Intellectual disability
Gene: FEM1B

FEM1B (fem-1 homolog B)
EnsemblGeneIds (GRCh38): ENSG00000169018
EnsemblGeneIds (GRCh37): ENSG00000169018
OMIM: 613539, Gene2Phenotype
FEM1B is in 2 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 26 Sep 2024, 2:57 p.m. | Last Modified: 26 Sep 2024, 2:57 p.m.

Panel Version: 7.41

Comment on list classification: As recently reviewed by Zornitza Stark, five unrelated individuals were reported with a syndromic neurodevelopmental disorder and identified with the same missense variant p.Arg126Gln. All five individuals presented with global developmental delay and all four patients tested for intellectual disability had ID.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.

Although only one variant was reported, there is functional evidence available for this variant. Hence, this gene can be promoted to green rating in the next GMS update.
Created: 27 Jun 2024, 9:06 a.m. | Last Modified: 27 Jun 2024, 9:10 a.m.

Panel Version: 6.49

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

Created: 27 Jun 2024, 8:11 a.m.
Last Modified: 27 Jun 2024, 9:10 a.m.
Panel version: 7.41

Arina Puzriakova (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Although phenotypic overlap is noted, it is not possible to ascertain whether the additional cases refer to different individuals. Also possible founder effect as all cases harbour the same variant. Additional cases/functional data are required to ascertain the contribution of FEM1B variants to an ID phenotype.
Created: 24 Jul 2020, 8:40 a.m. | Last Modified: 24 Jul 2020, 8:40 a.m.

Panel Version: 3.178

Gene not associated with any phenotype on OMIM or G2P.

Lecoquierre et al. (2019) (PMID: 31036916) conducted a large candidate gene discovery study and identified a de novo missense variant (p.Arg126Gln) in a patient with syndromic global developmental delay. Recurrence of the same variant was highlighted in an individual from the DDD study, and the another from GeneMatcher, who were said to share a similar phenotype. No function analysis was undertaken to validate the implication of FEM1B.
Created: 7 Jul 2020, 5:19 p.m. | Last Modified: 24 Jul 2020, 8:26 a.m.

Panel Version: 3.177

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global developmental delay

Publications

31036916

Created: 7 Jul 2020, 5:19 p.m.
Last Modified: 24 Jul 2020, 8:26 a.m.
Panel version: 3.179

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.
Created: 23 Apr 2024, 8:49 p.m. | Last Modified: 23 Apr 2024, 8:49 p.m.

Panel Version: 5.536

PMID: 31036916 - a single individual with de novo variant reported in a neurodevelopmental disorder cohort. Authors note another de novo case with the exact same variant (p.Arg126Gln) from the DDD study, and a 3rd patient from GeneMatcher with the same de novo missense again. The variant is in a highly constrained region of the protein. Cannot be certain the DDD and GeneMatcher individuals are unrelated, therefore I have treated as two reports for now.
Sources: Literature
Created: 23 Apr 2020, 4:24 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Syndromic disease MONDO:0002254, FEM1B-related

Publications

Created: 23 Apr 2020, 4:24 a.m.

Panel version: 5.536

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
NHS GMS

Phenotypes

neurodevelopmental disorder, MONDO:0700092
intellectual disability, MONDO:0001071

Tags

gene-checked

OMIM

613539

Clinvar variants

Variants in FEM1B

Penetrance

None

Publications

Panels with this gene

History Filter Activity

2 Oct 2024, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag gene-checked tag was added to gene: FEM1B.

26 Sep 2024, Gel status: 3