ALDH6A1

aldehyde dehydrogenase 6 family member A1, the group of Aldehyde dehydrogenases

Basic information

Region (hg38): 14:74056846-74084492

Previous symbols: [ "MMSDH" ]

Links

ENSG00000119711 ∙ NCBI:4329 ∙ OMIM:603178 ∙ HGNC:7179 ∙ Uniprot:Q02252 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• methylmalonate semialdehyde dehydrogenase deficiency (Moderate), mode of inheritance: AR
• methylmalonate semialdehyde dehydrogenase deficiency (Strong), mode of inheritance: AR
• methylmalonate semialdehyde dehydrogenase deficiency (Supportive), mode of inheritance: AR
• methylmalonate semialdehyde dehydrogenase deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Methylmalonate semialdehyde dehydrogenase deficiency	AR	Biochemical	Dietary management (eg, with low-protein, valine restricted diet) has been reported as beneficial	Biochemical	3939535; 3117077; 9787093; 10947204; 21863277; 32151545
Some individuals have been reported as asymptomatic

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALDH6A1 gene.

• Methylmalonate semialdehyde dehydrogenase deficiency (102 variants)
• not provided (93 variants)
• Inborn genetic diseases (18 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALDH6A1 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			4	14	1	19
missense			56	2	1	59
nonsense	1		1			2
start loss			1			1
frameshift		1	1			2
inframe indel			2			2
splice donor/acceptor (+/-2bp)			3			3
splice region			4	9	1	14
non coding			30	21	27	78
Total	1	1	98	37	29

Highest pathogenic variant AF is 0.0000132

Variants in ALDH6A1

This is a list of pathogenic ClinVar variants found in the ALDH6A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-74057648-T-G		Methylmalonate semialdehyde dehydrogenase deficiency	Benign (Jan 13, 2018)
14-74057781-G-A		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
14-74057826-A-G		Methylmalonate semialdehyde dehydrogenase deficiency	Benign (Jan 13, 2018)
14-74057868-C-G		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)
14-74057962-T-C		Methylmalonate semialdehyde dehydrogenase deficiency	Benign (Jan 13, 2018)
14-74058125-A-G		Methylmalonate semialdehyde dehydrogenase deficiency	Benign/Likely benign (Oct 08, 2021)
14-74058151-C-A		Methylmalonate semialdehyde dehydrogenase deficiency	Likely benign (Jan 12, 2018)
14-74058220-G-T		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Apr 06, 2018)
14-74058281-C-T		Methylmalonate semialdehyde dehydrogenase deficiency	Benign (Jan 13, 2018)
14-74058314-G-A		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
14-74058344-C-T		Methylmalonate semialdehyde dehydrogenase deficiency	Benign (Jan 13, 2018)
14-74058381-A-G		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
14-74058485-G-A		Methylmalonate semialdehyde dehydrogenase deficiency	Benign (Jan 13, 2018)
14-74058679-G-A		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)
14-74058704-T-C		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
14-74058708-A-G		Methylmalonate semialdehyde dehydrogenase deficiency	Benign (Jan 13, 2018)
14-74058738-C-G		Methylmalonate semialdehyde dehydrogenase deficiency	Likely benign (Jan 12, 2018)
14-74058755-T-G		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)
14-74058822-C-T		Methylmalonate semialdehyde dehydrogenase deficiency	Likely benign (Jan 12, 2018)
14-74058883-G-A		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
14-74058987-G-A		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)
14-74059019-G-A		Methylmalonate semialdehyde dehydrogenase deficiency	Benign (Jan 12, 2018)
14-74059040-C-T		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
14-74059041-G-A		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)
14-74059108-C-T		Methylmalonate semialdehyde dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALDH6A1	protein_coding	protein_coding	ENST00000553458	12	27644

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.56e-10	0.884	125688	0	59	125747	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	242	292	0.828	0.0000149	3474
Missense in Polyphen		114	142.76	0.79856		1698
Synonymous	1.28	87	104	0.839	0.00000505	1080
Loss of Function	1.79	19	29.5	0.644	0.00000184	315

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000540	0.000539
Ashkenazi Jewish	0.00	0.00
East Asian	0.000598	0.000598
Finnish	0.00	0.00
European (Non-Finnish)	0.000186	0.000185
Middle Eastern	0.000598	0.000598
South Asian	0.000327	0.000327
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in valine and pyrimidine metabolism. Binds fatty acyl-CoA.
• Disease: DISEASE: Methylmalonate semialdehyde dehydrogenase deficiency (MMSDHD) [MIM:614105]: A metabolic disorder characterized by elevated beta-alanine, 3-hydroxypropionic acid, and both isomers of 3-amino and 3-hydroxyisobutyric acids in urine organic acids. {ECO:0000269|PubMed:10947204}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Propanoate metabolism - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Carnosinuria, carnosinemia;Ureidopropionase deficiency;GABA-Transaminase Deficiency;3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Malonyl-coa decarboxylase deficiency;Beta-Alanine Metabolism;Malonic Aciduria;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Maple Syrup Urine Disease;Propanoate Metabolism;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;Methylmalonic Aciduria Due to Cobalamin-Related Disorders;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Beta-Ketothiolase Deficiency;Branched-chain amino acid catabolism;Metabolism of amino acids and derivatives;Metabolism;Propanoate metabolism;valine degradation;Valine, leucine and isoleucine degradation;Propanoate metabolism;Valine Leucine Isoleucine degradation;β-alanine degradation (Consensus)

Recessive Scores

• pRec: 0.217

Intolerance Scores

• loftool: 0.494
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.201
• hipred: N
• hipred_score: 0.379
• ghis: 0.477

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.915

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aldh6a1

Gene ontology

• Biological process: thymine catabolic process;valine metabolic process;valine catabolic process;branched-chain amino acid catabolic process;thymine metabolic process;brown fat cell differentiation;oxidation-reduction process
• Cellular component: nucleoplasm;mitochondrion;mitochondrial matrix
• Molecular function: fatty-acyl-CoA binding;RNA binding;methylmalonate-semialdehyde dehydrogenase (acylating) activity;malonate-semialdehyde dehydrogenase (acetylating) activity