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Intellectual disability

Gene: MCM3AP

Green List (high evidence)

MCM3AP (minichromosome maintenance complex component 3 associated protein)
EnsemblGeneIds (GRCh38): ENSG00000160294
EnsemblGeneIds (GRCh37): ENSG00000160294
OMIM: 603294, Gene2Phenotype
MCM3AP is in 5 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants
Created: 30 Jun 2020, 4:33 p.m. | Last Modified: 30 Jun 2020, 4:33 p.m.
Panel Version: 3.123

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by external expert and reviewed by curation team: Sufficient evidence has been provided by the external expert review for this gene to be rated green. There are >3 cases of unrelated patients with variants in MCM3AP who have ID. The gene is associated with a phenotype on OMIM but not Gene2Phenotype.
Created: 18 Feb 2019, 3:30 p.m.

Konstantinos Varvagiannis (Other)

I don't know

Biallelic mutations in MCM3AP cause Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (MIM 618124).

All relevant publications [PMIDs: 24123876, 28633435 (first detailed description of a series of patients with functional studies), 28969388, 29982295) are summarized in OMIM.

Overall more than 18 patients from 10 families and at least 8 pathogenic variants have been reported.

Apart from abnormal motor development which may be associated with the sensorimotor neuropathy, intellectual disability was a feature in several individuals (although not a universal one).

Some patients were initially evaluated for their ID while investigations for the neuropathy may be conducted late (as evident in PMID: 28633435).

MCM3AP is included in gene panels for intellectual disability offered by diagnostic laboratories.

As a result, this gene can be considered for inclusion in the ID panel as amber or green (depending on its relevance to the specific panel).
Sources: Literature
Created: 6 Dec 2018, 7:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (MIM 618124)

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, 618124
OMIM
603294
Clinvar variants
Variants in MCM3AP
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

1 Jul 2020, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295; 32202298

30 Jun 2020, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295; 32202298

30 Jun 2020, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295; 32202298

30 Jun 2020, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295

18 Feb 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: mcm3ap has been classified as Green List (High Evidence).

18 Feb 2019, Gel status: 0

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: MCM3AP were changed from Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (MIM 618124) to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, 618124

6 Dec 2018, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: MCM3AP was added gene: MCM3AP was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: MCM3AP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295 Phenotypes for gene: MCM3AP were set to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (MIM 618124) Penetrance for gene: MCM3AP were set to Complete Review for gene: MCM3AP was set to AMBER gene: MCM3AP was marked as current diagnostic