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  2. Childhood onset hereditary spastic paraplegia
  3. BHLHE22

Childhood onset hereditary spastic paraplegia

Gene: BHLHE22

Amber List (moderate evidence)
BHLHE22 (basic helix-loop-helix family member e22)
EnsemblGeneIds (GRCh38): ENSG00000180828
EnsemblGeneIds (GRCh37): ENSG00000180828
OMIM: 613483, Gene2Phenotype
BHLHE22 is in 3 panels

1 review

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence to support classification of this gene as Green (tone abnormalities were present in all individuals, presenting as lower limb or appendicular spasticity in 6 patients). However, PMID:39502664 is currently still in pre-print and therefore this gene-disease association should be considered provisional pending peer-reviewed publication.
Created: 22 Sep 2025, 1:27 p.m. | Last Modified: 31 Dec 2025, 10:12 a.m.
Panel Version: 8.22
PMID: 39502664 - 11 individuals from 9 unrelated families with BHLHE22 variants, presenting with a neurodevelopmental disorder including absent or limited speech, impaired motor function, intellectual disability, involuntary movements, autistic traits, abnormal muscle tone. Most had partial or complete agenesis of the corpus callosum, and some also showed epilepsy, dysmorphic features, and eye anomalies.

Four individuals had de novo missense variants within the helix-loop-helix domain, and seven carried a recurrent homozygous frameshift variant, p.(Gly74Alafs*18).

Mice lacking bhlhe22 show nearly complete loss of three brain comminsure, including the corpus callosum, recapitulating the structural anomalies seen in affected humans.
Sources: Literature
Created: 22 Sep 2025, 10:30 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder, MONDO:0700092

Publications

Created: 22 Sep 2025, 10:30 a.m.
Last Modified: 31 Dec 2025, 10:12 a.m.
Panel version: 8.11

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Neurodevelopmental disorder, MONDO:0700092
Tags
watchlist gene-checked
OMIM
613483
Clinvar variants
Variants in BHLHE22
Penetrance
None
Publications
Panels with this gene

History Filter Activity

31 Dec 2025, Gel status: 2

Removed Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_promote_green was removed from gene: BHLHE22. Tag watchlist tag was added to gene: BHLHE22.

19 Dec 2025, Gel status: 2

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag gene-checked tag was added to gene: BHLHE22.

22 Sep 2025, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: bhlhe22 has been classified as Amber List (Moderate Evidence).

22 Sep 2025, Gel status: 1

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

Arina Puzriakova (Genomics England Curator)

gene: BHLHE22 was added gene: BHLHE22 was added to Childhood onset hereditary spastic paraplegia. Sources: Literature Q3_25_promote_green tags were added to gene: BHLHE22. Mode of inheritance for gene: BHLHE22 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: BHLHE22 were set to 39502664 Phenotypes for gene: BHLHE22 were set to Neurodevelopmental disorder, MONDO:0700092 Review for gene: BHLHE22 was set to GREEN