AUH

AU RNA binding methylglutaconyl-CoA hydratase

Basic information

Region (hg38): 9:91213814-91361918

Links

ENSG00000148090 ∙ NCBI:549 ∙ OMIM:600529 ∙ HGNC:890 ∙ Uniprot:Q13825 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3-methylglutaconic aciduria type 1 (Definitive), mode of inheritance: AR
• 3-methylglutaconic aciduria type 1 (Strong), mode of inheritance: AR
• 3-methylglutaconic aciduria type 1 (Supportive), mode of inheritance: AR
• 3-methylglutaconic aciduria type 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
3-methylglutaconic aciduria, type I	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic; Ophthalmologic	720359; 3082934; 1710267; 1375542; 9762598; 10070612; 12434311; 15033206; 16354225; 17130438; 20855850; 21840233; 23296368
Dietary measures (leucine restriction) have been suggested

ClinVar

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

• 3-methylglutaconic aciduria type 1 (171 variants)
• not provided (54 variants)
• not specified (21 variants)
• Inborn genetic diseases (17 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AUH 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			2	24	1	27
missense	1	4	81	2	1	89
nonsense	2	1	1			4
start loss			1			1
frameshift	4	1				5
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	3				6
splice region			6	7	3	16
non coding			8	25	13	46
Total	10	9	95	51	15

Highest pathogenic variant AF is 0.000112

Variants in AUH

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

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

Position	Type	Phenotype	Significance	ClinVar
9-91213916-G-A		3-methylglutaconic aciduria type 1	Uncertain significance (Jan 13, 2018)
9-91214085-GTAAA-G		3-methylglutaconic aciduria type 1	Uncertain significance (Jun 14, 2016)
9-91214111-C-T		3-methylglutaconic aciduria type 1	Uncertain significance (Jan 12, 2018)
9-91214128-ACT-A		3-methylglutaconic aciduria type 1	Uncertain significance (Jun 14, 2016)
9-91214148-T-C		3-methylglutaconic aciduria type 1	Benign (Jan 13, 2018)
9-91214173-C-T		3-methylglutaconic aciduria type 1	Uncertain significance (Jan 13, 2018)
9-91214241-T-C		3-methylglutaconic aciduria type 1	Benign (Jun 16, 2018)
9-91214288-C-T		3-methylglutaconic aciduria type 1	Uncertain significance (Jan 13, 2018)
9-91214319-C-T		3-methylglutaconic aciduria type 1	Uncertain significance (Jan 13, 2018)
9-91214364-C-T		3-methylglutaconic aciduria type 1 • Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
9-91214365-G-A		3-methylglutaconic aciduria type 1 • Inborn genetic diseases	Uncertain significance (Sep 27, 2021)
9-91214370-G-A		3-methylglutaconic aciduria type 1	Uncertain significance (Oct 03, 2023)
9-91214371-G-T		3-methylglutaconic aciduria type 1	Uncertain significance (Aug 04, 2023)
9-91214372-C-T		3-methylglutaconic aciduria type 1	Likely benign (Oct 13, 2023)
9-91214377-T-A		3-methylglutaconic aciduria type 1	Uncertain significance (Dec 26, 2017)
9-91214388-G-C		3-methylglutaconic aciduria type 1	Uncertain significance (Jul 02, 2022)
9-91214395-G-C		3-methylglutaconic aciduria type 1 • Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
9-91214417-T-A		3-methylglutaconic aciduria type 1 • not specified	Conflicting classifications of pathogenicity (Aug 16, 2022)
9-91214427-T-C		3-methylglutaconic aciduria type 1 • AUH-related disorder	Likely pathogenic (Dec 11, 2023)
9-91214430-GA-G		3-methylglutaconic aciduria type 1	Benign (Jul 29, 2021)
9-91214431-A-G		3-methylglutaconic aciduria type 1	Benign (Dec 21, 2023)
9-91214441-T-C		3-methylglutaconic aciduria type 1	Likely benign (Jun 09, 2022)
9-91214646-GTTA-G			Benign (Jul 15, 2018)
9-91215824-T-C			Likely benign (Dec 25, 2019)
9-91216054-C-CA		3-methylglutaconic aciduria type 1	Uncertain significance (Apr 09, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AUH	protein_coding	protein_coding	ENST00000375731	10	148099

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000802	0.924	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.342	169	182	0.929	0.00000952	2129
Missense in Polyphen		62	83.615	0.7415		927
Synonymous	0.196	67	69.1	0.970	0.00000390	706
Loss of Function	1.68	11	18.9	0.582	0.00000107	217

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000231	0.000231
Ashkenazi Jewish	0.000104	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00102	0.00102
European (Non-Finnish)	0.000198	0.000193
Middle Eastern	0.000163	0.000163
South Asian	0.000196	0.000196
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the conversion of 3-methylglutaconyl-CoA to 3- hydroxy-3-methylglutaryl-CoA (PubMed:11738050, PubMed:12434311, PubMed:12655555). Also has itaconyl-CoA hydratase activity by converting itaconyl-CoA into citramalyl-CoA in the C5- dicarboxylate catabolism pathway (PubMed:29056341). The C5- dicarboxylate catabolism pathway is required to detoxify itaconate, a vitamin B12-poisoning metabolite (PubMed:29056341). Has very low enoyl-CoA hydratase activity (PubMed:7892223). Was originally identified as RNA-binding protein that binds in vitro to clustered 5'-AUUUA-3' motifs (PubMed:7892223). {ECO:0000269|PubMed:11738050, ECO:0000269|PubMed:12434311, ECO:0000269|PubMed:12655555, ECO:0000269|PubMed:7892223, ECO:0000303|PubMed:29056341}.
• Disease: DISEASE: 3-methylglutaconic aciduria 1 (MGA1) [MIM:250950]: An inborn error of leucine metabolism. It leads to an autosomal recessive syndrome with variable clinical phenotype, ranging from delayed speech development to severe psychomotor retardation, coma, failure to thrive, metabolic acidosis and dystonia. MGA1 can be distinguished from other forms of MGA by the pattern of metabolite excretion: 3-methylglutaconic acid levels are higher than those detected in other forms, whereas methylglutaric acid levels are usually only slightly elevated and there is a high level of 3-hydroxyisovaleric acid excretion (not present in other MGA forms). {ECO:0000269|PubMed:12655555}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Valine, leucine and isoleucine degradation - Homo sapiens (human);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;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;Amino Acid metabolism;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: 0.333

Intolerance Scores

• loftool: 0.801
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• pHI: 0.131
• hipred: N
• hipred_score: 0.331
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.770

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Auh

Zebrafish Information Network

• Gene name: auh
• Affected structure: leucine metabolic process
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: leucine catabolic process;fatty acid beta-oxidation;branched-chain amino acid catabolic process
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: mRNA 3'-UTR binding;enoyl-CoA hydratase activity;methylglutaconyl-CoA hydratase activity;itaconyl-CoA hydratase activity