Intellectual disability
Gene: MAPKAPK5

MAPKAPK5 (mitogen-activated protein kinase-activated protein kinase 5)
EnsemblGeneIds (GRCh38): ENSG00000089022
EnsemblGeneIds (GRCh37): ENSG00000089022
OMIM: 606723, Gene2Phenotype
MAPKAPK5 is in 4 panels

4 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 24 Feb 2025, 6:15 p.m. | Last Modified: 24 Feb 2025, 6:15 p.m.

Panel Version: 8.97

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 24 Feb 2025, 6:15 p.m.
Last Modified: 24 Feb 2025, 6:15 p.m.
Panel version: 8.97

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (6 unrelated families) for the promotion of this gene to green rating in the next GMS update.
Created: 24 Jul 2024, 11:53 a.m. | Last Modified: 24 Jul 2024, 11:53 a.m.

Panel Version: 6.75

PMID:35575217 reported a 19-month-old boy of Italian descent with neurocardiofaciodigital syndrome (NCFD). He had global developmental delay and his digit abnormalities include short fingers, broad big toes and marked toenail hypoplasia/dysplasia. He was identified with a pathogenic homozygous nonsense variant in MAPKAPK5 gene (p.Arg394Ter).

PMID:36581449 reported three unrelated individuals (one each from Pakistani, Palestinian - Arab and Egyptian descent) with NCFD. All of them had varying degrees of developmental delay and intellectual disability (one each with profound, severe and moderate ID), and digit abnormalities. They were all identified with homozygous MAPKAPK5 variant (p.Leu224Cysfs*4, p.Gln437Ter and p.Gly107Val ).

This gene has been associated with relevant phenotypes in OMIM (MIM #619869) and Gene2Phenotype (with 'strong' rating on the DD panel).
Created: 24 Jul 2024, 11:45 a.m. | Last Modified: 24 Jul 2024, 11:45 a.m.

Panel Version: 6.71

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurocardiofaciodigital syndrome, OMIM:619869

Publications

Created: 24 Jul 2024, 11:45 a.m.
Last Modified: 24 Jul 2024, 11:45 a.m.
Panel version: 6.71

Arina Puzriakova (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark. Rating Amber, awaiting further cases (added watchlist tag)

- PMID: 33442026 report on 2 unrelated families with a comparable phenotype including severe GDD, who harbour different homozygous truncating variants in MAPKAPK5. Some functional evidence indicating the variants impact expression and function of MAPKAPK5 protein.

MAPKAPK5 is not yet associated with any phenotype in OMIM (last edited on 06/04/2016) but has a 'probable' disease confidence rating for 'MAPKAPK5-associated syndrome with synpolydactyly' in Gene2Phenotype.
Created: 30 Apr 2021, 9:23 a.m. | Last Modified: 30 Apr 2021, 9:23 a.m.

Panel Version: 3.1045

Created: 30 Apr 2021, 9:23 a.m.
Last Modified: 30 Apr 2021, 9:23 a.m.
Panel version: 3.1045

Zornitza Stark (Australian Genomics)

Green List (high evidence)

3 individuals from 2 families with severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet. Exome sequencing identified different homozygous truncating variants in MAPKAPK5 in both families, segregating with disease and unaffected parents as carriers.

Patient-derived cells showed no expression of MAPKAPK5 protein isoforms and reduced levels of the MAPKAPK5-interacting protein ERK3. F-actin recovery after latrunculin B treatment was found to be less efficient in patient-derived fibroblasts than in control cells, supporting a role of MAPKAPK5 in F-actin polymerization.

Borderline Amber/Green but high impact variants and a distinctive phenotype with some functional data.
Sources: Literature
Created: 19 Apr 2021, 8:55 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Developmental delay, variable brain anomalies, congenital heart defects, dysmorphism

Publications

3344202

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

Created: 19 Apr 2021, 8:55 a.m.

Panel version: 3.1018

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS

Phenotypes

Neurocardiofaciodigital syndrome, OMIM:619869

OMIM

606723

Clinvar variants

Variants in MAPKAPK5

Penetrance

None

Publications

Panels with this gene

History Filter Activity

25 Feb 2025, Gel status: 3

Removed Tag, Removed Tag

Sarah Leigh (Genomics England Curator)

Tag watchlist was removed from gene: MAPKAPK5. Tag Q3_24_promote_green was removed from gene: MAPKAPK5.

24 Feb 2025, Gel status: 3

Added New Source, Added New Source, Status Update

Sarah Leigh (Genomics England Curator)

Source NHS GMS was added to MAPKAPK5. Source Expert Review Green was added to MAPKAPK5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

24 Jul 2024, Gel status: 2