1. Panels
  2. Intellectual disability syndromic and non-syndromic
  3. SEL1L
Genes in panel
Prev Next
STRs in panel
Prev Next
Regions in panel
Prev Next

Intellectual disability syndromic and non-syndromic

Gene: SEL1L

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

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with hypotonia, poor growth, dysmorphic facies, and agammaglobulinaemia, MIM# 621068; Neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies, MIM# 621067

Created: 3 Feb 2025, 4:07 a.m.
Last Modified: 3 Feb 2025, 4:07 a.m.
Panel version: 1.50

Sarah Pantaleo (Victorian Clinical Genetics Services)

Green List (high evidence)

Wang paper PMID: 37943610

SEL1L protein is involved in the SEL1L-HRD1 endoplasmic reticulum (ER)-associated degradation.

Report two biallelic missense variants in SEL1L in six children from three independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia and/or ataxia (termed ERAD-associated neurodevelopment disorder with onset in infancy (ENDI). The variants were hypomorphic and impaired ERAD function.

Identified by WES. Parents heterozygous and asymptomatic. P.(Gly585Asp) in Patient 1, p.(Met528Arg) in Patients 2 and 3 (siblings).

All variants cause substrate accumulation. The extent of substrate accumulation in knockin cells was modest compared to those in knockout cells, pointing to a hypomorphic nature.

They also had a variant in HRD1.



Weis paper PMID: 37943617

Third variant p.(Cys141Tyr), biallelic, causing premature death in five patients from a consanguineous family with early-onset neurodevelopmental disorders and agammaglobulinaemia due to severe SEL1L-HRD1 ERAD dysfunction.

This variant appears to have a more severe outcome, exhibiting B cell depletion and agammaglobulinaemia, causing the most severe dysfunction among all of the variants described by this group so far. They postulate that functionality of SEL1L-HRD1 ERAD is inversely correlated with disease severity in humans.

Their symptoms were dev delay, neurological disorder and agammaglobulinaemia in childhood. Along with severe axial hypotonia, short stature and microcephaly.

“Not a complete loss-of-function variant”.
Sources: Literature
Created: 7 Dec 2023, 1:37 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder, MONDO:0700092, SEL1L-related

Publications

Created: 7 Dec 2023, 1:37 a.m.

Panel version: 0.5627

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Neurodevelopmental disorder with hypotonia, poor growth, dysmorphic facies, and agammaglobulinaemia, MIM# 621068
  • Neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies, MIM# 621067
OMIM
602329
Clinvar variants
Variants in SEL1L
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

3 Feb 2025, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: SEL1L were changed from Neurodevelopmental disorder, MONDO:0700092, SEL1L-related to Neurodevelopmental disorder with hypotonia, poor growth, dysmorphic facies, and agammaglobulinaemia, MIM# 621068; Neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies, MIM# 621067

7 Dec 2023, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: sel1l has been classified as Green List (High Evidence).

7 Dec 2023, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: sel1l has been classified as Green List (High Evidence).

7 Dec 2023, Gel status: 0

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

Sarah Pantaleo (Victorian Clinical Genetics Services)

gene: SEL1L was added gene: SEL1L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: SEL1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEL1L were set to PMID: 37943610; PMID: 37943617 Phenotypes for gene: SEL1L were set to Neurodevelopmental disorder, MONDO:0700092, SEL1L-related Penetrance for gene: SEL1L were set to Complete Review for gene: SEL1L was set to GREEN