OGDHL

protein-coding

oxoglutarate dehydrogenase L, the group of Oxoglutarate dehydrogenase family

Gene summary

The protein encoded by this gene is similar to oxoglutarate dehydrogenase (OGDH) of the OGDH complex, which degrades glucose and glutamate. This gene encodes several isoforms, including some that appear to localize to mitochondria. The encoded protein down-regulates the AKT signaling cascade and can suppress the growth of cervical cancer cells. [provided by RefSeq, Dec 2016]

MANE transcript

NM_018245.3

Inheritance

ClinVar variants

P:9U:187B:33

Top phenotype

Yoon-Bellen neurodevelopmental syndrome

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr10:49,734,641-49,762,379

External References & Databases

Ensembl (ENSG00000197444)

Transcript & Mutation Effects

hg38 • Region Span ~27.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Yoon-Bellen neurodevelopmental syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859221

Submitter: Ambry Genetics

Yoon-Bellen neurodevelopmental syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859221

Submitter: Labcorp Genetics (formerly Invitae)

Yoon-Bellen neurodevelopmental syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859221

Submitter: PanelApp Australia

Yoon-Bellen neurodevelopmental syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859221

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Yoon-Bellen neurodevelopmental syndromeAR

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 34800363

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OGDHL variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 152

not providedTotal: 45

Yoon-Bellen neurodevelopmental syndromeTotal: 27

OGDHL-related disorderTotal: 22

not specifiedTotal: 4

DepressionTotal: 1

Abnormal brain morphologyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018245.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		2 clinvar	16 clinvar	6 clinvar	25
missense	1 clinvar	2 clinvar	178 clinvar	10 clinvar	1 clinvar	192
nonsense		2 clinvar	1 clinvar			3
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)		2 clinvar	6 clinvar			8
Total	2	7	187	26	7	229

Highest pathogenic variant AF is 0.00002107999

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018245.3	RefSeq	NP_060715.2	22	MANE Select
ENST00000374103.9	Ensembl	ENSP00000363216.4	22	MANE Select
NM_001143996.2	RefSeq	NP_001137468.1	21	Standard
NM_001143997.2	RefSeq	NP_001137469.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Citrate cycle (TCA cycle) - Homo sapiens (human)
Tryptophan metabolism - Homo sapiens (human)
Lysine degradation - Homo sapiens (human)
Lysine metabolism
TCA cycle

Biological Process

glycolytic process
tricarboxylic acid cycle

Molecular Function

oxoglutarate dehydrogenase (succinyl-transferring) activity
protein binding
thiamine pyrophosphate binding
metal ion binding

Cellular Component

mitochondrion
mitochondrial matrix
oxoglutarate dehydrogenase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374103
Coding exons: 22
Length: 27737
Individuals with no LoFs: 125656
Homozygous LoFs: 0
Heterozygous LoFs: 92
Defined: 125748
p: 0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.497	610	646	0.945	0.0000415	6649
Missense (PolyPhen)		209	227.95	0.91688		2224
Synonymous	-0.00647	261	261	1.00	0.0000170	1963
Loss of Function	3.29	23	47.5	0.484	0.00000212	544

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00061	0.00060	rare
South Asian	0.00033	0.00033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.154

Intolerance Scores

LoFtool: 0.0661
RVIS EVS: -0.54
RVIS percentile EVS: 20.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.600

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium