Intellectual disability syndromic and non-syndromic
Gene: EMC1

EMC1 (ER membrane protein complex subunit 1)
EnsemblGeneIds (GRCh38): ENSG00000127463
EnsemblGeneIds (GRCh37): ENSG00000127463
OMIM: 616846, Gene2Phenotype
EMC1 is in 5 panels

3 reviews

Chern Lim (Victorian Clinical Genetics Services)

Three additional cases with monoallelic inheritance in PMID: 35234901 , patients have developmental delay, truncal hypotonia, seizures and cortical visual impairment.

So far, there are 4 cases of monoallelic inheritance: 3 de novo (PMIDs: 26942288, 35234901) and one likely post-zygotic mosaicism (PMID: 35234901 - variant was absent in mother, father not tested).

All four of these are missense (Gly471Arg, Pro582His, Pro582Arg, Pro584His) and are located in the middle region of the protein, while the AR missense variants are on either ends of the protein.
Created: 9 Aug 2023, 4:01 a.m. | Last Modified: 9 Aug 2023, 4:01 a.m.

Panel Version: 0.5324

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 9 Aug 2023, 4:01 a.m.
Last Modified: 9 Aug 2023, 4:01 a.m.
Panel version: 0.5324

Achchuthan Shanmugasundram (Genomics England)

Green List (high evidence)

Chung et al 2022 (PMID: 35234901) report 3 unrelated children with severe to profound developmental delay, truncal hypotonia, seizures and cortical visual impairment. A c.1745C > A; p.Pro582His (de novo) variant in EMC1 was found in 2 of the individuals. The other child had EMC1 c.1745C > G; p.Pro582Arg (mosaic; not inherited from mother, father deceased). Variants were identified by WES and confirmed by Sanger sequencing. In a Drosophila model the identified variants didn't rescue the lethality of a null allele. They also found variations in dosage of the wild-type EMC1, specifically in glia, lead to pupal lethality.

As there are three additional unrelated cases of monoallelic variants in patients with an intellectual disability phenotype reported now, the mode of inheritance should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'
Created: 1 Mar 2023, 2:35 p.m. | Last Modified: 1 Mar 2023, 2:35 p.m.

Panel Version: 0.5179

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

35234901

Created: 1 Mar 2023, 2:35 p.m.
Last Modified: 1 Mar 2023, 2:35 p.m.
Panel version: 0.5179

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Four unrelated families with bi-allelic variants in this gene reported. Single individual with heterozygous variant: insufficient evidence at present for mono allelic variants causing disease.
Sources: Expert list
Created: 2 Feb 2020, 4:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebellar atrophy, visual impairment, and psychomotor retardation, MIM# 616875

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 2 Feb 2020, 4:01 a.m.

Panel version: 0.1920

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

Expert Review Green
Expert list

Phenotypes

Cerebellar atrophy, visual impairment, and psychomotor retardation, MIM# 616875

OMIM

616846

Clinvar variants

Variants in EMC1

Penetrance

None

Publications

Panels with this gene