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Intellectual disability

Gene: WARS

Green List (high evidence)
WARS (tryptophanyl-tRNA synthetase)
EnsemblGeneIds (GRCh38): ENSG00000140105
EnsemblGeneIds (GRCh37): ENSG00000140105
OMIM: 191050, Gene2Phenotype
WARS is in 5 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 12 Mar 2026, 1:33 p.m. | Last Modified: 12 Mar 2026, 1:33 p.m.
Panel Version: 9.299
Created: 12 Mar 2026, 1:33 p.m.
Last Modified: 12 Mar 2026, 1:33 p.m.
Panel version: 9.299

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting to amber with a recommendation for green rating following GMS review as there are 4 families with intellectual disability.
Created: 9 Jul 2025, 9:59 p.m. | Last Modified: 9 Jul 2025, 9:59 p.m.
Panel Version: 9.34
Associated with Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities OMIM:620317 (AR). Also associated with Neuronopathy, distal hereditary motor, autosomal dominant 9, OMIM:617721 (AD).

5 families reported with biallelic variants in WARS1 and phenotype of intellectual disability and progressive severe microcephaly in 4 families. Variable other phenotypes were also present such as hearing loss, skeletal and brain abnormalities and seizures.

PMID: 34585293 - Okamoto et al 2022 - 4 year old female Japanese proband with compound het variants in WARS1 (p.Arg448Trp and p.Ala333Thr). Parents were heterozygous. Variants are rare. She presented with hypotonia, developmental delay, delayed myelination in the cerebral white matter. She had a seizure age 2. Severe intellectual disability at age 4, did not walk independently. Head circumference was -0.4 SD at birth and -3.4 SD by age 4.

PMID: 35815345 - Lin et al 2022 - 3 probands from 2 consanguineous Pakistani families. In family 1, one proband at age 20 had developmental delay, mild ID, mild microcephaly, mild sensorineural hearing loss. The second proband at age 16 had severe delayed developmental milestones/intellectual disability, hypotonia, severe microcephaly (-7.8 SD), severe hearing impairment and skeletal abnormalities of the legs. In family 2, the 5 year male had global developmental delay, complex partial epilepsy, a history of central adrenal insufficiency, cortical blindness, and multiple brain abnormalities. He has a history of seizures. A homozygous, rare, start loss variant (c.1A>G, p.Met1?) in exon 2 of WARS1 was identified in family 1 with parents as carriers. A homozygous c.1255G>A, p.(Asp419Asn) variant was identified in WARS1 in family 2, with parents as carriers. This variant is present in population databases with a MAF ~ 0.003 but not in the homozygous state. Zebrafish wars1 knockout displayed microcephaly, hearing loss, and musculoskeletal abnormalities, and the homozygous animals do not survive past Day 10

PMID: 35790048 - Bögershausen et al 2022 - 4 individuals from 2 families all with the same missense variant in WARS1 (c.397C>T, p.(R133C)). All 4 had progressive microcephaly with OFC at (-4.2, -4.3, -3.8 and −3.5) at assessment at ages 5, 13, 8 and 7 years. the proband from family 1 had mild ID, the three from family 2 had severe ID and two from family 2 had hypotonia. No seizures or hearing loss was reported. The WARS1 variant negatively impacts protein abundance and is unable to rescue the phenotype of a CRISPR/Cas9 wars1 knockout zebrafish model.

Created: 9 Jul 2025, 6:01 p.m. | Last Modified: 9 Jul 2025, 9:58 p.m.
Panel Version: 9.33

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, OMIM:620317; neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, MONDO:0957218

Publications

Created: 9 Jul 2025, 6:01 p.m.
Last Modified: 9 Jul 2025, 9:58 p.m.
Panel version: 9.33

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
  • Literature
Phenotypes
  • Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, OMIM:620317
  • neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, MONDO:0957218
OMIM
191050
Clinvar variants
Variants in WARS
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Mar 2026, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_promote_green was removed from gene: WARS.

12 Mar 2026, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to WARS. Source Expert Review Green was added to WARS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

9 Jul 2025, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

9 Jul 2025, Gel status: 1

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q3_25_promote_green tag was added to gene: WARS.

9 Jul 2025, Gel status: 1

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

Eleanor Williams (Genomics England Curator)

gene: WARS was added gene: WARS was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: WARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WARS were set to 34585293; 35790048; 35815345 Phenotypes for gene: WARS were set to Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, OMIM:620317; neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, MONDO:0957218 Review for gene: WARS was set to GREEN