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Intellectual disability

Gene: MAP4K4

Amber List (moderate evidence)
MAP4K4 (mitogen-activated protein kinase kinase kinase kinase 4)
EnsemblGeneIds (GRCh38): ENSG00000071054
EnsemblGeneIds (GRCh37): ENSG00000071054
OMIM: 604666, Gene2Phenotype
MAP4K4 is in 4 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: There is sufficient evidence to rate this gene as Green at the next GMS panel update - at least 26 individuals from 21 families reported with Rasopathy-like phenotype (PMID: 37126546). Clinical presentation is varied, but most display symptoms of neurodevelopmental conditions with features overlapping those observed in patients with RASopathies. DD/ID was one of the most common features (ID reported in 8/21 cases).
Created: 6 May 2025, 10:54 a.m. | Last Modified: 6 May 2025, 10:54 a.m.
Panel Version: 9.14
Created: 6 May 2025, 10:54 a.m.
Last Modified: 6 May 2025, 10:54 a.m.
Panel version: 9.14

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The DDG2P confidence category for the disease MAP4K4-related neurodevelopmental disorder with/without congenital anomalies is moderate. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure;decreased gene product level (PMID: 37126546;28518170;36469137).
Created: 26 Sep 2024, 8:30 p.m. | Last Modified: 26 Sep 2024, 8:30 p.m.
Panel Version: 4.10

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
MAP4K4-related neurodevelopmental disorder with/without congenital anomalies

Publications

Created: 26 Sep 2024, 8:30 p.m.
Last Modified: 26 Sep 2024, 8:30 p.m.
Copied from panel: DDG2P v6.1

Irina Ziravecka (BKUS)

Green List (high evidence)

PMID: 37126546 - "a cohort of 26 affected individuals from 21 unrelated families with neurodevelopmental differences, cardiac issues, and CFAs who share a phenotype overlap with RASopathies and harbor a series of rare variants in MAP4K4.
Functional studies in zebrafish showed that MAP4K4 variants caused hypomorphic, LOF, or DN effects."
Sources: Literature
Created: 11 Jul 2023, 9:35 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental differences; multiple congenital anomalies

Publications

Mode of pathogenicity
Other

Created: 11 Jul 2023, 9:35 a.m.

Copied from panel: DDG2P v6.1

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • DD-Gene2Phenotype
  • Literature
Phenotypes
  • MAP4K4-related neurodevelopmental disorder with/without congenital anomalies
  • multiple congenital anomalies
  • neurodevelopmental differences
Tags
Q2_25_ promote_green gene-checked
OMIM
604666
Clinvar variants
Variants in MAP4K4
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

6 May 2025, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_25_ promote_green tag was added to gene: MAP4K4.

6 May 2025, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: map4k4 has been classified as Amber List (Moderate Evidence).

6 May 2025, Gel status: 3

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

Arina Puzriakova (Genomics England Curator)

gene: MAP4K4 was added gene: MAP4K4 was added to Intellectual disability. Sources: Literature,Expert Review Green,DD-Gene2Phenotype gene-checked tags were added to gene: MAP4K4. Mode of inheritance for gene: MAP4K4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MAP4K4 were set to 36469137; 28518170; 37126546; 37126546 Phenotypes for gene: MAP4K4 were set to MAP4K4-related neurodevelopmental disorder with/without congenital anomalies; multiple congenital anomalies; neurodevelopmental differences Mode of pathogenicity for gene: MAP4K4 was set to Other