Intellectual disability
Gene: OGDHL

OGDHL (oxoglutarate dehydrogenase like)
EnsemblGeneIds (GRCh38): ENSG00000197444
EnsemblGeneIds (GRCh37): ENSG00000197444
OMIM: 617513, Gene2Phenotype
OGDHL is in 6 panels

3 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: This gene should remain Green for Intellectual disability. There is strong evidence for the association between OGDHL and Yoon-Bellen neurodevelopmental syndrome. However, the phenotype is highly heterogeneous, and care should be taken not to attribute all clinical symptoms to OGDHL dysfunction.
Created: 24 Sep 2025, 2:17 p.m. | Last Modified: 24 Sep 2025, 2:17 p.m.

Panel Version: 9.99

As reviewed by Arina Puzriakova, there are at least 10 individuals from 9 unrelated families with biallelic variants in OGDHL (PMIDs: 28017472; 34800363). The individuals present with a complex neurodevelopmental disorder, also known as Yoon-Bellen syndrome. The phenotype is highly variable between the cases and includes developmental delay / intellectual disability.

PMID: 38031187 Lin et al. 2023 - authors re-evaluate the evidence for the association between Yoon-Bellen neurodevelopmental syndrome and the OGDHL gene. The article reports further 14 individuals from 12 unrelated, diverse families, with biallelic OGDHL variants. Patients presented with a range of heterogeneous symptoms: hypotonia (9/14), short stature and variable dysmorphic facial features (each 8/14), failure to thrive (7/14), developmental delay/intellectual disability (9/14), seizures (4/14), hearing loss (4/14), and microcephaly (3/14). Due to the highly variable phenotype, authors propose 3 possible hypotheses: ‘biallelic OGDHL variants lead to a highly variable monogenic disorder, variants in OGDHL are following a complex pattern of inheritance, or they may not be causative at all’.

In total, 17/21 families reported in the above articles have history of consanguinity. In most cases, additional likely pathogenic mutations were discovered in other genes, which complicates the phenotypic understanding.

Functional evidence: A zebrafish knockout of Ogdhl (78% identical gene ortholog) resulted in a range of phenotypes: smaller head, eye, and body, and heart edema. No seizure manifestation, visual impairment, or hearing deficiencies were observed. Authors note elevated neuronal cell death in the eye, hindbrain, and spinal cord of knockout animals. The phenotype was rescued by injection of human OGDHL. Moreover, OGDHL, OGDH, and DHTKD1 are isoenzymes – through double and triple gene knockouts, authors provide evidence indicating a complex compensatory relationship (PMID: 38031187).

This gene should remain Green for Intellectual disability. There is strong evidence for the association between OGDHL and Yoon-Bellen neurodevelopmental syndrome. However, care should be taken not to attribute all clinical symptoms to OGDHL dysfunction.
Created: 24 Sep 2025, 2:16 p.m. | Last Modified: 10 Oct 2025, 1:12 p.m.

Panel Version: 9.122

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Yoon-Bellen neurodevelopmental syndrome, MONDO:0859221

Publications

Created: 24 Sep 2025, 2:16 p.m.
Last Modified: 10 Oct 2025, 1:12 p.m.
Panel version: 9.99

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 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Created: 30 Jan 2023, 5:50 p.m. | Last Modified: 30 Jan 2023, 5:50 p.m.

Panel Version: 4.53

Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote to Green at the next GMS panel update.

The NSRP1 gene is not yet associated with any phenotype in OMIM but has a 'moderate' disease confidence rating in G2P for 'OGDHL-related neurodevelopmental disorder with seizures, hearing loss and gait ataxia'.

At least 10 individuals from 9 unrelated families identified with biallelic variants in this gene (PMIDs: 28017472; 34800363). Main clinical features include mild-to-severe DD/ID (9/10), seizures (5/10), gait ataxia (5/10), profound bilateral sensorineural hearing loss (4/10), spasticity (3/10).
Created: 1 Aug 2022, 12:38 p.m. | Last Modified: 1 Aug 2022, 12:38 p.m.

Panel Version: 3.1643

Created: 1 Aug 2022, 12:38 p.m.
Last Modified: 1 Aug 2022, 12:38 p.m.
Panel version: 4.53

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing
loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum.

Homozygous and compound heterozygous variants reported. Variant types reported include missense, PTCs and a synonymous variant that was shown to affect splicing.

Functional studies with a CRISPR-Cas9-mediated tissue knockout with cDNA rescue system showed that the missense variants result in loss-of-function.
Sources: Literature
Created: 4 Dec 2021, 2:55 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder featuring epilepsy, hearing loss and visual impairment

Publications

34800363

Created: 4 Dec 2021, 2:55 a.m.

Panel version: 3.1478

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS

Phenotypes

Yoon-Bellen neurodevelopmental syndrome, OMIM:619701

Tags

gene-checked

OMIM

617513

Clinvar variants

Variants in OGDHL

Penetrance

None

Publications

Panels with this gene

History Filter Activity

19 Dec 2025, Gel status: 3

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

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

30 Jan 2023, Gel status: 3