4
Characterization of LRRFIP1.
PMID: 21102652
Biochem Cell Biol · 2010
0.70
5
ZAKα/P38 kinase signaling pathway regulates hematopoiesis by activating the NLRP1 inflammasome.
PMID: 37675820
EMBO Mol Med · 2023
0.60