1. Panels
  2. Intellectual disability
  3. MARK2
Genes in panel
Prev Next
Regions in panel
Prev Next

Intellectual disability

Gene: MARK2

Green List (high evidence)
MARK2 (microtubule affinity regulating kinase 2)
EnsemblGeneIds (GRCh38): ENSG00000072518
EnsemblGeneIds (GRCh37): ENSG00000072518
OMIM: 600526, Gene2Phenotype
MARK2 is in 2 panels

3 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted 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
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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: As reviewed by Zornitza Stark, 31 individuals were reported with intellectual disability/ developmental delay and with monoallelic MARK2 variants. ID/ DD was severe in seven, moderate in two, mild and/or borderline in four and unspecified in 17. In addition, functional evidence is also available.

This gene can therefore be promoted to green rating in the next GMS update.
Created: 14 Nov 2024, 11:59 a.m. | Last Modified: 14 Nov 2024, 11:59 a.m.
Panel Version: 8.28
Comment on phenotypes: This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Created: 14 Nov 2024, 11:46 a.m. | Last Modified: 14 Nov 2024, 11:46 a.m.
Panel Version: 8.27

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

Publications

Created: 14 Nov 2024, 11:44 a.m.
Last Modified: 14 Nov 2024, 11:44 a.m.
Panel version: 8.25

Zornitza Stark (Australian Genomics)

Green List (high evidence)

31 individuals with autism spectrum disorder (30/31), intellectual disability/developmental delay (100%), motor delay (62%), speech-language problems (100%), seizure/epilepsy (46%), behaviour disorders (ADHD, aggression, anxiety)(74%), and distinctive facial features (narrow face, abnormal or broad forehead, downslanting palpebral fissures, and large or dysplastic ears).

WES/WGS identified 25 LOF and 6 missense variants in MARK2 gene (Microtubule affinity-regulating kinase 2) which contributes to establishing neuronal polarity and developing dendritic spines. LOF variants were de novo (16/25), inherited (4/25), or unk (5/25). All 6 missense variants were de novo and clustered in the kinase or KA1 domains.

The mRNA and protein expression of MARK2 in PBMCs were significantly lower in affected individuals with LOF variants than in the control group. In vitro expression assay of missense variants supported the effect of MARK2 loss. Proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs) showed MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and disorganization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behaviour. Through the use of RNA sequencing (RNA-seq) and lithium treatment, they linked MARK2 loss to downregulation of the WNT/β-catenin signaling pathway and identified lithium as a potential drug for treating MARK2-associated ASD.
Sources: Literature
Created: 11 Nov 2024, 6:09 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder MONDO:0700092

Publications

Created: 11 Nov 2024, 6:09 a.m.

Panel version: 8.16

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • neurodevelopmental disorder, MONDO:0700092
  • intellectual disability, MONDO:0001071
Tags
gene-checked
OMIM
600526
Clinvar variants
Variants in MARK2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Mar 2025, Gel status: 3

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag gene-checked tag was added to gene: MARK2.

25 Feb 2025, Gel status: 3

Removed Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_24_promote_green was removed from gene: MARK2.

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 MARK2. Source Expert Review Green was added to MARK2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

14 Nov 2024, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: mark2 has been classified as Amber List (Moderate Evidence).

14 Nov 2024, Gel status: 0

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: MARK2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

14 Nov 2024, Gel status: 0

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_24_promote_green tag was added to gene: MARK2.

14 Nov 2024, Gel status: 0

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: MARK2 were changed from Neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

11 Nov 2024, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: MARK2 was added gene: MARK2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: MARK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MARK2 were set to 39419027; 39436150 Phenotypes for gene: MARK2 were set to Neurodevelopmental disorder MONDO:0700092 Review for gene: MARK2 was set to GREEN