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Intellectual disability

Gene: SEL1L

Amber List (moderate evidence)
SEL1L (SEL1L ERAD E3 ligase adaptor subunit)
EnsemblGeneIds (GRCh38): ENSG00000071537
EnsemblGeneIds (GRCh37): ENSG00000071537
OMIM: 602329, Gene2Phenotype
SEL1L is in 2 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: As reviewed by Julia Baptista, there is sufficient evidence available (three unrelated families) for the association of this gene with intellectual disability. Hence, this gene can be promoted to green rating in the next GMS update.
Created: 1 May 2025, 6:09 p.m. | Last Modified: 1 May 2025, 6:09 p.m.
Panel Version: 9.12
PMID:37943610 reported six patients from three unrelated families with a neurodevelopmental disorder involving developmental delay, intellectual disability, facial dysmorphisms, short stature, microcephaly and seizures. Five patients from two families (Saudi Arabian and Moroccan descent) were identified with homozygous SEL1L variants (p.(Gly585Asp) & p.(Met528Arg)), while an unrelated patient of Italian descent was identified with homozygous HRD1 variant. The variants were hypomorphic and impaired endoplasmic reticulum (ER)-associated degradation.

PMID:37943617 reported the identification of a homozygous SEL1L variant (p.(Cys141Tyr)) in five patients from a consanguineous Slovakian family. These patients presented with not only ERAD-associated neurodevelopmental disorders with onset in infancy (ENDI) syndromes, but infantile-onset agammaglobulinemia with no mature B cells, resulting in frequent infections and early death. All patients exhibited intellectual disability and were unable to speak words and sentences.

This gene has been associated with relevant phenotypes in OMIM (MIMs #621067 & #621068), but not yet in Gene2Phenotype.
Created: 1 May 2025, 5:57 p.m. | Last Modified: 1 May 2025, 6:06 p.m.
Panel Version: 9.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with hypotonia, poor growth, dysmorphic facies, and agammaglobulinemia, OMIM:621068; ?Neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies, OMIM:621067

Publications

Created: 1 May 2025, 5:57 p.m.
Last Modified: 1 May 2025, 6:06 p.m.
Panel version: 9.9

Julia Baptista (South East Genomic Laboratory Hub, Synnovis, King's College Hospital)

Green List (high evidence)

Biallelic missense variants of SEL1L and HRD1 (or SYVN1) in 6 children from 3 independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia, and/or ataxia (Wang et al 2024). Hypomorphic variants.

A biallelic SEL1L variant (p. Cys141Tyr) in 5 patients from a consanguineous Slovakian family reported by Weis et al 2024.

A gene-disease association is now described in OMIM.
Sources: Literature
Created: 26 Apr 2025, 6:24 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder

Publications

Created: 26 Apr 2025, 6:24 p.m.

Panel version: 8.243

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Neurodevelopmental disorder with hypotonia, poor growth, dysmorphic facies, and agammaglobulinemia, OMIM:621068
  • ?Neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies, OMIM:621067
Tags
Q2_25_ promote_green Q2_25_ NHS_review
OMIM
602329
Clinvar variants
Variants in SEL1L
Penetrance
None
Publications
Panels with this gene

History Filter Activity

1 May 2025, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: sel1l has been classified as Amber List (Moderate Evidence).

1 May 2025, Gel status: 0

Added Tag, Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_25_ promote_green tag was added to gene: SEL1L. Tag Q2_25_ NHS_review tag was added to gene: SEL1L.

1 May 2025, Gel status: 0

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: SEL1L were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with hypotonia, poor growth, dysmorphic facies, and agammaglobulinemia, OMIM:621068; ?Neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies, OMIM:621067

1 May 2025, Gel status: 0

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: SEL1L were set to 37943610, 37943617

26 Apr 2025, Gel status: 0

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

Julia Baptista (South East Genomic Laboratory Hub, Synnovis, King's College Hospital)

gene: SEL1L was added gene: SEL1L was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: SEL1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEL1L were set to 37943610, 37943617 Phenotypes for gene: SEL1L were set to Neurodevelopmental disorder Review for gene: SEL1L was set to GREEN