AIMP2

aminoacyl tRNA synthetase complex interacting multifunctional protein 2, the group of Small nucleolar RNA protein coding host genes|Aminoacyl tRNA synthetase complex interacting multifunctional proteins

Basic information

Region (hg38): 7:6009255-6023834

Links

ENSG00000106305 ∙ NCBI:7965 ∙ OMIM:600859 ∙ HGNC:20609 ∙ Uniprot:Q13155 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukodystrophy, hypomyelinating, 17 (Definitive), mode of inheritance: AR
• leukodystrophy, hypomyelinating, 17 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating, 17	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	29215095

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AIMP2 gene.

• Inborn genetic diseases (2 variants)
• not provided (1 variants)
• Leukodystrophy, hypomyelinating, 17 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AIMP2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				30	4	34
missense		1	61	2	4	68
nonsense	1	1	1			3
start loss						0
frameshift	1	2	1			4
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region			3		1	4
non coding				5	6	11
Total	3	4	63	37	14

Highest pathogenic variant AF is 0.0000460

Variants in AIMP2

This is a list of pathogenic ClinVar variants found in the AIMP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-6009342-C-A		Lynch syndrome	Benign (Sep 05, 2013)
7-6009379-G-C			Conflicting classifications of pathogenicity (Dec 11, 2023)
7-6009394-G-C		not specified	Benign (May 04, 2022)
7-6009406-C-G			Uncertain significance (Aug 24, 2022)
7-6009409-C-T			Uncertain significance (Aug 05, 2022)
7-6009413-G-A			Uncertain significance (Jan 18, 2022)
7-6009420-G-A		AIMP2-related disorder	Benign (Nov 27, 2023)
7-6009424-C-T			Uncertain significance (Aug 16, 2022)
7-6009426-C-T		AIMP2-related disorder	Likely benign (Jul 29, 2023)
7-6009432-C-T			Likely benign (Mar 21, 2023)
7-6009433-ATG-A		Inborn genetic diseases • Leukodystrophy, hypomyelinating, 17	Pathogenic/Likely pathogenic (Oct 03, 2022)
7-6009437-A-G		Leukodystrophy, hypomyelinating, 17	Likely pathogenic (-)
7-6009438-C-A		Inborn genetic diseases	Pathogenic (Dec 13, 2017)
7-6009444-C-T			Likely benign (Dec 03, 2021)
7-6009446-C-G			Uncertain significance (Sep 27, 2022)
7-6009450-C-G		Inborn genetic diseases	Uncertain significance (Feb 20, 2022)
7-6009456-C-A			Uncertain significance (Jul 06, 2022)
7-6009456-C-T			Likely benign (Jun 04, 2022)
7-6009457-G-T			Likely benign (Jul 01, 2022)
7-6009461-G-A			Uncertain significance (Aug 18, 2022)
7-6009464-G-A		Inborn genetic diseases	Uncertain significance (Apr 20, 2021)
7-6009464-G-C		Inborn genetic diseases	Likely benign (Oct 05, 2023)
7-6009468-C-A		Neurodevelopmental abnormality • Leukodystrophy, hypomyelinating, 17	Likely pathogenic (-)
7-6009472-C-G			Benign (Nov 27, 2023)
7-6009477-G-T			Likely benign (Jun 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AIMP2	protein_coding	protein_coding	ENST00000223029	4	14590

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00802	0.936	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.849	227	194	1.17	0.0000114	2095
Missense in Polyphen		85	75.945	1.1192		860
Synonymous	-1.57	105	86.4	1.21	0.00000584	649
Loss of Function	1.65	5	10.9	0.460	4.62e-7	128

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000612	0.000612
Ashkenazi Jewish	0.00	0.00
East Asian	0.000115	0.000109
Finnish	0.000281	0.000277
European (Non-Finnish)	0.0000889	0.0000791
Middle Eastern	0.000115	0.000109
South Asian	0.000131	0.000131
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for assembly and stability of the aminoacyl- tRNA synthase complex (PubMed:19131329). Mediates ubiquitination and degradation of FUBP1, a transcriptional activator of MYC, leading to MYC down-regulation which is required for aveolar type II cell differentiation. Blocks MDM2-mediated ubiquitination and degradation of p53/TP53. Functions as a proapoptotic factor. {ECO:0000269|PubMed:16135753, ECO:0000269|PubMed:19131329}.
• Pathway: Osteoclast Signaling;Transcriptional activation by NRF2;tRNA Aminoacylation;Translation;Metabolism of proteins;Metabolism of amino acids and derivatives;Metabolism;Selenoamino acid metabolism;SeMet incorporation into proteins;Cytosolic tRNA aminoacylation (Consensus)

Intolerance Scores

• loftool: 0.656
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.31

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.626
• ghis: 0.544

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.578

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Aimp2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: tRNA aminoacylation for protein translation;apoptotic process;negative regulation of cell population proliferation;positive regulation of protein ubiquitination;type II pneumocyte differentiation;protein-containing complex assembly;positive regulation of neuron death;positive regulation of aminoacyl-tRNA ligase activity
• Cellular component: nucleus;cytosol;membrane;aminoacyl-tRNA synthetase multienzyme complex
• Molecular function: protein binding;protein-containing complex scaffold activity