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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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AAR2
AAR2 splicing factor
Chromosome 20 · 20q11.23
NCBI Gene: 25980Ensembl: ENSG00000131043.14HGNC: HGNC:15886UniProt: Q9Y312
83PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingspliceosomal tri-snRNP complex assemblyU5 snRNPspliceosomal snRNP assemblylipomaGlobal developmental delayMaculeHypoplasia of the corpus callosum
✦AI Summary

AAR2 is a U5 snRNP assembly factor essential for spliceosome biogenesis and pre-mRNA splicing. AAR2 functions as a placeholder protein that binds the RNase H-like domain of PRPF8, a core U5 snRNP component 1. This interaction sterically excludes the Brr2p helicase and blocks U4/U6 di-snRNA binding to PRPF8, preventing premature spliceosome activation 2. AAR2 is incorporated into nascent U5 snRNP in the cytoplasm but is subsequently displaced by Brr2 after nuclear import to form mature U5 snRNP 3. The AAR2-PRPF8 interaction is phosphorylation-dependent, with CK2α1 and SGK2 kinases capable of abrogating this interaction 4. While AAR2 is essential for in vivo splicing of U3 precursors in yeast, it is dispensable for in vitro splicing, suggesting its primary role in snRNP recycling 5. Beyond its splicing function, plant AAR2 also promotes miRNA biogenesis by stabilizing the HYL1 microprocessor component 6. Notably, AAR2 was identified as a novel susceptibility gene for Hodgkin lymphoma through transcriptome-wide association analysis 7, suggesting potential disease relevance. AAR2 functions within a regulatory network involving R2TP-HSP90 chaperones during PRPF8 biogenesis 8.

Sources cited
1
AAR2 binds PRPF8 RNase H-like domain and locks it in a conformation compatible with the first transesterification step of splicing
PMID: 36322420
2
AAR2 is a true ortholog of yeast Aar2p that binds PRPF8 RH domain and is part of the human proteome
PMID: 26527271
3
AAR2 is incorporated into nascent U5 snRNP in the cytoplasm and is mutually exclusive with Brr2, which replaces it after nuclear import
PMID: 23727230
4
CK2α1 and SGK2 kinases can abrogate the AAR2-PRPF8 interaction, demonstrating phosphorylation-dependent regulation
PMID: 35225431
5
AAR2 is essential for in vivo splicing and U5 snRNP recycling but not required for splicing in vitro
PMID: 11720285
6
Plant AAR2 interacts with HYL1 and promotes miRNA biogenesis through stabilization of the active form of HYL1
PMID: 36191209
7
AAR2 was identified as a novel susceptibility gene for Hodgkin lymphoma through transcriptome-wide association analysis
PMID: 40392315
8
AAR2 participates in U5 snRNP assembly as part of a network involving R2TP-HSP90 chaperones and other PRPF8 biogenesis factors
PMID: 34951455
Disease Associationsⓘ20
lipomaOpen Targets
0.32Weak
Anteriorly placed anusOpen Targets
0.26Weak
cerebellar malformationOpen Targets
0.26Weak
Global developmental delayOpen Targets
0.26Weak
Hypoplasia of the corpus callosumOpen Targets
0.26Weak
MaculeOpen Targets
0.26Weak
microcephalyOpen Targets
0.26Weak
Patent foramen ovaleOpen Targets
0.26Weak
ventricular septal defectOpen Targets
0.26Weak
sleep apneaOpen Targets
0.19Weak
supraventricular ectopyOpen Targets
0.17Weak
placental retentionOpen Targets
0.09Suggestive
Abnormality of the skeletal systemOpen Targets
0.03Suggestive
hair colorOpen Targets
0.02Suggestive
liver cancerOpen Targets
0.01Suggestive
colorectal adenocarcinomaOpen Targets
0.00Suggestive
colorectal carcinomaOpen Targets
0.00Suggestive
brain cancerOpen Targets
0.00Suggestive
glioblastomaOpen Targets
0.00Suggestive
neoplasmOpen Targets
0.00Suggestive
Pathogenic Variants1
NM_001271874.2(AAR2):c.520G>A (p.Val174Met)Likely pathogenic
8 conditions
☆☆☆☆2016→ Residue 174
View on ClinVar ↗
Related Genes
SNRPD1Protein interaction100%SNRPD2Protein interaction100%SNRPNProtein interaction100%SNRPFProtein interaction100%SNRPBProtein interaction100%SNRPEProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
91%
Lung
90%
Liver
90%
Ovary
88%
Brain
82%
Gene Interaction Network
Click a node to explore
AAR2SNRPD1SNRPD2SNRPNSNRPFSNRPBSNRPE
PROTEIN STRUCTURE
Preparing viewer…
PDB7PJH · 2.35 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.47LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.09 [0.82–1.47]
RankingsWhere AAR2 stands among ~20K protein-coding genes
  • #5,709of 20,598
    Most Researched83
  • #4,947of 5,498
    Most Pathogenic Variants1
  • #15,001of 17,882
    Most Constrained (LOEUF)1.47
Genes detectedAAR2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Structural and functional investigation of the human snRNP assembly factor AAR2 in complex with the RNase H-like domain of PRPF8.
PMID: 36322420
Acta Crystallogr D Struct Biol · 2022
1.00
2
Crystallization and biochemical characterization of the human spliceosomal Aar2-Prp8(RNaseH) complex.
PMID: 26527271
Acta Crystallogr F Struct Biol Commun · 2015
0.90
3
PMID: 36191209
Proc Natl Acad Sci U S A · 2022
0.80
4
CryoEM of RUVBL1-RUVBL2-ZNHIT2, a complex that interacts with pre-mRNA-processing-splicing factor 8.
PMID: 34951455
Nucleic Acids Res · 2022
0.70
5
Integration of transcriptome-wide association study and gene-based association analysis identifies candidate genes for Hodgkin lymphoma.
PMID: 40392315
J Cancer Res Clin Oncol · 2025
0.60