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Intellectual disability

Gene: MAP4K4

Green List (high 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)

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, imprinted status unknown following NHS Genomic Medicine Service approval.
Created: 12 Mar 2026, 1:33 p.m. | Last Modified: 12 Mar 2026, 1:33 p.m.
Panel Version: 9.299
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: 9.299

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 Green
  • NHS GMS
  • DD-Gene2Phenotype
  • Literature
Phenotypes
  • MAP4K4-related neurodevelopmental disorder with/without congenital anomalies
  • multiple congenital anomalies
  • neurodevelopmental differences
Tags
gene-checked
OMIM
604666
Clinvar variants
Variants in MAP4K4
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

12 Mar 2026, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_25_ promote_green was removed from gene: MAP4K4.

12 Mar 2026, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to MAP4K4. Source Expert Review Green was added to MAP4K4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

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