Cerebellar hypoplasia

Gene: HEATR5B

Green List (high evidence)

HEATR5B (HEAT repeat containing 5B)
EnsemblGeneIds (GRCh38): ENSG00000008869
EnsemblGeneIds (GRCh37): ENSG00000008869
HEATR5B is in 5 panels

4 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Upgrading from Amber to Green on this 100K panel as there are three unrelated cases (2 published, 1 NHS-diagnosed) with pontocerebellar hypoplasia due to biallelic variants in this gene.
Created: 17 Oct 2025, 2:06 p.m. | Last Modified: 17 Oct 2025, 2:06 p.m.
Panel Version: 1.81
As per review by Karen Stals, we have received confirmation of an unpublished NHS-diagnosed family, with three affected individuals presenting with pontocerebellar hypoplasia. The variant, present in a homozygous state in the affected individuals, had a splicing impact and confirmed out-of-frame skipping of exon 30.
Created: 17 Oct 2025, 2:04 p.m. | Last Modified: 17 Oct 2025, 2:04 p.m.
Panel Version: 1.80

Karen Stals (Royal Devon and Exeter Hospital)

Green List (high evidence)

Four affected children from two families presenting with pontocerebellar hypoplasia with neonatal seizures, severe ID and motor delay reported by Ghosh et al 2021. Additional family identified through the R14 WGS service in the Exeter Genomics Laboratory with the causative variant co-segregating in multiple affected family members.
Created: 26 Apr 2023, 11:56 p.m. | Last Modified: 27 Apr 2023, 12:01 a.m.
Panel Version: 1.72

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia

Publications

Variants in this GENE are reported as part of current diagnostic practice

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Created: 14 Jul 2021, 1:40 p.m. | Last Modified: 14 Jul 2021, 1:40 p.m.
Panel Version: 3.1188

Zornitza Stark (Australian Genomics)

I don't know

Four affected children from two families presenting with pontocerebellar hypoplasiawith neonatal seizures, severe ID and motor delay. Two homozygous splice variants were reported (c.5051–1G>A and c.5050+4A>G) in intron 31 of HEATR5B gene. Aberrant splicing was found in patient fibroblasts, which correlated with reduced levels of HEATR5B protein. Homozygous knockout mice were not viable
Sources: Literature
Created: 9 Jul 2021, 5:12 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
pontocerebellar hypoplasia; intellectual disability; seizures

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • pontocerebellar hypoplasia, MONDO:0020135
  • intellectual disability, MONDO:0001071
  • seizures
Clinvar variants
Variants in HEATR5B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Oct 2025, Gel status: 3

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: heatr5b has been classified as Green List (High Evidence).

17 Oct 2025, Gel status: 2

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist was removed from gene: HEATR5B.

14 Jul 2021, Gel status: 2

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

Ivone Leong (Genomics England Curator)

gene: HEATR5B was added gene: HEATR5B was added to Cerebellar hypoplasia. Sources: Expert Review Amber,Literature watchlist tags were added to gene: HEATR5B. Mode of inheritance for gene: HEATR5B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HEATR5B were set to 33824466 Phenotypes for gene: HEATR5B were set to pontocerebellar hypoplasia, MONDO:0020135; intellectual disability, MONDO:0001071; seizures