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Intellectual disability

Gene: AIMP2

Amber List (moderate evidence)
AIMP2 (aminoacyl tRNA synthetase complex interacting multifunctional protein 2)
EnsemblGeneIds (GRCh38): ENSG00000106305
EnsemblGeneIds (GRCh37): ENSG00000106305
OMIM: 600859, Gene2Phenotype
AIMP2 is in 3 panels

3 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are 6 unrelated individuals reported in literature with biallelic AIMP2 variants and a complex neurodevelopmental phenotype. 5/6 presentations included syndromic ID/DD. Based on the available evidence, this gene should be promoted to Green for Intellectual disability.
Created: 19 Jan 2026, 2:08 p.m. | Last Modified: 19 Jan 2026, 2:08 p.m.
Panel Version: 9.236
Additional cases:
PMID: 38374194 Abolhassani et al., 2024
Patient 925, 3yo Iranian female, with NM_006303.4(AIMP2):c.34_35delinsC (p.Gly12ProfsTer?). She presented with: Preterm birth; Low birth weight; Microcephaly; Mild learning difficulty; Developmental delay, speech & motor; Epilepsy; Hypertonia; Limb atrophy & spasticity; Muscle weakness; Strabismus; Ophthalmoplegia; Visual impairment; Anemia. Also homozygous for a VUS SBF1 variant p.Met524Arg (SBF1 is associated with recessive CMT).

PMID: 35140751 Mazaheri et al., 2022
Iranian proband - 7-month-old infant with a progressive neurological disorder characterized by lack of development, weight loss, severe anemia, skeletal abnormalities, microcephaly and MR imaging features of leukodystrophy. WES revealed a homozygous AIMP2 c.670A>T (p.Lys224Ter) variant, confirmed het in each parent. No mention of seizures. Variant predicted to escape NMD.

PMID: 35568357 Masih et al., 2022
Patient F32.1 - 5yo Indian male - homozygous for NM_006303.4(AIMP2):c.74A>G (p.Tyr25Cys). Clinical presentation: severe DD/ID, generalised tonic-clonic seizures, dysmorphic features, short stature, feeding difficulties, spastic quadriparesis, thin corpus callosum on MRI. Diagnosed with Leukodystrophy, hypomyelinating, 17.

PMID: 26795593 Helbig et al., 2016
Proband with Epileptic encephalopathy. Compound het for AIMP2 c.575-2A>G and c.72_73del (p.Met24IlefsTer25). Patient also has alteration in LRFN2 (not associated with disease in OMIM).

This gene is associated with AR Leukodystrophy, hypomyelinating, 17, MIM:618006 (OMIM accessed 19th Jan 2025). The association between AIMP2 and AR leukodystrophy, hypomyelinating, 17 has been classified as Definitive in ClinGen (Leukodystrophy and Leukoencephalopathy Expert Panel, Sept 2025).
Created: 19 Jan 2026, 2:02 p.m. | Last Modified: 19 Jan 2026, 2:06 p.m.
Panel Version: 9.236

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 17, OMIM:618006

Publications

Created: 19 Jan 2026, 2:02 p.m.
Last Modified: 19 Jan 2026, 2:06 p.m.
Panel version: 9.236

Louise Daugherty (Genomics England Curator)

Comment on list classification: New gene added by external expert and reviewed by curation team, enough evidence to support gene-disease association and relevance to this panel to rate this gene currently as Amber
Created: 20 Feb 2019, 5:37 p.m.
Created: 20 Feb 2019, 5:37 p.m.

Panel version: 2.699

Konstantinos Varvagiannis (Other)

I don't know

Biallelic pathogenic variants in AIMP2 cause Leukodystrophy, hypomyelinating, 17 (MIM 618006).

3 individuals from 2 unrelated consanguineous families, of Indian origin have been reported (all in PMID: 29215095).

The phenotype consisted of feeding difficulties, lack of development with intellectual disability and seizures as well as brain MRI abnormalities (cerebral and cerebellar atrophy, hypo-intensities of the basal ganglia on T2w sequences). Severe microcephaly was observed in 2 patients for whom this information was available (birth measurements not specified).

All patients described to date were homozygous for a nonsense variant [NM_006303.3:c.105C>A or p.(Tyr35Ter)] which appears to be a founder mutation in this population.

Quantitative reverse transcription PCR demonstrated reduced mRNA levels in peripheral lymphocytes, but this decrease was not significant compared to controls (the authors presume low level of NMD).

Previous mouse models provide some - but not substantial - support.

The authors note marked similarity with the phenotype associated with AIMP1 (Leukodystrophy, hypomyelinating, 3 - MIM 260600), another auxiliary protein of the macromolecular multienzyme multi-tRNA synthetase complex. AIMP1 is listed in the current panel as green.

AIMP2 is not associated with any phenotype in G2P.

This gene is included in gene panels for ID offered by some diagnostic laboratories (incl. Radboudumc).

As a result, AIMP2 can be considered for inclusion in this panel probably as amber.
Sources: Literature, Radboud University Medical Center, Nijmegen
Created: 14 Dec 2018, 6:17 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 17 (MIM 618006)

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 14 Dec 2018, 6:17 p.m.

Panel version: 2.584

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Leukodystrophy, hypomyelinating, 17,OMIM:618006
  • leukodystrophy, hypomyelinating, 17, MONDO:0054817
  • neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis
Tags
Q1_26_promote_green
OMIM
600859
Clinvar variants
Variants in AIMP2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

23 Jan 2026, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: AIMP2 were changed from Leukodystrophy, hypomyelinating, 17, 618006; leukodystrophy, hypomyelinating, 17, MONDO:0054817; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis to Leukodystrophy, hypomyelinating, 17,OMIM:618006; leukodystrophy, hypomyelinating, 17, MONDO:0054817; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis

23 Jan 2026, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: AIMP2 were set to 29215095

23 Jan 2026, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: AIMP2 were changed from Leukodystrophy, hypomyelinating, 17, 618006; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis to Leukodystrophy, hypomyelinating, 17, 618006; leukodystrophy, hypomyelinating, 17, MONDO:0054817; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis

19 Jan 2026, Gel status: 2

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q1_26_promote_green tag was added to gene: AIMP2.

20 Feb 2019, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: AIMP2 were changed from Leukodystrophy, hypomyelinating, 17, 618006; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis to Leukodystrophy, hypomyelinating, 17, 618006; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis

20 Feb 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: aimp2 has been classified as Amber List (Moderate Evidence).

20 Feb 2019, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: AIMP2 were changed from Leukodystrophy, hypomyelinating, 17 (MIM 618006) to Leukodystrophy, hypomyelinating, 17, 618006; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis

14 Dec 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: AIMP2 was added gene: AIMP2 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: AIMP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AIMP2 were set to 29215095 Phenotypes for gene: AIMP2 were set to Leukodystrophy, hypomyelinating, 17 (MIM 618006) Penetrance for gene: AIMP2 were set to Complete Review for gene: AIMP2 was set to AMBER gene: AIMP2 was marked as current diagnostic