IVD

isovaleryl-CoA dehydrogenase, the group of Acyl-CoA dehydrogenase family

Basic information

Region (hg38): 15:40405484-40435947

Links

ENSG00000128928 ∙ NCBI:3712 ∙ OMIM:607036 ∙ HGNC:6186 ∙ Uniprot:P26440 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isovaleric acidemia (Definitive), mode of inheritance: AR
• isovaleric acidemia (Definitive), mode of inheritance: AR
• isovaleric acidemia (Strong), mode of inheritance: AR
• isovaleric acidemia (Supportive), mode of inheritance: AR
• isovaleric acidemia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Isovaleric acidemia	AR	Biochemical	Medical/dietary treatment (eg, with l-carnitine, glycine, and leucine restricted/low protein diet) can be effective; Specific measures can be taken to prevent severe sequelae of acute metabolic decompensation	Biochemical; Cardiovascular; Neurologic	5229850; 4378266; 4166104; 692626; 6630517; 3863140; 3139936; 3137519; 2063866; 15486829; 20142522; 20301313; 20662350; 20807522; 21207059; 21335445; 22004070; 22350545; 22960500; 23063737

ClinVar

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

• Isovaleryl-CoA dehydrogenase deficiency (562 variants)
• not provided (83 variants)
• not specified (44 variants)
• Inborn genetic diseases (18 variants)
• IVD-related condition (5 variants)
• Isovaleric acidemia, type I (1 variants)
• Isovaleric acidemia, type III (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IVD 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			3	153	2	158
missense	3	34	101	2	1	141
nonsense	7	12				19
start loss		1	1			2
frameshift	17	23				40
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	23				26
splice region		1	6	33	2	42
non coding		1	49	69	39	158
Total	30	94	155	224	42

Highest pathogenic variant AF is 0.000729

Variants in IVD

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

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

Position	Type	Phenotype	Significance	ClinVar
15-40405504-C-G		Isovaleryl-CoA dehydrogenase deficiency	Uncertain significance (Jun 14, 2016)
15-40405541-T-G			Likely benign (Jan 24, 2020)
15-40405582-G-C		Isovaleryl-CoA dehydrogenase deficiency	Uncertain significance (Jun 14, 2016)
15-40405740-C-G		Isovaleryl-CoA dehydrogenase deficiency	Likely benign (Jun 14, 2016)
15-40405780-G-A		Isovaleryl-CoA dehydrogenase deficiency • not specified	Benign/Likely benign (Jun 14, 2016)
15-40405792-C-T		not specified	Likely benign (Mar 28, 2017)
15-40405819-A-T		Isovaleryl-CoA dehydrogenase deficiency	Conflicting classifications of pathogenicity (Aug 17, 2022)
15-40405820-T-C		Isovaleryl-CoA dehydrogenase deficiency	Conflicting classifications of pathogenicity (Oct 05, 2022)
15-40405820-T-G		Isovaleryl-CoA dehydrogenase deficiency	Uncertain significance (Sep 05, 2017)
15-40405824-A-G		Isovaleryl-CoA dehydrogenase deficiency	Likely benign (Nov 14, 2020)
15-40405828-A-C			Likely pathogenic (Sep 29, 2016)
15-40405829-T-C		Isovaleryl-CoA dehydrogenase deficiency	Uncertain significance (Nov 08, 2022)
15-40405832-C-T		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
15-40405833-G-T		Isovaleryl-CoA dehydrogenase deficiency	Likely benign (Jan 24, 2022)
15-40405836-T-C		Isovaleryl-CoA dehydrogenase deficiency	Likely benign (Sep 26, 2023)
15-40405838-C-T		not specified • Isovaleryl-CoA dehydrogenase deficiency • IVD-related disorder	Likely benign (Jan 31, 2024)
15-40405839-G-C		Isovaleryl-CoA dehydrogenase deficiency	Likely benign (Mar 21, 2023)
15-40405842-T-C		Isovaleryl-CoA dehydrogenase deficiency	Likely benign (May 13, 2021)
15-40405844-G-A		Isovaleryl-CoA dehydrogenase deficiency	Uncertain significance (Sep 07, 2022)
15-40405849-C-T		Isovaleryl-CoA dehydrogenase deficiency	Likely benign (Nov 24, 2021)
15-40405852-G-T		Isovaleryl-CoA dehydrogenase deficiency	Uncertain significance (Feb 04, 2022)
15-40405854-G-T		Isovaleryl-CoA dehydrogenase deficiency	Likely benign (Nov 08, 2023)
15-40405860-T-C		Isovaleryl-CoA dehydrogenase deficiency	Likely benign (Oct 14, 2020)
15-40405861-G-A		Isovaleryl-CoA dehydrogenase deficiency • Inborn genetic diseases	Uncertain significance (Mar 10, 2022)
15-40405863-G-A		Isovaleryl-CoA dehydrogenase deficiency	Likely benign (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IVD	protein_coding	protein_coding	ENST00000487418	12	30461

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.53e-14	0.0260	125683	0	65	125748	0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.349	231	246	0.937	0.0000148	2785
Missense in Polyphen		82	107.9	0.75998		1199
Synonymous	0.222	99	102	0.972	0.00000639	850
Loss of Function	0.243	22	23.3	0.946	0.00000125	255

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000506	0.000506
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.0000933	0.0000924
European (Non-Finnish)	0.000308	0.000308
Middle Eastern	0.000217	0.000217
South Asian	0.000359	0.000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Isovaleric acidemia (IVA) [MIM:243500]: A metabolic disorder characterized by retarded psychomotor development, a peculiar odor resembling sweaty feet, an aversion to dietary protein, and pernicious vomiting, leading to acidosis and coma. The acute neonatal form leads to massive metabolic acidosis from the first days of life and rapid death. {ECO:0000269|PubMed:2063866, ECO:0000269|PubMed:22004070, ECO:0000269|PubMed:22350545, ECO:0000269|PubMed:23587913, ECO:0000269|PubMed:28535199, ECO:0000269|PubMed:9665741}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Valine, leucine and isoleucine degradation - Homo sapiens (human);Valproic Acid Pathway, Pharmacokinetics;3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Maple Syrup Urine Disease;Valproic Acid Metabolism Pathway;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Isovaleric acidemia;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Methylmalonic Aciduria;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Beta-Ketothiolase Deficiency;Valproic acid pathway;Branched-chain amino acid catabolism;Metabolism of amino acids and derivatives;leucine degradation;Metabolism;Valine, leucine and isoleucine degradation;Valine Leucine Isoleucine degradation (Consensus)

Recessive Scores

• pRec: 0.462

Intolerance Scores

• loftool: 0.154
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.34

Haploinsufficiency Scores

• pHI: 0.100
• hipred: N
• hipred_score: 0.393
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.555

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ivd
• Phenotype: homeostasis/metabolism phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: leucine catabolic process;branched-chain amino acid catabolic process;fatty acid beta-oxidation using acyl-CoA dehydrogenase
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: protein binding;isovaleryl-CoA dehydrogenase activity;flavin adenine dinucleotide binding