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Intellectual disability

Gene: UFC1

Amber List (moderate evidence)

UFC1 (ubiquitin-fold modifier conjugating enzyme 1)
EnsemblGeneIds (GRCh38): ENSG00000143222
EnsemblGeneIds (GRCh37): ENSG00000143222
OMIM: 610554, Gene2Phenotype
UFC1 is in 5 panels

3 reviews

Catherine Snow (Genomics England)

Comment on list classification: UFC1 identified in literature PMID:30914295 as missing in PanelApp compared to other curated gene list for ID genes. Concur with Rebecca's Amber rating, that there are currently only two distinct variants/cases UFC1.
Created: 23 May 2019, 3:03 p.m.

Rebecca Foulger (Genomics England curator)

Maddirevula et al 2019 (PMID:30237576) searched their database on exomes in search of homozygous variants that could be linked to diseases. They identified the NM_016406.3:c.317C>T:p.(Thr106Ile) variant in UFC1 in two cases with global DD and progressive microcephaly (17-3196 and 17-3892). Both of these cases were published in Nahorski et al, 2018 (PMID:29868776, Table 1).
Created: 16 May 2019, 11:04 a.m.
Added 'watchlist' tag.
Created: 14 May 2019, 4 p.m.
Comment on list classification: UFC1 was added to the ID panel and rated Green by Konstantinos Varvagiannis. Changed rating from Grey to Amber based on literature evidence: PMID:29868776 (Nahorski et al. 2018) identified a homozygous missense variant in the UFC1 gene (T106I) in 7 affected members of 3 consanguineous Saudi families. All members displayed Global Developmental delay. Two of the sisters were previously reported by Anazi et al. (2017, PMID:27431290). Although the Saudi families were said to be unrelated, the families shared a haplotype, suggesting a founder effect. An unrelated Swiss boy was found to have a different homozygous variant in the UFC1 gene (R23Q). There are therefore currently two distinct variants/cases. Based on the Founder effect of the three Saudi families, I have rated as Amber awaiting a further unrelated case.
Created: 14 May 2019, 3:58 p.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Biallelic UFC1 mutations cause Neurodevelopmental disorder with spasticity and poor growth, MIM 618076.

PMID: 29868776 describes 7 individuals (most) born to consanguineous Saudi families (in one case the parents were not consanguineous but originated from the same tribe) as well as a further individual born to distantly related Swiss parents. One of these patients was previously briefly published by the same authors (PMID: 27431290).

The phenotype consisted of developmental delay (8/8 - usually profound), failure to thrive (8/8), short stature and microcephaly (both observed in 7/8), seizures (4/8) and variable brain MRI anomalies in some of these subjects.

Overall, two UFC1 missense variants are reported [NM_016406.3:c.317C>T or p.(Thr106Ile) and c.68G>A or p.(Arg23Gln) the former in the Saudi individuals]. Functional studies demonstrated the hypomorphic nature of the variants.

UFC1 (as well as UFM1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

As a result this gene can be considered for inclusion in the ID panel as green (or amber).
Sources: Literature, Expert Review
Created: 20 Nov 2018, 10:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with spasticity and poor growth, 618076

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
  • Expert Review Amber
Phenotypes
  • global developmental delay with progressive microcephaly
  • Neurodevelopmental disorder with spasticity and poor growth, 618076
Tags
watchlist
OMIM
610554
Clinvar variants
Variants in UFC1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

25 Jul 2019, Gel status: 2

Set Phenotypes, Set publications

Catherine Snow (Genomics England)

Added phenotypes Neurodevelopmental disorder with spasticity and poor growth, 618076 for gene: UFC1 Publications for gene UFC1 were changed from 29868776; 27431290; 30237576 to 30914295

16 May 2019, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: UFC1 were changed from Neurodevelopmental disorder with spasticity and poor growth, 618076 to Neurodevelopmental disorder with spasticity and poor growth, 618076; global developmental delay with progressive microcephaly

16 May 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: UFC1 were set to 29868776; 27431290

14 May 2019, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: UFC1.

14 May 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: ufc1 has been classified as Amber List (Moderate Evidence).

14 May 2019, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: UFC1 were set to 29868776

20 Nov 2018, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: UFC1 was added gene: UFC1 was added to Intellectual disability. Sources: Literature,Expert Review Mode of inheritance for gene: UFC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UFC1 were set to 29868776 Phenotypes for gene: UFC1 were set to Neurodevelopmental disorder with spasticity and poor growth, 618076 Penetrance for gene: UFC1 were set to Complete Review for gene: UFC1 was set to GREEN