ALDH3A2

aldehyde dehydrogenase 3 family member A2, the group of Aldehyde dehydrogenases

Basic information

Region (hg38): 17:19648135-19685760

Previous symbols: [ "SLS", "ALDH10" ]

Links

ENSG00000072210 ∙ NCBI:224 ∙ OMIM:609523 ∙ HGNC:403 ∙ Uniprot:P51648 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Sjogren-Larsson syndrome (Definitive), mode of inheritance: AR
• Sjogren-Larsson syndrome (Definitive), mode of inheritance: AR
• Sjogren-Larsson syndrome (Strong), mode of inheritance: AR
• Sjogren-Larsson syndrome (Strong), mode of inheritance: AR
• Sjogren-Larsson syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Sjogren-Larsson syndrome	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; Dermatologic; Neurologic; Ophthalmologic	13354244; 13457946; 8176565; 9027499; 9829906; 11124298; 11408337; 16476818; 21684788; 21872273; 22397046; 22426667; 22833178; 23034980; 25784589; 31512987
Medical treatment (eg, with Zileuton) may be beneficial for certain aspects

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALDH3A2 gene.

• not provided (387 variants)
• Sjögren-Larsson syndrome (197 variants)
• Inborn genetic diseases (28 variants)
• not specified (10 variants)
• ALDH3A2-related condition (3 variants)
• - (2 variants)
• Cerebral palsy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALDH3A2 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			1	123	1	125
missense	2	19	70	8		99
nonsense	8	18				26
start loss		5				5
frameshift	25	28	3	1		57
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)	6	17	1	1		25
splice region		1	5	31	1	38
non coding		1	41	47	29	118
Total	42	88	118	180	30

Highest pathogenic variant AF is 0.0000591

Variants in ALDH3A2

This is a list of pathogenic ClinVar variants found in the ALDH3A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-19648599-G-C			Likely benign (Apr 09, 2021)
17-19648739-T-C			Likely benign (May 28, 2021)
17-19648757-C-T		Sjögren-Larsson syndrome	Uncertain significance (Jan 12, 2018)
17-19648818-G-A		Sjögren-Larsson syndrome	Benign (Jan 12, 2018)
17-19648823-C-G		Sjögren-Larsson syndrome	Likely benign (Jan 12, 2018)
17-19648875-G-A		Sjögren-Larsson syndrome	Uncertain significance (Jan 13, 2018)
17-19648905-C-T		Sjögren-Larsson syndrome	Uncertain significance (Jan 12, 2018)
17-19648961-A-G		Sjögren-Larsson syndrome	Uncertain significance (Jul 07, 2021)
17-19648969-G-A		Sjögren-Larsson syndrome	Uncertain significance (Jan 12, 2018)
17-19648972-A-G		Sjögren-Larsson syndrome	Likely pathogenic (May 02, 2017)
17-19648972-A-T		Sjögren-Larsson syndrome	Likely pathogenic (Jan 19, 2023)
17-19648973-T-A		Sjögren-Larsson syndrome	Pathogenic/Likely pathogenic (Apr 07, 2023)
17-19648974-G-A		Sjögren-Larsson syndrome	Likely pathogenic (May 02, 2017)
17-19648974-G-C		Sjögren-Larsson syndrome	Pathogenic/Likely pathogenic (Jan 04, 2024)
17-19648981-G-T		Sjögren-Larsson syndrome	Likely pathogenic (-)
17-19648986-C-G			Likely benign (Oct 20, 2023)
17-19648987-C-T			Uncertain significance (Jun 08, 2022)
17-19648991-GGGTCCGACAGGCGTTCCTGTCCGGCC-G		Sjögren-Larsson syndrome	Pathogenic/Likely pathogenic (Oct 04, 2023)
17-19648998-A-T			Likely benign (May 31, 2023)
17-19648997-G-GAC			Pathogenic (Jun 14, 2022)
17-19648999-C-G		Sjögren-Larsson syndrome • ALDH3A2-related disorder	Conflicting classifications of pathogenicity (Jan 31, 2024)
17-19648999-C-T		Sjögren-Larsson syndrome	Conflicting classifications of pathogenicity (Jun 01, 2023)
17-19649000-A-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
17-19649007-C-T			Likely benign (Aug 03, 2021)
17-19649008-C-T			Likely benign (Dec 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALDH3A2	protein_coding	protein_coding	ENST00000339618	10	29463

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000941	0.986	125681	0	67	125748	0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.682	245	277	0.885	0.0000151	3313
Missense in Polyphen		63	94.204	0.66876		1141
Synonymous	1.53	85	105	0.810	0.00000597	1007
Loss of Function	2.21	12	23.6	0.509	0.00000111	293

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000937	0.000937
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000237	0.000237
Middle Eastern	0.000218	0.000217
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length (PubMed:9133646, PubMed:22633490, PubMed:25047030). Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid (PubMed:22633490). {ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:25047030, ECO:0000269|PubMed:9133646}.
• Pathway: Tryptophan metabolism - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Arginine and proline metabolism - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Glycerolipid metabolism - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Lysine degradation - Homo sapiens (human);Histidine metabolism - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);Ascorbate and aldarate metabolism - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Refsum Disease;Phytanic Acid Peroxisomal Oxidation;Tryptophan metabolism;Metabolism of lipids;ethanol degradation II;Glutamate Glutamine metabolism;dopamine degradation;Tyrosine metabolism;Alpha-oxidation of phytanate;Leukotriene metabolism;Peroxisomal lipid metabolism;Metabolism;Lysine degradation;oxidative ethanol degradation III;ethanol degradation IV;Fatty acid metabolism;Propanoate metabolism;fatty acid α-oxidation III;tryptophan degradation via tryptamine;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Bile acid biosynthesis;Glycerophospholipid metabolism;Arginine Proline metabolism;fatty acid α-oxidation;Pyruvate metabolism;phenylethylamine degradation I;serotonin degradation;Tryptophan degradation;superpathway of tryptophan utilization;phytol degradation;Sphingolipid de novo biosynthesis;Valine Leucine Isoleucine degradation;noradrenaline and adrenaline degradation;Sphingolipid metabolism;Histidine degradation;putrescine degradation III (Consensus)

Recessive Scores

• pRec: 0.338

Intolerance Scores

• loftool: 0.251
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.36

Haploinsufficiency Scores

• pHI: 0.0720
• hipred: N
• hipred_score: 0.372
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.397

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aldh3a2
• 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: fatty acid alpha-oxidation;cellular aldehyde metabolic process;central nervous system development;peripheral nervous system development;epidermis development;sphingolipid biosynthetic process;phytol metabolic process;hexadecanal metabolic process;oxidation-reduction process
• Cellular component: peroxisomal membrane;endoplasmic reticulum membrane;integral component of membrane;intracellular membrane-bounded organelle
• Molecular function: 3-chloroallyl aldehyde dehydrogenase activity;aldehyde dehydrogenase (NAD) activity;protein binding;protein homodimerization activity;glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity;long-chain-alcohol oxidase activity;long-chain-aldehyde dehydrogenase activity;medium-chain-aldehyde dehydrogenase activity