ALDH5A1

aldehyde dehydrogenase 5 family member A1, the group of Aldehyde dehydrogenases

Basic information

Region (hg38): 6:24494866-24537207

Links

ENSG00000112294 ∙ NCBI:7915 ∙ OMIM:610045 ∙ HGNC:408 ∙ Uniprot:P51649 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• succinic semialdehyde dehydrogenase deficiency (Definitive), mode of inheritance: AR
• succinic semialdehyde dehydrogenase deficiency (Strong), mode of inheritance: AR
• succinic semialdehyde dehydrogenase deficiency (Supportive), mode of inheritance: AR
• succinic semialdehyde dehydrogenase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Succinic semialdehyde dehydrogenase deficiency	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	7226548; 6627675; 9266358; 9093300; 9683595; 12743223; 14635103; 15059623; 17438226; 20304328; 21612881; 22437753; 32887777

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALDH5A1 gene.

• Succinate-semialdehyde dehydrogenase deficiency (677 variants)
• not provided (167 variants)
• Inborn genetic diseases (26 variants)
• not specified (23 variants)
• Intellectual disability (3 variants)
• ALDH5A1-related condition (2 variants)
• Seizure (2 variants)
• Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
• EEG abnormality (1 variants)
• See cases (1 variants)
• Seizure;Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALDH5A1 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	115	4	121
missense	13	40	234	6	4	297
nonsense	13	6				19
start loss			1			1
frameshift	31	10				41
inframe indel	3	1	4			8
splice donor/acceptor (+/-2bp)	10	4				14
splice region			9	15	4	28
non coding	1		54	62	57	174
Total	71	61	295	183	65

Highest pathogenic variant AF is 0.0000858

Variants in ALDH5A1

This is a list of pathogenic ClinVar variants found in the ALDH5A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-24494888-C-T			Likely benign (Sep 16, 2018)
6-24494988-G-A		ALDH5A1-related disorder	Likely benign (Mar 15, 2019)
6-24494998-T-C		Succinate-semialdehyde dehydrogenase deficiency	Uncertain significance (Mar 19, 2022)
6-24495001-C-T		Succinate-semialdehyde dehydrogenase deficiency	Uncertain significance (Oct 24, 2022)
6-24495006-T-G		not specified • Succinate-semialdehyde dehydrogenase deficiency • ALDH5A1-related disorder	Benign/Likely benign (Feb 01, 2024)
6-24495008-C-T		Succinate-semialdehyde dehydrogenase deficiency	Likely benign (Dec 09, 2023)
6-24495009-A-G		Succinate-semialdehyde dehydrogenase deficiency • Seizure • not specified	Conflicting classifications of pathogenicity (Jan 30, 2024)
6-24495014-G-T		Succinate-semialdehyde dehydrogenase deficiency	Benign/Likely benign (Jan 29, 2024)
6-24495016-T-G		Succinate-semialdehyde dehydrogenase deficiency	Uncertain significance (Oct 18, 2022)
6-24495017-G-A		Succinate-semialdehyde dehydrogenase deficiency	Likely benign (Aug 16, 2022)
6-24495018-C-T		Succinate-semialdehyde dehydrogenase deficiency	Conflicting classifications of pathogenicity (Dec 21, 2023)
6-24495020-G-C		Succinate-semialdehyde dehydrogenase deficiency	Likely benign (Dec 29, 2021)
6-24495020-G-T		Succinate-semialdehyde dehydrogenase deficiency	Likely benign (Aug 17, 2023)
6-24495023-C-G		Succinate-semialdehyde dehydrogenase deficiency	Uncertain significance (Aug 30, 2021)
6-24495024-T-A		Succinate-semialdehyde dehydrogenase deficiency	Uncertain significance (Aug 10, 2022)
6-24495026-T-TG		Succinate-semialdehyde dehydrogenase deficiency	Pathogenic (Mar 07, 2022)
6-24495028-G-A		Succinate-semialdehyde dehydrogenase deficiency • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 14, 2023)
6-24495033-C-T		Succinate-semialdehyde dehydrogenase deficiency	Uncertain significance (Aug 20, 2022)
6-24495038-C-T		Succinate-semialdehyde dehydrogenase deficiency	Likely benign (Sep 07, 2022)
6-24495040-T-G		Succinate-semialdehyde dehydrogenase deficiency	Uncertain significance (Mar 19, 2022)
6-24495042-G-A		Succinate-semialdehyde dehydrogenase deficiency	Uncertain significance (May 20, 2021)
6-24495042-G-C		Succinate-semialdehyde dehydrogenase deficiency	Uncertain significance (Dec 30, 2021)
6-24495046-C-T		Succinate-semialdehyde dehydrogenase deficiency • Inborn genetic diseases	Uncertain significance (Oct 28, 2022)
6-24495047-G-A		Succinate-semialdehyde dehydrogenase deficiency	Likely benign (Nov 11, 2020)
6-24495050-G-A		Succinate-semialdehyde dehydrogenase deficiency	Likely benign (Feb 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALDH5A1	protein_coding	protein_coding	ENST00000348925	11	42356

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.05e-7	0.930	125667	0	81	125748	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.734	254	289	0.879	0.0000162	3483
Missense in Polyphen		102	125.43	0.81322		1393
Synonymous	0.539	112	119	0.937	0.00000763	1152
Loss of Function	1.79	14	23.4	0.599	0.00000116	280

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000799	0.000799
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000431	0.000431
Middle Eastern	0.000109	0.000109
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). {ECO:0000269|PubMed:19300440}.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Butanoate metabolism - Homo sapiens (human);Valproic Acid Pathway, Pharmacodynamics;Pathway_PA165964473;Cyclophosphamide Pathway, Pharmacodynamics;2-Hydroxyglutric Aciduria (D And L Form);Homocarnosinosis;Hyperinsulinism-Hyperammonemia Syndrome;Succinic semialdehyde dehydrogenase deficiency;4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency;Glutamate Metabolism;Glutamate Glutamine metabolism;Neuronal System;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;GABA shunt;Degradation of GABA;GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Transmission across Chemical Synapses;4-aminobutyrate degradation (Consensus)

Recessive Scores

• pRec: 0.212

Intolerance Scores

• loftool: 0.331
• rvis_EVS: 0.4
• rvis_percentile_EVS: 76.36

Haploinsufficiency Scores

• pHI: 0.808
• hipred: Y
• hipred_score: 0.505
• ghis: 0.576

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aldh5a1
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype

Gene ontology

• Biological process: glucose metabolic process;acetate metabolic process;succinate metabolic process;glutamate metabolic process;glutamine metabolic process;glycerophospholipid metabolic process;glucosylceramide metabolic process;galactosylceramide metabolic process;glutathione metabolic process;central nervous system development;gamma-aminobutyric acid catabolic process;post-embryonic development;respiratory electron transport chain;neurotransmitter catabolic process;short-chain fatty acid metabolic process;protein homotetramerization
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: succinate-semialdehyde dehydrogenase (NAD+) activity;succinate-semialdehyde dehydrogenase [NAD(P)+] activity;protein homodimerization activity