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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FAF2
Fas associated factor family member 2
Chromosome 5 · 5q35.2
NCBI Gene: 23197Ensembl: ENSG00000113194.14HGNC: HGNC:24666UniProt: Q96CS3
211PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
lipid droplet organizationprotein bindingprotein-macromolecule adaptor activityubiquitin protein ligase bindingneurodegenerative diseaseessential hypertensionchronic musculoskeletal painhypertension
✦AI Summary

FAF2 (Fas-associated factor family member 2) is a bifunctional ubiquitin-regulatory adaptor protein with diverse roles in protein quality control and organellar homeostasis. Structurally, FAF2 functions as a VCP/p97 cofactor through its UBX domain to facilitate ubiquitin-dependent protein extraction and degradation 12. Primarily, FAF2 mediates endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins and regulates stress granule disassembly by promoting ubiquitinated G3BP1 extraction via VCP engagement 1. FAF2 maintains peroxisomal homeostasis by extracting ubiquitylated peroxisomal membrane proteins like PMP70, thereby preventing excessive pexophagy under steady-state conditions 23. Metabolically, FAF2 inhibits lipid droplet degradation through PNPL2 inhibition and regulates saturated fatty acid responses via peroxisomal ether lipid synthesis 45. FAF2 also modulates cholesterol-dependent mTORC1 signaling through ER-lysosome contacts 6. Clinically relevant, FAF2 elevation associates with alcohol-associated liver disease; its knockdown reduces hepatic steatosis by enhancing lipolysis and upregulating PCSK9 pathways 7. Additionally, targeted FAF2 delivery suppresses tau aggregation and ameliorates neurodegeneration in tau pathology models 8, suggesting therapeutic potential in metabolic and neurodegenerative diseases.

Sources cited
1
FAF2 associates with ubiquitinated G3BP1 and promotes its interaction with VCP to facilitate stress granule disassembly
PMID: 34739333
2
FAF2 maintains peroxisomal homeostasis by modulating turnover of peroxisomal membrane proteins and preventing pexophagy
PMID: 39472561
3
FAF2/UBXD8 and p97 work together to maintain peroxisome abundance by preventing pexophagy through ubiquitylated protein extraction
PMID: 40728716
4
Cholesterol binds ER-anchored FAF2 to promote mTOR complex formation and activation at ER-lysosome contacts
PMID: 35995997
5
FAF2 is a bifunctional regulator of peroxisomal protein abundance and saturated fatty acid-induced cellular stress responses
PMID: 39763943
6
FAF2 regulates peroxisomal abundance and function in response to saturated fatty acids through UBX domain requirements
PMID: 40601736
7
FAF2 knockdown mitigates alcohol-induced liver steatosis by enhancing lipolysis and modulating SREBP1 and PCSK9 pathways
PMID: 39969435
8
Targeted FAF2/UBXD8 suppresses tau aggregation independent of VCP and reduces tau pathology in mouse models
PMID: 40902597
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.44Moderate
essential hypertensionOpen Targets
0.27Weak
chronic musculoskeletal painOpen Targets
0.27Weak
hypertensionOpen Targets
0.27Weak
Hepatic steatosisOpen Targets
0.03Suggestive
steatosisOpen Targets
0.02Suggestive
infectionOpen Targets
0.02Suggestive
nasopharyngeal carcinomaOpen Targets
0.01Suggestive
viral diseaseOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
COVID-19Open Targets
0.01Suggestive
tauopathyOpen Targets
0.01Suggestive
atopic eczemaOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.01Suggestive
ataxia telangiectasiaOpen Targets
0.01Suggestive
amyotrophic lateral sclerosisOpen Targets
0.01Suggestive
arthritisOpen Targets
0.01Suggestive
lung cancerOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
AMFRProtein interaction100%CANXProtein interaction100%P4HBProtein interaction100%UBE2G2Protein interaction100%EDEM1Protein interaction100%OS9Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
80%
Liver
77%
Ovary
70%
Heart
61%
Lung
60%
Gene Interaction Network
Click a node to explore
FAF2AMFRCANXP4HBUBE2G2EDEM1OS9
PROTEIN STRUCTURE
Preparing viewer…
PDB2DAM · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.28Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.16 [0.09–0.28]
RankingsWhere FAF2 stands among ~20K protein-coding genes
  • #1,975of 20,598
    Most Researched211 · top 10%
  • #957of 17,882
    Most Constrained (LOEUF)0.28 · top 10%
Genes detectedFAF2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner.
PMID: 34739333
Science · 2021
1.00
2
AAA+ ATPase chaperone p97/VCP
PMID: 39472561
Nat Commun · 2024
0.90
3
Long non-coding RNA SNHG6 couples cholesterol sensing with mTORC1 activation in hepatocellular carcinoma.
PMID: 35995997
Nat Metab · 2022
0.80
4
FAF2 is a bifunctional regulator of peroxisomal homeostasis and saturated lipid responses.
PMID: 39763943
bioRxiv · 2024
0.70
5
Genome-wide Association Study and Meta-analysis on Alcohol-Associated Liver Cirrhosis Identifies Genetic Risk Factors.
PMID: 32853455
Hepatology · 2021
0.64