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Intellectual disability

Gene: POLR3B

Green List (high evidence)

POLR3B (RNA polymerase III subunit B)
EnsemblGeneIds (GRCh38): ENSG00000013503
EnsemblGeneIds (GRCh37): ENSG00000013503
OMIM: 614366, Gene2Phenotype
POLR3B is in 9 panels

4 reviews

Arina Puzriakova (Genomics England Curator)

Comment on mode of inheritance: Both biallelic and monoallelic variants have been linked to ID. There is enough evidence for a Green rating for both allelic requirements, so POLR3B has been tagged Q2_21_MOI to change the MOI from biallelic to both biallelic/monoallelic at the next GMS review.
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Biallelic variants in POLR3B are a well-established cause of hypomyelinating leukodystrophy (OMIM:614381), associated with variable ID.

Recently, heterozygous variants were also linked to ID. Djordjevic et al. 2021 (PMID:33417887) identified different de novo POLR3B variants in 6 unrelated individuals. The majority had some degree of DD, with 5/6 participants being diagnosed with intellectual disability ranging from mild to moderate severity. Four individuals required assistance with basic activities of daily living, however none had developmental regression. Protein modelling and proteomic analysis shows variants caused aberrant association of individual enzyme subunits rather than affecting overall enzyme assembly or stability.
Created: 16 Jun 2021, 1:23 p.m. | Last Modified: 16 Jun 2021, 1:23 p.m.
Panel Version: 3.1133

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
LEUKODYSTROPHY, HYPOMYELINATING, 8, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM

Publications

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known . Main mutation mechanism : All missense/in frame; Loss of function
Created: 27 Jul 2017, 8:06 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; find_uk10k; gilissen_2014_known; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; All missense/in frame; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 1:09 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Mode of pathogenicity

Lu Raymond (university of cambridge )

Green List (high evidence)

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381
  • POLR3B-related neurodevelopmental disorder
  • Ataxia, spasticity, and demyelinating neuropathy
Tags
Q2_21_MOI
OMIM
614366
Clinvar variants
Variants in POLR3B
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

16 Jun 2021, Gel status: 3

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: POLR3B were set to

16 Jun 2021, Gel status: 3

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: POLR3B was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

16 Jun 2021, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_MOI tag was added to gene: POLR3B.

16 Jun 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: POLR3B were changed from Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381 to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381; POLR3B-related neurodevelopmental disorder; Ataxia, spasticity, and demyelinating neuropathy

16 Jun 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: POLR3B were changed from Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropichypogonadism, 614381; LEUKODYSTROPHY, HYPOMYELINATING, 8, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 1

Set Mode of Inheritance, Added New Source

Ellen McDonagh (Genomics England Curator)

POLR3B was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene POLR3B was set to BIALLELIC, autosomal or pseudoautosomal

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

POLR3B was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen