ACAD9

acyl-CoA dehydrogenase family member 9, the group of Mitochondrial complex I assembly complex|Acyl-CoA dehydrogenase family

Basic information

Region (hg38): 3:128879595-128924003

Links

ENSG00000177646 ∙ NCBI:28976 ∙ OMIM:611103 ∙ HGNC:21497 ∙ Uniprot:Q9H845 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acyl-CoA dehydrogenase 9 deficiency (Definitive), mode of inheritance: AR
• acyl-CoA dehydrogenase 9 deficiency (Strong), mode of inheritance: AR
• acyl-CoA dehydrogenase 9 deficiency (Strong), mode of inheritance: AR
• acyl-CoA dehydrogenase 9 deficiency (Supportive), mode of inheritance: AR
• acyl-CoA dehydrogenase 9 deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 20	AR	Biochemical	Individuals may present early in life with findings including neurologic abnormalities, cardiomyopathy, and lactic acidosis, and early institution of medical treatment (eg, with riboflavin) has been reported as leading to marked decreases in morbidity/mortality	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	17564966; 21057504; 20929961; 21057504; 22499348; 25721401

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACAD9 gene.

• not provided (738 variants)
• Acyl-CoA dehydrogenase 9 deficiency (201 variants)
• not specified (43 variants)
• Inborn genetic diseases (31 variants)
• Mitochondrial complex I deficiency (13 variants)
• ACAD9-related condition (3 variants)
• - (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACAD9 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				212	5	217
missense	2	19	151	14	1	187
nonsense	9	10				19
start loss	3					3
frameshift	24	27				51
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)	2	39				41
splice region			12	53	1	66
non coding			14	126	64	204
Total	40	96	169	352	70

Highest pathogenic variant AF is 0.0000263

Variants in ACAD9

This is a list of pathogenic ClinVar variants found in the ACAD9 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-128879601-G-T		Acyl-CoA dehydrogenase 9 deficiency	Uncertain significance (Jun 14, 2016)
3-128879626-CGT-C		Acyl-CoA dehydrogenase 9 deficiency	Benign (Jul 14, 2021)
3-128879626-C-CGT		Acyl-CoA dehydrogenase 9 deficiency	Uncertain significance (Jun 14, 2016)
3-128879647-C-CTAAG		Acyl-CoA dehydrogenase 9 deficiency • not specified	Conflicting classifications of pathogenicity (Dec 18, 2023)
3-128879681-C-T		not specified	Likely benign (Apr 18, 2017)
3-128879682-A-T		ACAD9-related disorder	Likely benign (Jan 07, 2020)
3-128879692-A-G			Pathogenic (Dec 17, 2023)
3-128879692-A-T			Pathogenic (Jan 09, 2024)
3-128879693-T-G		-	no classification for the single variant (-)
3-128879694-G-A			Pathogenic (Mar 20, 2021)
3-128879695-A-G			Uncertain significance (Jun 13, 2022)
3-128879696-G-A			Uncertain significance (Jan 28, 2022)
3-128879696-G-T			Uncertain significance (Oct 09, 2023)
3-128879695-A-AGCGGCTGCGGGCTCTTCCTGCGCACC		Acyl-CoA dehydrogenase 9 deficiency	Likely pathogenic (Jun 29, 2022)
3-128879696-GCGGCTGCGGGCTCTTCCTGCGCACCA-G		Acyl-CoA dehydrogenase 9 deficiency	Pathogenic/Likely pathogenic (Aug 30, 2023)
3-128879697-C-G		Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
3-128879697-C-T			Likely benign (Aug 20, 2023)
3-128879700-C-T			Likely benign (Jan 18, 2023)
3-128879702-G-T		not specified	Likely benign (Dec 03, 2012)
3-128879703-C-T			Likely benign (Jan 05, 2024)
3-128879706-G-T			Likely benign (Jan 24, 2024)
3-128879708-T-C			Uncertain significance (Feb 22, 2022)
3-128879709-C-G			Likely benign (Mar 18, 2022)
3-128879709-C-T			Likely benign (Jul 25, 2022)
3-128879713-C-T			Likely benign (Feb 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACAD9	protein_coding	protein_coding	ENST00000308982	18	36472

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.53e-8	0.990	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.179	367	357	1.03	0.0000224	4054
Missense in Polyphen		118	131.93	0.89441		1430
Synonymous	-0.170	147	144	1.02	0.00000954	1240
Loss of Function	2.37	17	31.3	0.543	0.00000155	379

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000832	0.000829
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000257	0.000255
Middle Eastern	0.000109	0.000109
South Asian	0.000262	0.000261
Other	0.000656	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for mitochondrial complex I assembly (PubMed:20816094, PubMed:24158852). Has a dehydrogenase activity on palmitoyl-CoA (C16:0) and stearoyl-CoA (C18:0). It is three times more active on palmitoyl-CoA than on stearoyl-CoA. However, it does not play a primary role in long-chain fatty acid oxidation in vivo (PubMed:20816094, PubMed:24158852). Has little activity on octanoyl-CoA (C8:0), butyryl-CoA (C4:0) or isovaleryl-CoA (5:0). {ECO:0000269|PubMed:20816094, ECO:0000269|PubMed:24158852}.
• Pathway: Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Complex I biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.223

Intolerance Scores

• loftool: 0.168
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.36

Haploinsufficiency Scores

• pHI: 0.104
• hipred: N
• hipred_score: 0.492
• ghis: 0.554

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acad9

Gene ontology

• Biological process: long-chain fatty acid metabolic process;mitochondrial respiratory chain complex I assembly;medium-chain fatty acid metabolic process;oxidation-reduction process
• Cellular component: nucleus;mitochondrion;mitochondrial inner membrane;dendrite;mitochondrial membrane
• Molecular function: fatty-acyl-CoA binding;long-chain-acyl-CoA dehydrogenase activity;protein binding;very-long-chain-acyl-CoA dehydrogenase activity;flavin adenine dinucleotide binding;medium-chain-acyl-CoA dehydrogenase activity