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Intellectual disability

Gene: CLEC16A

Green List (high evidence)
CLEC16A (C-type lectin domain containing 16A)
EnsemblGeneIds (GRCh38): ENSG00000038532
EnsemblGeneIds (GRCh37): ENSG00000038532
OMIM: 611303, Gene2Phenotype
CLEC16A is in 1 panel

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green 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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 26 Sep 2024, 2:57 p.m.
Last Modified: 26 Sep 2024, 2:57 p.m.
Panel version: 7.41

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Heterozygous CLEC16A variants have been identified as a genetic risk factor for several autoimmune disorders and for Parkinson disease (PMID: 37175930). PMID: 36538041 reports the neurological effect of homozygous terminating CLEC16A variants in two families. In family 1, the first child died at 5 months, he had progressive microcephaly, failure to thrive and cranial CT showed brain atrophy, dilatation of both central and peripheral liquor spaces, hypoplasia of the corpus callosum (no genetic testing was done), the third pregnancy was terminated (17 weeks of gestation) after prenatal ultrasound showed ventriculomegaly, agenesis of corpus callosum (no genetic testing was done), the fourth pregnancy was also terminated (22 weeks of gestation) as the prenatal ultrasound showed agenesis of corpus callosum. This fetus was homozygous for NM_001243403.1(CLEC16A):c.2062 + 5G > A, RT-PRC showed that this variant resulted in the deletion of exon 19 and a frame shift. Both parents and an unaffected sibling were heterozygous for this variant. In family 2, a single affected child was homozygous for NM_001243403.1(CLEC16A):c.-4_12del, p.Met1fs*. This child had progressive microcephaly, failure to thrive, severe global developmental delay, global brain atrophy and died at 6 years. There is no genetic data from the parents or unaffected siblings in Family 2. PMID: 37175930, also presents zebrafish experiments, where mutagenesis of
clec16a by CRISPR–Cas9 resulted in accumulated acidic/phagolysosome compartments, in neurons
and microglia, and dysregulated mitophagy. This was rescued by wild type CLEC16A, but not by the C-terminal truncated variant. The authors conclude that dysregulation of CLEC16A-mediated endosomal sorting is associated with neurodegeneration.
Created: 20 Mar 2024, 10:01 a.m. | Last Modified: 20 Mar 2024, 10:01 a.m.
Panel Version: 5.502
Comment on list classification: There is enough evidence for this gene to be green on this panel.
Created: 19 Mar 2024, 4:25 p.m. | Last Modified: 19 Mar 2024, 4:25 p.m.
Panel Version: 5.502

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 19 Mar 2024, 4:25 p.m.
Last Modified: 19 Mar 2024, 4:25 p.m.
Panel version: 5.502

Dmitrijs Rots (Children's Clinical University Hospital)

Green List (high evidence)

Two independent cases reported PMID: 36538041with biallelic variants and functional evidence. Sufficient for the green rating.
Sources: Literature
Created: 10 Nov 2023, 4:52 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
severe neurodevelopmental disorder including microcephaly, brain atrophy, corpus callosum dysgenesis, and growth retardation

Publications

Created: 10 Nov 2023, 4:52 p.m.

Panel version: 5.337

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • severe neurodevelopmental disorder including microcephaly, brain atrophy, corpus callosum dysgenesis, and growth retardation
Tags
gene-checked
OMIM
611303
Clinvar variants
Variants in CLEC16A
Penetrance
Complete
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: CLEC16A.

26 Sep 2024, Gel status: 3

Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q1_24_promote_green was removed from gene: CLEC16A.

26 Sep 2024, Gel status: 3

Added New Source, Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source NHS GMS was added to CLEC16A. Source Expert Review Green was added to CLEC16A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

27 Mar 2024, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q1_24_promote_green tag was added to gene: CLEC16A.

19 Mar 2024, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: clec16a has been classified as Amber List (Moderate Evidence).

19 Mar 2024, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: CLEC16A were set to 36538041

19 Mar 2024, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: CLEC16A were set to PMID: 36538041

19 Mar 2024, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: clec16a has been classified as Amber List (Moderate Evidence).

10 Nov 2023, Gel status: 0

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

Dmitrijs Rots (Children's Clinical University Hospital)

gene: CLEC16A was added gene: CLEC16A was added to Intellectual disability - microarray and sequencing. Sources: Literature Mode of inheritance for gene: CLEC16A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLEC16A were set to PMID: 36538041 Phenotypes for gene: CLEC16A were set to severe neurodevelopmental disorder including microcephaly, brain atrophy, corpus callosum dysgenesis, and growth retardation Penetrance for gene: CLEC16A were set to Complete Review for gene: CLEC16A was set to GREEN