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  3. BHLHE22
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Fetal anomalies

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

5 reviews

Ida Ertmanska (Genomics England Curator)

This gene and phenotype were reviewed during meetings in July and August 2026. The meetings included representatives of the North Thames and Central and South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler & Louise Carr (North Thames GLH), Sarah Graham & Elizabeth Young (Central & South GLH), and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Sunayna Best, Soo-Mi Park & Tessa Homfray (R21 Clinical Oversight Group).
Created: 29 Oct 2026, 4:13 p.m. | Last Modified: 29 Oct 2026, 4:13 p.m.
Panel Version: 8.26
Created: 29 Oct 2026, 4:13 p.m.
Last Modified: 29 Oct 2026, 4:13 p.m.
Panel version: 8.26

Louise Carr (North Thames Genomic Medicine Service)

Green List (high evidence)

I have found this in gnomad but the SNV is 13-41318874-C-T but I think the variant is 13- 41893010-C-T as 41893010 is the position of the variant. Paper published so can be moved from amber to green. The gene had been discussed in previous reviews and the paper that was in preprint has now been published.
Created: 29 Oct 2026, 3:51 p.m. | Last Modified: 29 Oct 2026, 3:51 p.m.
Panel Version: 8.25

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

Created: 29 Oct 2026, 3:51 p.m.
Last Modified: 29 Oct 2026, 3:51 p.m.
Panel version: 8.25

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 12 Dec 2025, 3:10 p.m. | Last Modified: 12 Dec 2025, 3:10 p.m.
Panel Version: 6.120
Created: 12 Dec 2025, 3:10 p.m.
Last Modified: 12 Dec 2025, 3:10 p.m.
Panel version: 6.120

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

PMID:39502664 is currently still in pre-print and therefore this gene-disease association should be considered provisional pending peer-reviewed publication. Discussed with R21 expert group and agreed to demote to Amber awaiting publication.
Created: 31 Dec 2025, 10:15 a.m. | Last Modified: 2 Jan 2026, 4:43 p.m.
Panel Version: 6.133
New gene added to this panel. There is sufficient evidence to make this gene Green at the next GMS panel update, inline with the recent review by the R21 Clinical Oversight Group.
Created: 5 Sep 2025, 4:41 p.m. | Last Modified: 5 Sep 2025, 4:41 p.m.
Panel Version: 6.29
Created: 5 Sep 2025, 4:41 p.m.
Last Modified: 2 Jan 2026, 4:43 p.m.
Panel version: 6.129

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

Green List (high evidence)

This gene and phenotype were reviewed during meetings in June & July 2025. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler & Elizabeth Scotchman (North Thames GLH), Natalie Bibb, Stephanie Allen & Sarah Graham (Central & South GLH) and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Elizabeth Wall, Sunayna Best, Soo-Mi Park & Sahar Mansour (R21 Clinical Oversight Group).
Created: 5 Sep 2025, 4:31 p.m. | Last Modified: 5 Sep 2025, 4:31 p.m.
Panel Version: 6.28
Variants in 11 individuals from 9 unrelated families with a neurodevelopmental disorder. The majority of individuals have partial or complete agenesis of the corpus callosum. Mice lacking bhlhe22 show nearly complete loss of three brain commissures, including the corpus callosum. Four individuals have de novo missense variants within the helix-loop-helix domain and 7 individuals from 5 families have a recurrent homozygous frameshift variant, p.(Gly74Alafs*18).
Created: 5 Sep 2025, 2:55 p.m. | Last Modified: 5 Sep 2025, 2:55 p.m.
Panel Version: 6.24

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Complex neurodevelopmental disorder

Publications

Created: 5 Sep 2025, 2:55 p.m.
Last Modified: 5 Sep 2025, 2:55 p.m.
Panel version: 6.28

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • neurodevelopmental disorder, MONDO:0700092
  • Complex neurodevelopmental disorder
Tags
gene-checked Q3_26_promote_green
OMIM
613483
Clinvar variants
Variants in BHLHE22
Penetrance
None
Publications
Panels with this gene

History Filter Activity

2 Nov 2026, Gel status: 2

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q3_26_promote_green tag was added to gene: BHLHE22.

29 Oct 2026, Gel status: 2

Set Phenotypes, Set publications

Ida Ertmanska (Genomics England Curator)

Added phenotypes neurodevelopmental disorder, MONDO:0700092 for gene: BHLHE22 Publications for gene: BHLHE22 were updated from 39502664 to 39502664; 42586785

16 Oct 2026, Gel status: 2

Removed Tag

Ida Ertmanska (Genomics England Curator)

Tag watchlist was removed from gene: BHLHE22.

2 Jan 2026, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

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

2 Jan 2026, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to gene: BHLHE22.

19 Dec 2025, Gel status: 3

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

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

12 Dec 2025, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_25_promote_green was removed from gene: BHLHE22. Tag Q3_25_NHS_review was removed from gene: BHLHE22.

12 Dec 2025, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Green was added to BHLHE22. Source NHS GMS was added to BHLHE22. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

8 Sep 2025, Gel status: 2

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_promote_green tag was added to gene: BHLHE22. Tag Q3_25_NHS_review tag was added to gene: BHLHE22.

5 Sep 2025, Gel status: 2

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

Arina Puzriakova (Genomics England Curator)

gene: BHLHE22 was added gene: BHLHE22 was added to Fetal anomalies. Sources: Expert Review Amber 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 Complex neurodevelopmental disorder