ALDH1A3

aldehyde dehydrogenase 1 family member A3, the group of Aldehyde dehydrogenases

Basic information

Region (hg38): 15:100877713-100916626

Previous symbols: [ "ALDH6" ]

Links

ENSG00000184254 ∙ NCBI:220 ∙ OMIM:600463 ∙ HGNC:409 ∙ Uniprot:P47895 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated microphthalmia 8 (Strong), mode of inheritance: AR
• isolated microphthalmia 8 (Strong), mode of inheritance: AR
• isolated anophthalmia-microphthalmia syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia, isolated 8	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	Neurologic; Ophthalmologic	23312594

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALDH1A3 gene.

• not provided (59 variants)
• Isolated microphthalmia 8 (45 variants)
• Inborn genetic diseases (9 variants)
• not specified (3 variants)
• Isolated anophthalmia-microphthalmia syndrome (3 variants)
• Microphthalmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALDH1A3 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				19	5	24
missense	2	6	17	4	1	30
nonsense	1	1				2
start loss						0
frameshift	3		1			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2					2
splice region	1			2	2	5
non coding				16	26	42
Total	8	7	19	39	32

Highest pathogenic variant AF is 0.0000131

Variants in ALDH1A3

This is a list of pathogenic ClinVar variants found in the ALDH1A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-100879560-T-A			Benign (Aug 03, 2018)
15-100879582-G-A			Benign (Nov 10, 2018)
15-100879640-G-A			Benign (Aug 03, 2018)
15-100879926-G-C		Inborn genetic diseases	Uncertain significance (May 17, 2023)
15-100879933-A-T		Inborn genetic diseases	Uncertain significance (Aug 08, 2023)
15-100879950-A-G		Isolated microphthalmia 8 • ALDH1A3-related disorder	Benign/Likely benign (Dec 26, 2023)
15-100880013-C-A		ALDH1A3-related disorder	Likely benign (May 08, 2019)
15-100880021-C-T		Isolated microphthalmia 8	Likely benign (Mar 28, 2023)
15-100880135-G-A			Likely benign (Jul 01, 2022)
15-100880138-C-G			Likely benign (Jul 01, 2022)
15-100885138-G-A			Likely benign (Dec 09, 2018)
15-100885265-A-G		Isolated microphthalmia 8	Pathogenic (Sep 01, 2022)
15-100885290-C-G		Isolated microphthalmia 8 • ALDH1A3-related disorder	Likely benign (Sep 11, 2023)
15-100885337-G-A		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
15-100885351-G-T			Likely pathogenic (Dec 01, 2016)
15-100885376-A-C		Isolated microphthalmia 8	Benign (Jan 09, 2023)
15-100885414-G-T			Benign (Mar 06, 2019)
15-100885498-T-C			Benign (Jun 19, 2018)
15-100885522-G-A			Likely benign (Dec 09, 2018)
15-100885655-C-CT			Benign (Sep 01, 2020)
15-100885655-C-CTT			Benign (Jun 18, 2021)
15-100887320-GTCAAAAGATGACACCCAAACTGCAGTCACCTCAAAAGATGACACCCAAACTGCAGTCACC-G			Likely benign (Sep 11, 2018)
15-100887380-C-G			Likely benign (Sep 11, 2018)
15-100887396-G-C			Likely benign (Aug 14, 2018)
15-100887515-C-T			Likely benign (Feb 22, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALDH1A3	protein_coding	protein_coding	ENST00000329841	13	38913

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.141	0.859	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.24	192	301	0.637	0.0000180	3324
Missense in Polyphen		72	145.35	0.49537		1536
Synonymous	0.0733	122	123	0.992	0.00000828	1020
Loss of Function	3.31	6	23.2	0.259	9.79e-7	306

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000299	0.0000299
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000536	0.0000527
Middle Eastern	0.000163	0.000163
South Asian	0.0000983	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: NAD-dependent aldehyde dehydrogenase that catalyzes the formation of retinoic acid (PubMed:27759097). Has high activity with all-trans retinal, and has much lower in vitro activity with acetaldehyde (PubMed:27759097). Required for the biosynthesis of normal levels of retinoic acid in the embryonic ocular and nasal regions; retinoic acid is required for normal embryonic development of the eye and the nasal region (By similarity). {ECO:0000250|UniProtKB:Q9JHW9, ECO:0000269|PubMed:27759097}.
• Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Phenylalanine metabolism - Homo sapiens (human);Histidine metabolism - Homo sapiens (human);Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Drug metabolism - cytochrome P450 - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Tyrosine metabolism - Homo sapiens (human);Ethanol effects on histone modifications;Vitamin A and Carotenoid Metabolism;Signal Transduction;RA biosynthesis pathway;Phenylalanine degradation;retinoate biosynthesis I;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;Tyrosine metabolism;Histidine degradation (Consensus)

Recessive Scores

• pRec: 0.268

Intolerance Scores

• loftool: 0.606
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.72

Haploinsufficiency Scores

• pHI: 0.257
• hipred: Y
• hipred_score: 0.738
• ghis: 0.402

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.715

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aldh1a3
• Phenotype: renal/urinary system phenotype; skeleton phenotype; vision/eye phenotype; digestive/alimentary 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); normal phenotype; respiratory system phenotype; embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: aldh1a3
• Affected structure: eye
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: optic cup morphogenesis involved in camera-type eye development;retinoic acid biosynthetic process;locomotory behavior;nucleus accumbens development;embryonic camera-type eye development;inner ear morphogenesis;retinol metabolic process;retinoic acid metabolic process;retinal metabolic process;positive regulation of apoptotic process;embryonic eye morphogenesis;neuromuscular process controlling balance;protein homotetramerization;oxidation-reduction process;righting reflex;olfactory pit development;face development;Harderian gland development
• Cellular component: nucleus;cytoplasm;cytosol;plasma membrane;extracellular exosome
• Molecular function: retinal dehydrogenase activity;aldehyde dehydrogenase (NAD) activity;aldehyde dehydrogenase [NAD(P)+] activity;protein homodimerization activity;thyroid hormone binding;NAD+ binding