ACAD8

Summary

ACAD8 (acyl-CoA dehydrogenase family member 8, HGNC:87) is a protein-coding gene on chromosome 11q25, encoding Isobutyryl-CoA dehydrogenase, mitochondrial (Q9UKU7). Isobutyryl-CoA dehydrogenase which catalyzes the conversion of 2-methylpropanoyl-CoA to (2E)-2-methylpropenoyl-CoA in the valine catabolic pathway.

This gene encodes a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. The encoded protein is a mitochondrial enzyme that functions in catabolism of the branched-chain amino acid valine. Defects in this gene are the cause of isobutyryl-CoA dehydrogenase deficiency.

Source: NCBI Gene 27034 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isobutyryl-CoA dehydrogenase deficiency (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 382 total — 70 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 13
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_014384

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:87
Approved symbol	ACAD8
Name	acyl-CoA dehydrogenase family member 8
Location	11q25
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000151498
Ensembl biotype	protein_coding
OMIM	604773
Entrez	27034

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 15 protein_coding, 11 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000281182, ENST00000374752, ENST00000524426, ENST00000524502, ENST00000524547, ENST00000524739, ENST00000525961, ENST00000526026, ENST00000527082, ENST00000527665, ENST00000527713, ENST00000528325, ENST00000530533, ENST00000531338, ENST00000533387, ENST00000534240, ENST00000534433, ENST00000869564, ENST00000869565, ENST00000869566, ENST00000869567, ENST00000869568, ENST00000869569, ENST00000869570, ENST00000918779, ENST00000952155, ENST00000952156, ENST00000952157, ENST00000952158, ENST00000952159

RefSeq mRNA: 1 — MANE Select: NM_014384 NM_014384

CCDS: CCDS8498

Canonical transcript exons

ENST00000281182 — 11 exons

Exon	Start	End
ENSE00000999980	134253568	134253709
ENSE00002140309	134264908	134265855
ENSE00003460149	134257088	134257257
ENSE00003517380	134259008	134259084
ENSE00003528004	134261275	134261372
ENSE00003532466	134259608	134259745
ENSE00003545985	134261044	134261179
ENSE00003557606	134258515	134258624
ENSE00003587179	134262520	134262622
ENSE00003651876	134256548	134256648
ENSE00003658535	134261738	134261890

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 95.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2795 / max 193.3725, expressed in 1814 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117701	17.2795	1814

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	95.20	gold quality
left lobe of thyroid gland	UBERON:0001120	94.56	gold quality
cerebellar hemisphere	UBERON:0002245	94.46	gold quality
body of pancreas	UBERON:0001150	94.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.34	gold quality
cerebellar cortex	UBERON:0002129	94.23	gold quality
thyroid gland	UBERON:0002046	93.23	gold quality
apex of heart	UBERON:0002098	93.05	gold quality
cerebellum	UBERON:0002037	92.69	gold quality
skin of leg	UBERON:0001511	92.60	gold quality
skin of abdomen	UBERON:0001416	92.47	gold quality
right frontal lobe	UBERON:0002810	92.25	gold quality
metanephros cortex	UBERON:0010533	92.14	gold quality
right lobe of liver	UBERON:0001114	91.99	gold quality
gastrocnemius	UBERON:0001388	91.91	gold quality
heart left ventricle	UBERON:0002084	91.69	gold quality
right adrenal gland cortex	UBERON:0035827	91.55	gold quality
right adrenal gland	UBERON:0001233	91.52	gold quality
muscle of leg	UBERON:0001383	91.46	gold quality
minor salivary gland	UBERON:0001830	91.38	gold quality
cardiac ventricle	UBERON:0002082	91.28	gold quality
left adrenal gland	UBERON:0001234	91.25	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.05	gold quality
upper leg skin	UBERON:0004262	91.04	gold quality
left adrenal gland cortex	UBERON:0035825	91.00	gold quality
body of uterus	UBERON:0009853	90.98	gold quality
body of stomach	UBERON:0001161	90.95	gold quality
granulocyte	CL:0000094	90.84	gold quality
zone of skin	UBERON:0000014	90.70	gold quality
right atrium auricular region	UBERON:0006631	90.55	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.45
E-MTAB-7606	no	136.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting ACAD8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-129-1-3P	98.86	68.41	779

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 2)

• first enzymatic and molecular confirmation of a deficiency of this enzyme in a patient (PMID:12359132)
• we discovered a novel c.1156_1158delCAG mutation in ACAD8 in patients with isobutyryl-CoA dehydrogenase deficiency , and investigated the mutation spectrum of ACAD8. (PMID:24635911)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	acad8	ENSDARG00000042658
mus_musculus	Acad8	ENSMUSG00000031969
rattus_norvegicus	Acad8	ENSRNOG00000048164
caenorhabditis_elegans		WBGENE00017874

Paralogs (14): ACADVL (ENSG00000072778), ACOX3 (ENSG00000087008), GCDH (ENSG00000105607), ACAD10 (ENSG00000111271), ACADL (ENSG00000115361), ACADM (ENSG00000117054), ACADS (ENSG00000122971), IVD (ENSG00000128928), ACOXL (ENSG00000153093), ACOX1 (ENSG00000161533), ACOX2 (ENSG00000168306), ACAD9 (ENSG00000177646), ACADSB (ENSG00000196177), ACAD11 (ENSG00000240303)

Protein

Protein identifiers

Isobutyryl-CoA dehydrogenase, mitochondrial — Q9UKU7 (reviewed: Q9UKU7)

Alternative names: Activator-recruited cofactor 42 kDa component, Acyl-CoA dehydrogenase family member 8

All UniProt accessions (3): Q9UKU7, E9PKP9, E9PLS3

UniProt curated annotations — full annotation on UniProt →

Function. Isobutyryl-CoA dehydrogenase which catalyzes the conversion of 2-methylpropanoyl-CoA to (2E)-2-methylpropenoyl-CoA in the valine catabolic pathway. To a lesser extent, also able to catalyze the oxidation of (2S)-2-methylbutanoyl-CoA.

Subunit / interactions. Homotetramer, formed by a dimer of dimers. May be part of the large multiprotein complex ARC/DRIP.

Subcellular location. Mitochondrion.

Tissue specificity. Detected at comparable levels in heart, lung, brain, skeletal muscle, pancreas and placenta. Weakly expressed in liver and kidney.

Disease relevance. Isobutyryl-CoA dehydrogenase deficiency (IBDD) [MIM:611283] An autosomal recessive metabolic disorder characterized by plasma carnitine deficiency and elevated C4-acylcarnitine. Patients manifest variable clinical features including failure to thrive, seizures, anemia, muscular hypotonia and developmental delay. Some patients may be asymptomatic. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Amino-acid degradation; L-valine degradation.

Similarity. Belongs to the acyl-CoA dehydrogenase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UKU7-1	1	yes
Q9UKU7-2	2
Q9UKU7-3	3

RefSeq proteins (1): NP_055199* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006089	Acyl-CoA_DH_CS	Conserved_site
IPR006091	AcylCoA_DH/ox_M	Domain
IPR009075	AcylCo_DH/oxidase_C	Domain
IPR009100	AcylCoA_DH/oxidase_NM_dom_sf	Homologous_superfamily
IPR013786	AcylCoA_DH/ox_N	Domain
IPR034178	IBD	Family
IPR036250	AcylCo_DH-like_C	Homologous_superfamily
IPR037069	AcylCoA_DH/ox_N_sf	Homologous_superfamily
IPR046373	Acyl-CoA_Oxase/DH_mid-dom_sf	Homologous_superfamily
IPR052547	Mito_Isobutyryl-CoADH	Family

Pfam: PF00441, PF02770, PF02771

Catalyzed reactions (Rhea), 3 shown:

• propanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = acryloyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:31287)
• 2-methylpropanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = 2-methylpropenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:44180)
• (2S)-2-methylbutanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:48256)

UniProt features (62 total): helix 17, strand 11, binding site 9, sequence variant 9, modified residue 4, splice variant 4, turn 4, transit peptide 1, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1RX0	X-RAY DIFFRACTION	1.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKU7-F1	94.19	0.93

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 398 (proton acceptor)

Ligand- & substrate-binding residues (9): 400–402 (in other chain); 410; 158–167 (in other chain); 167; 191–193 (in other chain); 274–277; 302; 312–313; 371–375

Post-translational modifications (4): 50, 50, 213, 231

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-70895	Branched-chain amino acid catabolism
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-1430728	Metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 156 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, MARTINEZ_RB1_TARGETS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_AMINO_ACID_CATABOLIC_PROCESS, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, DANG_BOUND_BY_MYC

GO Biological Process (3): L-valine catabolic process (GO:0006574), lipid metabolic process (GO:0006629), branched-chain amino acid catabolic process (GO:0009083)

GO Molecular Function (6): short-chain 2-methyl fatty acyl-CoA dehydrogenase activity (GO:0003853), acyl-CoA dehydrogenase activity (GO:0003995), flavin adenine dinucleotide binding (GO:0050660), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors (GO:0016627)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism of proteins	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
branched-chain amino acid catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
primary metabolic process	1
amino acid catabolic process	1
branched-chain amino acid metabolic process	1
carboxylic acid catabolic process	1
short-chain fatty acyl-CoA dehydrogenase activity	1
oxidoreductase activity, acting on the CH-CH group of donors, with a flavin as acceptor	1
nucleotide binding	1
anion binding	1
binding	1
catalytic activity	1
oxidoreductase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

2274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACAD8	ACAA2	P42765	564
ACAD8	HMGCL	P35914	542
ACAD8	HIBADH	P31937	519
ACAD8	ETFDH	Q16134	516
ACAD8	ITGB3BP	Q13352	508
ACAD8	HIBCH	Q6NVY1	491
ACAD8	ACOT8	O14734	483
ACAD8	DMGDH	Q9UI17	482
ACAD8	ETFA	P13804	478
ACAD8	BCKDHA	P12694	475
ACAD8	BCKDHB	P21953	475
ACAD8	ALDH6A1	Q02252	471
ACAD8	MCCC1	Q96RQ3	451
ACAD8	ACAD10	Q6JQN1	441
ACAD8	HADHB	P55084	437

IntAct

35 interactions, top by confidence:

A	B	Type	Score
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
VPS37D	CRTAP	psi-mi:“MI:0914”(association)	0.530
FAM161B	KLHL15	psi-mi:“MI:0914”(association)	0.530
CD79A	METTL15	psi-mi:“MI:0914”(association)	0.530
CD79A	ODR4	psi-mi:“MI:0914”(association)	0.530
VSTM2A	ACAD8	psi-mi:“MI:0915”(physical association)	0.500
VSTM2A	ACAD8	psi-mi:“MI:0915”(physical association)	0.400
Nek2	NEK2	psi-mi:“MI:0915”(physical association)	0.400
GMIP	ACAD8	psi-mi:“MI:0915”(physical association)	0.400
OLIG1	ACAD8	psi-mi:“MI:0915”(physical association)	0.400
ACAD8	PCNA	psi-mi:“MI:0915”(physical association)	0.370
TSG101	ACAD8	psi-mi:“MI:0915”(physical association)	0.370
CKAP5	TACC3	psi-mi:“MI:0914”(association)	0.350
DLG3	WDR91	psi-mi:“MI:0914”(association)	0.350
IPO8	BIN1	psi-mi:“MI:0914”(association)	0.350
LDHD	METTL8	psi-mi:“MI:0914”(association)	0.350
Tgfbr1	HSPA8	psi-mi:“MI:0914”(association)	0.350
SRGAP3	CCDC85C	psi-mi:“MI:0914”(association)	0.350
FCGR1A	PCDH17	psi-mi:“MI:0914”(association)	0.350
DUSP14	ACOX1	psi-mi:“MI:0914”(association)	0.350
POLM	CTU2	psi-mi:“MI:0914”(association)	0.350
VPS37D	RPSA2	psi-mi:“MI:0914”(association)	0.350
VSTM2A	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): ACAD8 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), ACADSB (Co-fractionation), ACAD8 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), ACAD8 (Reconstituted Complex), ACAD8 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS)

ESM2 similar proteins: B1WC61, B3DMA2, O32176, O64894, O65201, P07872, P12007, P15650, P26440, P28330, P45953, P45954, P48818, P49748, P50544, P51174, P70584, P79273, P79274, Q0NXR6, Q15067, Q3SZI8, Q3SZP5, Q47146, Q54IM8, Q54RR5, Q5EAD4, Q5R778, Q5RBD5, Q5RC19, Q5RF40, Q5ZHT1, Q60HI0, Q64428, Q6JQN1, Q709F0, Q80XL6, Q8HXY7, Q8JZN5, Q8X7R2

Diamond homologs: A5A6I0, A8WP91, A8XNF0, B1WC61, B9U6P5, C3UVB0, D3JV03, F8GVD3, G3KIM8, H6LGM6, I6Y3V5, J7TF92, K4L7X3, O32176, O34421, O54143, P08503, P0A9U8, P0A9U9, P0A9V0, P11310, P12007, P15650, P15651, P16219, P26440, P28330, P41367, P45857, P45867, P45952, P45953, P45954, P46703, P48818, P49748, P50544, P51174, P52042, P63428

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

382 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	70
Likely pathogenic	19
Uncertain significance	150
Likely benign	58
Benign	41

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069419	NM_014384.3(ACAD8):c.1092+1G>C	Pathogenic
1201254	NM_014384.3(ACAD8):c.915dup (p.Gly306fs)	Pathogenic
144517	GRCh38/hg38 11q25(chr11:132936725-134998513)x1	Pathogenic
1452755	NM_014384.3(ACAD8):c.286G>A (p.Gly96Ser)	Pathogenic
1452933	NM_014384.3(ACAD8):c.1092+1G>A	Pathogenic
145308	GRCh38/hg38 11q24.1-25(chr11:123799938-134998526)x1	Pathogenic
145337	GRCh38/hg38 11q24.2-25(chr11:124205225-134998526)x1	Pathogenic
1459900	NC_000011.9:g.(?133778964)(134134854_?)del	Pathogenic
147420	GRCh38/hg38 11q24.2-25(chr11:125241472-134998513)x1	Pathogenic
148509	GRCh38/hg38 11q25(chr11:131212028-135075271)x1	Pathogenic
148952	GRCh38/hg38 11q24.1-25(chr11:121780459-135075271)x1	Pathogenic
149105	GRCh38/hg38 11q24.2-25(chr11:126046358-135075271)x1	Pathogenic
149328	GRCh38/hg38 11q23.3-25(chr11:120515759-135075271)x1	Pathogenic
149547	GRCh38/hg38 11q24.1-25(chr11:123963074-135075271)x1	Pathogenic
149702	GRCh38/hg38 11q24.2-25(chr11:124940059-135075271)x1	Pathogenic
150032	GRCh38/hg38 11q23.3-25(chr11:119424297-135075271)x1	Pathogenic
150232	GRCh38/hg38 11q24.2-25(chr11:126199589-135075271)x1	Pathogenic
151164	GRCh38/hg38 11q24.2-25(chr11:124315025-134818116)x1	Pathogenic
154045	GRCh38/hg38 11q24.1-25(chr11:121806547-135068576)x1	Pathogenic
154559	GRCh38/hg38 11q24.3-25(chr11:130706504-135075271)x1	Pathogenic
155688	GRCh38/hg38 11q24.3-25(chr11:127915964-135068576)x1	Pathogenic
1711169	GRCh37/hg19 11q25(chr11:130880039-134938470)x3	Pathogenic
1954125	NM_014384.3(ACAD8):c.589G>T (p.Glu197Ter)	Pathogenic
2074051	NM_014384.3(ACAD8):c.616C>T (p.Arg206Ter)	Pathogenic
2505490	GRCh37/hg19 11q25(chr11:131952484-134938470)x1	Pathogenic
253521	GRCh37/hg19 11q23.3-25(chr11:120615374-134868407)x1	Pathogenic
253565	GRCh37/hg19 11q24.2-25(chr11:126631558-134868407)x1	Pathogenic
253601	GRCh37/hg19 11q23.3-25(chr11:119807473-134868407)x1	Pathogenic
2716443	NM_014384.3(ACAD8):c.886C>T (p.Arg296Ter)	Pathogenic
2954661	NM_014384.3(ACAD8):c.473A>C (p.Tyr158Ser)	Pathogenic

SpliceAI

2429 predictions. Top by Δscore:

Variant	Effect	Δscore
11:134257258:G:GG	donor_gain	1.0000
11:134258994:T:TA	acceptor_gain	1.0000
11:134261369:CCAG:C	donor_loss	1.0000
11:134261370:CAG:C	donor_loss	1.0000
11:134261371:AGGT:A	donor_loss	1.0000
11:134261372:GG:G	donor_loss	1.0000
11:134261373:GT:G	donor_loss	1.0000
11:134261374:T:G	donor_loss	1.0000
11:134261736:A:AG	acceptor_gain	1.0000
11:134261737:G:GG	acceptor_gain	1.0000
11:134261888:GCC:G	donor_gain	1.0000
11:134261888:GCCGT:G	donor_loss	1.0000
11:134261889:CC:C	donor_gain	1.0000
11:134261889:CCGT:C	donor_loss	1.0000
11:134261890:CG:C	donor_loss	1.0000
11:134261891:G:GG	donor_gain	1.0000
11:134261892:T:G	donor_loss	1.0000
11:134262515:TGCA:T	acceptor_loss	1.0000
11:134262516:GCAG:G	acceptor_loss	1.0000
11:134262518:A:AG	acceptor_gain	1.0000
11:134262518:AGA:A	acceptor_loss	1.0000
11:134262519:G:GG	acceptor_gain	1.0000
11:134262519:GA:G	acceptor_gain	1.0000
11:134262519:GAT:G	acceptor_gain	1.0000
11:134262519:GATC:G	acceptor_gain	1.0000
11:134262519:GATCT:G	acceptor_gain	1.0000
11:134262582:GCA:G	donor_gain	1.0000
11:134262585:G:GG	donor_gain	1.0000
11:134262619:GAAG:G	donor_gain	1.0000
11:134262621:AGGT:A	donor_loss	1.0000

AlphaMissense

2723 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:134257247:A:C	S124R	0.998
11:134257249:C:A	S124R	0.998
11:134257249:C:G	S124R	0.998
11:134258611:C:G	C159W	0.998
11:134259084:G:C	K189N	0.997
11:134259084:G:T	K189N	0.997
11:134259611:T:C	F191L	0.997
11:134259613:C:A	F191L	0.997
11:134259613:C:G	F191L	0.997
11:134259617:A:C	S193R	0.997
11:134259619:T:A	S193R	0.997
11:134259619:T:G	S193R	0.997
11:134261050:T:A	W238R	0.997
11:134261050:T:C	W238R	0.997
11:134257229:A:C	S118R	0.995
11:134257231:C:A	S118R	0.995
11:134257231:C:G	S118R	0.995
11:134258609:T:C	C159R	0.994
11:134258610:G:A	C159Y	0.994
11:134261144:C:A	A269D	0.994
11:134261346:T:C	F305L	0.994
11:134261348:T:A	F305L	0.994
11:134261348:T:G	F305L	0.994
11:134262548:G:A	G374E	0.994
11:134256593:C:A	A52D	0.993
11:134261048:G:A	G237E	0.993
11:134261289:G:T	G286W	0.993
11:134261296:C:A	A288D	0.993
11:134262557:G:A	G377D	0.993
11:134256605:C:A	A56D	0.992

dbSNP variants (sampled 300 via entrez): RS1000039276 (11:134265645 A>G), RS1000054002 (11:134254346 G>A), RS1000235444 (11:134253980 C>T), RS1000860241 (11:134264981 T>C), RS1001297741 (11:134264539 C>A), RS1001390049 (11:134259224 C>G,T), RS1001396121 (11:134265232 T>C), RS1001433080 (11:134264907 G>A), RS1001492207 (11:134253893 G>A), RS1001876575 (11:134255127 T>A,C), RS1002006560 (11:134255117 A>G), RS1002498162 (11:134253100 C>A,T), RS1002741185 (11:134252716 G>A,C), RS1003508598 (11:134257781 A>G), RS1003524271 (11:134263503 C>G,T)

Disease associations

OMIM: gene MIM:604773 | disease phenotypes: MIM:611283, MIM:147791

GenCC curated gene-disease

Disease	Classification	Inheritance
isobutyryl-CoA dehydrogenase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
isobutyryl-CoA dehydrogenase deficiency	Definitive	AR

Mondo (2): isobutyryl-CoA dehydrogenase deficiency (MONDO:0012648), Jacobsen syndrome (MONDO:0007838)

Orphanet (3): Isobutyryl-CoA dehydrogenase deficiency (Orphanet:79159), Syndromic anorectal malformation (Orphanet:117573), Jacobsen syndrome (Orphanet:2308)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000750	Delayed speech and language development
HP:0001252	Hypotonia
HP:0001642	Pulmonic stenosis
HP:0001644	Dilated cardiomyopathy
HP:0001903	Anemia
HP:0001944	Dehydration
HP:0002013	Vomiting
HP:0003215	Dicarboxylic aciduria
HP:0003234	Decreased circulating carnitine concentration
HP:0011342	Mild global developmental delay
HP:0012734	Ketotic hypoglycemia
HP:0045045	Elevated circulating acylcarnitine concentration

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_202	Obesity-related traits	7.000000e-06
GCST001762_595	Obesity-related traits	7.000000e-06
GCST012020_444	Serum metabolite levels	1.000000e-23

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005134	amino acid measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535541	Isobutyryl-CoA dehydrogenase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, decreases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
lead acetate	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Dexamethasone	decreases expression, affects cotreatment	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	decreases expression, affects cotreatment	1
Isotretinoin	decreases expression	1
Cyclosporine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_IN34	GM17476	Finite cell line	Female

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes