IVD

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

Basic information

Region (hg38): 15:40405485-40435947

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 (626 variants)
not_provided (74 variants)
not_specified (65 variants)
Inborn_genetic_diseases (46 variants)
IVD-related_disorder (17 variants)
Isovaleric_acidemia,_type_I (2 variants)
Isovaleric_acidemia,_type_III (1 variants)
Intellectual_disability (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. These statistics are base on transcript: NM_000002225.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		3 clinvar	201 clinvar	1 clinvar	206
missense	5 clinvar	62 clinvar	139 clinvar	4 clinvar	1 clinvar	211
nonsense	12 clinvar	11 clinvar				23
start loss		2	1			3
frameshift	26 clinvar	27 clinvar				53
splice donor/acceptor (+/-2bp)	9 clinvar	27 clinvar				36
Total	53	129	143	205	2

Highest pathogenic variant AF is 0.0009014

Loading clinvar variants...

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