Hereditary spastic paraplegia - childhood onset

Gene: POLR3K

Amber List (moderate evidence)

POLR3K (RNA polymerase III subunit K)
EnsemblGeneIds (GRCh38): ENSG00000161980
EnsemblGeneIds (GRCh37): ENSG00000161980
OMIM: 606007, Gene2Phenotype
POLR3K is in 6 panels

2 reviews

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype.

PMID: 30584594. 2 affected individuals from 2 consanguineous families from same area in Algeria. Affected indviduals had global developmental delay with loss of motor, speech and cognitive milestones. Individuals also showed signs of nystagmus, ataxia, dystonia and spasticity. Both individuals had feeding difficulties and were tube fed, growth failure and microcephaly (-3 SD), and cryptorchidism. 1 patient had optic atrophy and hypodontia and the other patient had hypogonadotropic hypogonadism. Both individuals have the same variant (may be founder effect).

As other members of the same gene family are linked to similar phenotypes this gene has been given an Amber rating.
Created: 19 May 2021, 10:07 a.m. | Last Modified: 19 May 2021, 10:07 a.m.
Panel Version: 1.98

Zornitza Stark (Australian Genomics)

I don't know

Two individuals from same ethnic background reported with a common homozygous missense variant in this gene, suggestive of founder effect. Some functional evidence, and note other gene family members are linked to similar phenotypes.

Neurodegenerative phenotype: global developmental delay apparent from infancy with loss of motor, speech, and cognitive milestones in the first decades of life.
Sources: Literature
Created: 10 May 2021, 10:23 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Hypomyelinating leukodystrophy-21, MIM#619310



Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Amber
  • Literature
  • Leukodystrophy, hypomyelinating, 21, OMIM:619310
watchlist founder-effect
Clinvar variants
Variants in POLR3K
Panels with this gene

History Filter Activity

19 May 2021, Gel status: 2

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

Ivone Leong (Genomics England Curator)

gene: POLR3K was added gene: POLR3K was added to Hereditary spastic paraplegia - childhood onset. Sources: Literature,Expert Review Amber watchlist, founder-effect tags were added to gene: POLR3K. Mode of inheritance for gene: POLR3K was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLR3K were set to 30584594; 33659930 Phenotypes for gene: POLR3K were set to Leukodystrophy, hypomyelinating, 21, OMIM:619310