L2HGDH

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

Basic information

Region (hg38): 14:50237562-50312229

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 (198 variants)
• not provided (46 variants)
• not specified (26 variants)
• Inborn genetic diseases (19 variants)
• Abnormality of metabolism/homeostasis (1 variants)
• L2HGDH-related condition (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	34	2	37
missense	3	6	97	5	1	112
nonsense	6	1				7
start loss	1					1
frameshift	7	1	1			9
inframe indel				1		1
splice donor/acceptor (+/-2bp)	2	3	1			6
splice region		1	7	5	3	16
non coding			2	17	17	36
Total	19	11	102	57	20

Highest pathogenic variant AF is 0.0000131

Variants in L2HGDH

This is a list of pathogenic ClinVar variants found in the L2HGDH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-50237660-ATGT-A			Likely benign (May 01, 2022)
14-50246961-T-G			Benign (May 12, 2021)
14-50247067-A-G		L-2-hydroxyglutaric aciduria	Likely benign (Apr 19, 2019)
14-50247071-C-A		L-2-hydroxyglutaric aciduria	Uncertain significance (Aug 04, 2023)
14-50247074-T-C		L-2-hydroxyglutaric aciduria	Uncertain significance (Apr 07, 2022)
14-50247078-G-T		L-2-hydroxyglutaric aciduria • Inborn genetic diseases	Uncertain significance (Sep 13, 2023)
14-50247097-T-C		L-2-hydroxyglutaric aciduria	Benign (Jan 22, 2024)
14-50247108-C-G		L-2-hydroxyglutaric aciduria	Uncertain significance (Jun 12, 2022)
14-50247111-T-C		L-2-hydroxyglutaric aciduria	Uncertain significance (Oct 13, 2022)
14-50247126-CA-C		L-2-hydroxyglutaric aciduria	Uncertain significance (Oct 02, 2021)
14-50247128-G-A		L-2-hydroxyglutaric aciduria	Uncertain significance (-)
14-50247138-C-T		L-2-hydroxyglutaric aciduria	Uncertain significance (Apr 08, 2022)
14-50247150-G-C		L-2-hydroxyglutaric aciduria	Uncertain significance (Apr 08, 2023)
14-50247165-C-T		L-2-hydroxyglutaric aciduria	Uncertain significance (Sep 27, 2022)
14-50247174-C-T		L-2-hydroxyglutaric aciduria	Uncertain significance (Oct 04, 2023)
14-50247179-C-T		L-2-hydroxyglutaric aciduria	Uncertain significance (Dec 02, 2021)
14-50247181-T-C		not specified • L-2-hydroxyglutaric aciduria	Conflicting classifications of pathogenicity (Dec 01, 2023)
14-50247183-C-T		L-2-hydroxyglutaric aciduria	Uncertain significance (Apr 05, 2023)
14-50247192-C-T		L-2-hydroxyglutaric aciduria	Uncertain significance (Oct 24, 2022)
14-50247220-A-G		L-2-hydroxyglutaric aciduria	Likely benign (Nov 01, 2022)
14-50247222-C-T		not specified	Uncertain significance (Apr 23, 2015)
14-50247237-T-C		L-2-hydroxyglutaric aciduria	Uncertain significance (Jul 05, 2019)
14-50247240-C-G		L-2-hydroxyglutaric aciduria	Uncertain significance (Jan 11, 2022)
14-50247249-G-C		Inborn genetic diseases	Uncertain significance (Jan 11, 2023)
14-50247250-G-A		L-2-hydroxyglutaric aciduria	Likely benign (Sep 19, 2022)

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