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Intellectual disability

Gene: FICD

Amber List (moderate evidence)
FICD (FIC domain containing)
EnsemblGeneIds (GRCh38): ENSG00000198855
EnsemblGeneIds (GRCh37): ENSG00000198855
FICD is in 6 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Paper by Perera et al 2022 has now been published (PMID: 36704923).

An additional 6 unrelated families have been reported with biallelic variants in this gene presenting with motor neuron disease. Unlike the cases reported by Perera et al, these individuals did not display any significant cognitive deficits (PMID: 36136088; 40062579). Therefore maintaining the Amber rating on this panel.
Created: 13 Oct 2025, 4:26 p.m. | Last Modified: 13 Oct 2025, 4:27 p.m.
Panel Version: 9.127
Created: 13 Oct 2025, 4:26 p.m.
Last Modified: 13 Oct 2025, 4:27 p.m.
Panel version: 9.127

Eleanor Williams (Genomics England Curator)

Comment on list classification: Promoting from red to amber, but with a watchlist tag added.
3 cases reported but all with the same variant and 2 families share a common haplotype. Some functional data. In addition the paper is still at the pre-print stage and so has not yet been peer reviewed.
Created: 27 Sep 2022, 10:51 p.m. | Last Modified: 27 Sep 2022, 10:51 p.m.
Panel Version: 2.53
Gene does not appear to be in OMIM.

As expert reviewer reports the pre-print by Perera et al 2022 report 5 individuals, from 3 consanguineous families, diagnosed with infancy-onset diabetes mellitus and neurodevelopmental abnormalities (4/5 had severe developmental delay). All were found to have a homozygous variant p.(Arg371Ser) mutation in FICD. Family 1 and Family 3 where found to share a 4.5Mb haplotype that includes FICD which suggests the variant was inherited from a common distant ancestor. Functional studies showed that the variant partially compromises BiP AMPylation in vitro and eliminates all
detectable deAMPylation activity.
Created: 27 Sep 2022, 10:45 p.m. | Last Modified: 27 Sep 2022, 10:45 p.m.
Panel Version: 2.50
Review on behalf of Jayne Houghton and Kevin Colclough, Exeter Genomics Laboratory, SWGLH. Perera et al 2022 (medRxiv preprint doi: https://doi.org/10.1101/2022.05.14.22275020) reported a genetic syndrome of neonatal diabetes, severe developmental delay and skeletal abnormalities due to a homozygous variant, p.(Arg371Ser), in the FICD gene in 5 affected individuals from 3 different families. The disease mechanism likely consists of an intra-organellar perturbation that compromises both insulin-producing beta cells and cells relevant to neurological development and/or function. Functional studies of the specific variant identified in the reported families to date suggests a variant-specific mechanism, causing inappropriately elevated levels of AMPylated BiP as opposed to overall loss of gene function.
Created: 14 Sep 2022, 4:42 p.m. | Last Modified: 14 Sep 2022, 4:42 p.m.
Panel Version: 2.40

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neonatal diabetes, severe neurodevelopmental delay and skeletal abnormalities.

Created: 14 Sep 2022, 4:42 p.m.
Last Modified: 14 Sep 2022, 4:42 p.m.
Copied from panel: Diabetes - neonatal onset v2.53

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert review
Phenotypes
  • Neonatal diabetes
  • Neonatal insulin-dependent diabetes mellitus, HP:0000857
  • severe neurodevelopmental delay, HP:0012758
  • skeletal abnormalities.
Tags
watchlist
Clinvar variants
Variants in FICD
Penetrance
None
Publications
Panels with this gene

History Filter Activity

19 Mar 2026, Gel status: 2

Removed Tag

Ida Ertmanska (Genomics England Curator)

Tag gene-checked was removed from gene: FICD.

19 Mar 2026, Gel status: 2

Added Tag

Ida Ertmanska (Genomics England Curator)

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

13 Oct 2025, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: FICD were set to

27 Sep 2022, Gel status: 2

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

Eleanor Williams (Genomics England Curator)

gene: FICD was added gene: FICD was added to Intellectual disability. Sources: Expert review,Expert Review Amber watchlist tags were added to gene: FICD. Mode of inheritance for gene: FICD was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FICD were set to Neonatal diabetes; Neonatal insulin-dependent diabetes mellitus, HP:0000857; severe neurodevelopmental delay, HP:0012758; skeletal abnormalities.