L2HGDH

L-2-hydroxyglutarate dehydrogenase, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 14:50237563-50312229

Previous symbols: [ "C14orf160" ]

Links

ENSG00000087299 ∙ NCBI:79944 ∙ OMIM:609584 ∙ HGNC:20499 ∙ Uniprot:Q9H9P8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• L-2-hydroxyglutaric aciduria (Definitive), mode of inheritance: AR
• L-2-hydroxyglutaric aciduria (Definitive), mode of inheritance: AR
• L-2-hydroxyglutaric aciduria (Strong), mode of inheritance: AR
• L-2-hydroxyglutaric aciduria (Supportive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
L-2-hydroxyglutaric aciduria	AR	Biochemical; Oncologic	A low lysine diet has been reported as resulting in clinical and biochemical improvement; An increased risk of cerebral neoplasms has been reported, and awareness may lead to early detection and treatment	Biochemical; Neurologic; Oncologic	6787330; 1642474; 7609438; 7609437; 9860123; 10399870; 15548604; 15385440; 15824270; 18931888; 21937992; 22241392; 22353300; 22459673

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the L2HGDH gene.

• L-2-hydroxyglutaric_aciduria (233 variants)
• Inborn_genetic_diseases (61 variants)
• not_provided (37 variants)
• not_specified (24 variants)
• L2HGDH-related_disorder (9 variants)
• Abnormality_of_metabolism/homeostasis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the L2HGDH gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024884.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	2	50	2	55
missense	5	8	123	12	1	149
nonsense	8	1				9
start loss	1					1
frameshift	7	1	2			10
splice donor/acceptor (+/-2bp)	5	5	2			12
Total	26	16	129	62	3

Highest pathogenic variant AF is 0.0000359916

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
L2HGDH	protein_coding	protein_coding	ENST00000267436	10	74986

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000422	0.992	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.425	235	254	0.925	0.0000124	2972
Missense in Polyphen		97	108.8	0.89156		1340
Synonymous	0.705	80	88.4	0.905	0.00000401	935
Loss of Function	2.34	11	23.1	0.475	0.00000129	272

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000383	0.000383
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000326	0.000326
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Pathway: Butanoate metabolism - Homo sapiens (human);The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Interconversion of 2-oxoglutarate and 2-hydroxyglutarate;Pyruvate metabolism and Citric Acid (TCA) cycle;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine (Consensus)

Recessive Scores

• pRec: 0.159

Intolerance Scores

• loftool: 0.360
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.45

Haploinsufficiency Scores

• pHI: 0.391
• hipred: N
• hipred_score: 0.465
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.750

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: L2hgdh
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: 2-oxoglutarate metabolic process;cellular protein metabolic process;oxidation-reduction process
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane;integral component of mitochondrial inner membrane
• Molecular function: (S)-2-hydroxy-acid oxidase activity;2-hydroxyglutarate dehydrogenase activity