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Mendeliome

Gene: POLR1A

Green List (high evidence)

POLR1A (RNA polymerase I subunit A)
EnsemblGeneIds (GRCh38): ENSG00000068654
EnsemblGeneIds (GRCh37): ENSG00000068654
OMIM: 616404, Gene2Phenotype
POLR1A is in 11 panels

3 reviews

Lucy Spencer (Victorian Clinical Genetics Services)

I don't know

PMID: 28051070- 2 brothers in a single consanguineous family with neurological disease including leukodystrophy with a homozygous variant. Reduced protein expression in patient cells.

PMID: 36917474- A different homozygous missense to the previous family and this time seen in 2 unrelated patients. Both have developmental delay, hypomyelinating leukodystrophy and cerebellar atrophy. Experiments in fibroblast from 2 of the patients showed aberrant RNA processing and degradation. Proteomics showed abnormal protein homeostasis and ER stress responses.
The variant T642N has 15 hets all in the European non-finnish sub pop, both patients in this study are from Europe.
Created: 6 Apr 2023, 2:45 a.m. | Last Modified: 6 Apr 2023, 2:45 a.m.
Panel Version: 1.775

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy MONDO:0019046, POLR1A-related

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Evidence for association of bi-allelic variants with leukodystrophy is moderate.
Created: 6 Apr 2023, 6:58 a.m. | Last Modified: 6 Apr 2023, 6:58 a.m.
Panel Version: 1.785
Comment when marking as ready: Limited evidence for the association between bi-allelic variants and leukodystrophy.
Created: 26 Dec 2020, 11:39 p.m. | Last Modified: 26 Dec 2020, 11:39 p.m.
Panel Version: 0.5804

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 27, MIM# 620675; Acrofacial dysostosis, Cincinnati type, (MIM#616462)

Ain Roesley (Victorian Clinical Genetics Services)

Green List (high evidence)

PMID: 25913037;
- 3 patients
- 2 missense (1x de novo and the other unknown) and 1 NMD-predicted (inherited from mildly affected father)
- severity of phenotypes vary
- zebrafish models of homozygous loss of POLR1A recapitulates the craniofacial phenotype

PMID: 28051070;
- consanguineous family
- 2 affected siblings (homozygous missense)
- staining of fibroblasts showed markedly reduced protein levels
Created: 26 Dec 2020, 10:53 p.m. | Last Modified: 26 Dec 2020, 10:53 p.m.
Panel Version: 0.5800

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Acrofacial dysostosis, Cincinnati type, (MIM#616462)

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Leukodystrophy, hypomyelinating, 27, MIM# 620675
  • Acrofacial dysostosis, Cincinnati type, (MIM#616462)
OMIM
616404
Clinvar variants
Variants in POLR1A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

21 Jan 2024, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type, (MIM#616462); Leukodystrophy MONDO:0019046, POLR1A-related to Leukodystrophy, hypomyelinating, 27, MIM# 620675; Acrofacial dysostosis, Cincinnati type, (MIM#616462)

6 Apr 2023, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type, (MIM#616462); Leukodystrophy to Acrofacial dysostosis, Cincinnati type, (MIM#616462); Leukodystrophy MONDO:0019046, POLR1A-related

6 Apr 2023, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: POLR1A were set to 25913037; 28051070

6 Apr 2023, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: POLR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

26 Dec 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: polr1a has been classified as Green List (High Evidence).

26 Dec 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type, (MIM#616462) to Acrofacial dysostosis, Cincinnati type, (MIM#616462); Leukodystrophy

26 Dec 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: POLR1A were changed from to Acrofacial dysostosis, Cincinnati type, (MIM#616462)

26 Dec 2020, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: POLR1A were set to

26 Dec 2020, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: POLR1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: POLR1A was added gene: POLR1A was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: POLR1A was set to Unknown