Intellectual disability
Gene: MYCBP2

MYCBP2 (MYC binding protein 2, E3 ubiquitin protein ligase)
EnsemblGeneIds (GRCh38): ENSG00000005810
EnsemblGeneIds (GRCh37): ENSG00000005810
OMIM: 610392, Gene2Phenotype
MYCBP2 is in 3 panels

2 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now more than 10 unrelated patients with heterozygous MYCBP2 variants and a neurodevelopmental disorder, with ID/GDD being the most consistent feature. Hence, this gene should be promoted to Green at the next update.
Created: 1 Apr 2026, 4:27 p.m. | Last Modified: 1 Apr 2026, 4:27 p.m.

Panel Version: 9.365

PMID: 33875846 Bertoli-Avella et al., 2021
Large WES/WGS cohort. Study detected three de novo variants (one likely affecting splicing and two missense) in three patients with NDD, microcephaly, and seizures. One case presented bilateral bifid thumbs, talipes, and scoliosis, without vaginal or uterine anomalies. No variants details.

PMID: 36200388 AlAbdi et al., 2023
Eight patients (7 male, 1 female) with de novo MYCBP2 variants. Phenotypic spectrum: ID (4/8, moderate to severe), GDD (7/8), corpus callosum thinning / dysgenesis / agenesis (4/5). 2 patients had seizures and 1 had abnormal EEG; 1 patient diagnosed with cone dystrophy, one with retinopathy; 2 patients had hearing loss.

PMID: 41200582 Kostovska et al., 2025
Family with three affected members (mother and 2 sons aged 3yrs and 9 mo) carrying a novel heterozygous MYCBP2 variant NM_015057.5 c.7311del, p.(Leu2438Trpfs*3). Phenotypes: mild intellectual disability, dev delay, speech impairment, facial dysmorphism, microcephaly, seizures (only in the mother). Brain MRI not done.

PMID: 41543631 Pham et al., 2026
Proband with a maternally inherited c.4409dup (p.Leu1470Phefs*7), presented with global developmental delay, autism spectrum disorder (ASD), chronic constipation, sleep disturbances, and aggressive behaviors. Brain MRI showed normal corpus callosum. Mother had generally intact cognition (FSIQ = 103).

MYCBP2 is not yet associated with disease in OMIM (accessed 1st Apr 2026).
Created: 1 Apr 2026, 4:25 p.m. | Last Modified: 1 Apr 2026, 4:34 p.m.

Panel Version: 9.366

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

Created: 1 Apr 2026, 4:25 p.m.
Last Modified: 1 Apr 2026, 4:34 p.m.
Panel version: 9.368

Ludmila Volozonoka (Children's Clinical University Hospital)

Green List (high evidence)

PMID: 36200388 reports eight de novo MYCBP2 variants (two loss-of-function and six missense) in patients presenting with dysmorphism, global developmental delay, varying degrees of intellectual disability, language delay, and ASD. Less common features include corpus callosum dysgenesis and epilepsy.

PMID: 41200582 describes a loss-of-function MYCBP2 variant identified in a mother and her two sons, all exhibiting similar clinical features as in PMID: 36200388.

PMID: 41543631 demonstrates another loss-of-function variant in a proband with NDD, inherited from a mother with mild features (notably subtle executive dysfunction).
The gene is highly constrained of LOF variants in a general population (pLI = 1).
Sources: Literature
Created: 23 Mar 2026, 3:31 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

Created: 23 Mar 2026, 3:31 p.m.

Panel version: 9.346

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Amber

Phenotypes

neurodevelopmental disorder, MONDO:0700092

Tags

Q2_26_promote_green

OMIM

610392

Clinvar variants

Variants in MYCBP2

Penetrance

None

Publications

Panels with this gene

History Filter Activity

2 Apr 2026, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: MYCBP2 were set to 36200388; 41200582; 41543631

1 Apr 2026, Gel status: 2