Severe microcephaly
Gene: TYW1EnsemblGeneIds (GRCh38): ENSG00000198874
EnsemblGeneIds (GRCh37): ENSG00000198874
OMIM: 611243, Gene2Phenotype
TYW1 is in 3 panels
1 review
Ida Ertmanska (Genomics England Curator)
Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Mouse and zebrafish knockout models showed microcephaly, supportive of the disease association. Based on available evidence, this gene can only be rated Amber on this panel.Created: 27 Mar 2026, 2:30 p.m. | Last Modified: 27 Mar 2026, 2:32 p.m.
Panel Version: 8.39
PMID: 34077496 Li et al., 2021
2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q.
Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID); head circumference at 6yrs: 47.5 cm (−3.26 SD).
CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID). Head circumference was 49 cm at 14yrs (−3.64 SD).
Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes.
Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests. Microcephaly and neurological manifestation were observed in both mice and zebrafish.
PMID: 38706838 Sun et al., 2024
Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted.
TYW1 is not yet associated with a phenotype in OMIM, ClinGen or G2P (accessed 17 Mar 2026).
Sources: LiteratureCreated: 27 Mar 2026, 2:29 p.m. | Last Modified: 27 Mar 2026, 2:31 p.m.
Panel Version: 8.38
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
cerebral palsy, MONDO:0006497; microcephaly, MONDO:0001149
Publications
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Amber
- Literature
- Phenotypes
-
- cerebral palsy, MONDO:0006497
- microcephaly, MONDO:0001149
- OMIM
- 611243
- Clinvar variants
- Variants in TYW1
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Gene: tyw1 has been classified as Amber List (Moderate Evidence).
Removed Tag
Ida Ertmanska (Genomics England Curator)Tag watchlist was removed from gene: TYW1.
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Gene: tyw1 has been classified as Red List (Low Evidence).
Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes
Ida Ertmanska (Genomics England Curator)gene: TYW1 was added gene: TYW1 was added to Severe microcephaly. Sources: Literature watchlist tags were added to gene: TYW1. Mode of inheritance for gene: TYW1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TYW1 were set to 34077496 Phenotypes for gene: TYW1 were set to cerebral palsy, MONDO:0006497; microcephaly, MONDO:0001149 Review for gene: TYW1 was set to AMBER