Yoon-Bellen neurodevelopmental syndrome

Summary

Yoon-Bellen neurodevelopmental syndrome (MONDO:0859221) is a disease caused by OGDHL (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: OGDHL (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Yoon-Bellen neurodevelopmental syndrome
Mondo ID	MONDO:0859221
OMIM	619701
DOID	DOID:0070468
UMLS	C5562066
MedGen	1794276
Is cancer (heuristic)	no

Data availability: 26 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › Yoon-Bellen neurodevelopmental syndrome

Related subtypes (20): intellectual disability, microcephaly, Williams syndrome, Aicardi syndrome, Hao-Fountain syndrome, toluene embryopathy, alternating hemiplegia, atypical Rett syndrome, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, complex neurodevelopmental disorder, Mendelian neurodevelopmental disorder, TCF7L2-related neurodevelopmental disorder, neurodevelopmental disorder with seizures and brain abnormalities, neurodevelopmental disorder with microcephaly, hypotonia, and absent language, neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss, neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies, neurodevelopmental disorder with parkinsonism or other movement abnormalities, neurodevelopmental disorder with seizures and impaired intellectual and language development, Ebstein-Bezieau neurodevelopmental syndrome, Luo-Agrawal neurodevelopmental syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

26 retrieved; paginated sample, class counts are floors:

17 uncertain significance, 6 likely pathogenic, 2 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1334178	NM_018245.3(OGDHL):c.2018G>A (p.Arg673Gln)	OGDHL	Pathogenic	no assertion criteria provided
1334179	NM_018245.3(OGDHL):c.1464T>C (p.Val488=)	OGDHL	Pathogenic	no assertion criteria provided
1334181	NM_018245.3(OGDHL):c.895A>G (p.Arg299Gly)	OGDHL	Likely pathogenic	criteria provided, single submitter
2503805	NM_018245.3(OGDHL):c.2140+1G>A	OGDHL	Likely pathogenic	criteria provided, single submitter
3065905	NM_018245.3(OGDHL):c.1862-2A>G	OGDHL	Likely pathogenic	criteria provided, single submitter
402144	NM_018245.3(OGDHL):c.2333C>T (p.Ser778Leu)	OGDHL	Likely pathogenic	criteria provided, single submitter
4072296	NM_018245.3(OGDHL):c.1685del (p.Asp562fs)	OGDHL	Likely pathogenic	criteria provided, single submitter
4293918	NM_018245.3(OGDHL):c.1135C>T (p.Gln379Ter)	OGDHL	Likely pathogenic	criteria provided, single submitter
2640463	NM_018245.3(OGDHL):c.103G>A (p.Gly35Arg)	OGDHL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1334177	NM_018245.3(OGDHL):c.2554C>G (p.Pro852Ala)	OGDHL	Uncertain significance	no assertion criteria provided
1334180	NM_018245.3(OGDHL):c.730C>T (p.Arg244Trp)	OGDHL	Uncertain significance	no assertion criteria provided
2203835	NM_018245.3(OGDHL):c.2273G>A (p.Arg758Gln)	OGDHL	Uncertain significance	criteria provided, multiple submitters, no conflicts
2572542	NM_018245.3(OGDHL):c.2050C>T (p.Arg684Cys)	OGDHL	Uncertain significance	criteria provided, multiple submitters, no conflicts
3067890	NM_018245.3(OGDHL):c.1984G>A (p.Gly662Arg)	OGDHL	Uncertain significance	criteria provided, single submitter
3068109	NM_018245.3(OGDHL):c.1733G>C (p.Gly578Ala)	OGDHL	Uncertain significance	criteria provided, single submitter
3340506	NM_018245.3(OGDHL):c.1552C>T (p.His518Tyr)	OGDHL	Uncertain significance	criteria provided, single submitter
3340507	NM_018245.3(OGDHL):c.1262C>A (p.Thr421Asn)	OGDHL	Uncertain significance	criteria provided, single submitter
3376232	NM_018245.3(OGDHL):c.1402G>C (p.Glu468Gln)	OGDHL	Uncertain significance	criteria provided, multiple submitters, no conflicts
3409847	NM_018245.3(OGDHL):c.795T>G (p.Phe265Leu)	OGDHL	Uncertain significance	criteria provided, multiple submitters, no conflicts
3595533	NM_018245.3(OGDHL):c.2170C>T (p.Pro724Ser)	OGDHL	Uncertain significance	criteria provided, single submitter
3595535	NM_018245.3(OGDHL):c.1051C>T (p.Arg351Trp)	OGDHL	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891876	NM_018245.3(OGDHL):c.794T>G (p.Phe265Cys)	OGDHL	Uncertain significance	criteria provided, single submitter
4072285	NM_018245.3(OGDHL):c.1861+14A>T	OGDHL	Uncertain significance	criteria provided, single submitter
4279771	NM_018245.3(OGDHL):c.2604G>T (p.Gln868His)	OGDHL	Uncertain significance	criteria provided, single submitter
4279772	NM_018245.3(OGDHL):c.2150T>G (p.Leu717Arg)	OGDHL	Uncertain significance	criteria provided, single submitter
4292657	NM_018245.3(OGDHL):c.1721C>A (p.Ser574Tyr)	OGDHL	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
OGDHL	Strong	Autosomal recessive	Yoon-Bellen neurodevelopmental syndrome	4

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
OGDHL	HGNC:25590	ENSG00000197444	Q9ULD0	2-oxoglutarate dehydrogenase-like, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OGDHL	2-oxoglutarate dehydrogenase-like, mitochondrial	2-oxoglutarate dehydrogenase (E1-like) component of the 2-oxoglutarate dehydrogenase multienzyme complex (OGDHC) which mediates the decarboxylation of alpha-ketoglutarate in the tricarboxylic acid cycle.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OGDHL	Enzyme (other)	yes	1.2.1.105	DH_E1, Transketolase-like_Pyr-bd, 2oxoglutarate_DH_E1

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adult mammalian kidney	1
right hemisphere of cerebellum	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OGDHL	186	broad	marker	adult mammalian kidney, right lobe of liver, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OGDHL	2,138

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OGDHL	Q9ULD0	90.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
2-oxoglutarate metabolic process	1	936.2×	0.003	OGDHL
tricarboxylic acid cycle	1	510.7×	0.003	OGDHL
glycolytic process	1	383.0×	0.003	OGDHL

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
OGDHL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
OGDHL	1.2.1.105	2-oxoglutarate dehydrogenase system

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	OGDHL
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
OGDHL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.