ALDH1A2

aldehyde dehydrogenase 1 family member A2, the group of Aldehyde dehydrogenases

Basic information

Region (hg38): 15:57953423-58497866

Links

ENSG00000128918 ∙ NCBI:8854 ∙ OMIM:603687 ∙ HGNC:15472 ∙ Uniprot:O94788 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• diaphragmatic hernia 4, with cardiovascular defects (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diaphragmatic hernia 4, with cardiovascular defects	AR	Cardiovascular	The condition may involve complex cardiovascular anomalies, and awareness may allow early surgical and related management if indicated	Cardiovascular; Craniofacial; Musculoskeletal	33565183

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALDH1A2 gene.

• not provided (36 variants)
• Inborn genetic diseases (9 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALDH1A2 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	1	5
missense			10	1	1	12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					28	28
Total	0	0	10	5	30

Variants in ALDH1A2

This is a list of pathogenic ClinVar variants found in the ALDH1A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-57955212-G-C			Likely benign (Mar 28, 2018)
15-57955213-G-A		not specified	Uncertain significance (Feb 10, 2022)
15-57955214-G-C		not specified	Uncertain significance (Oct 04, 2022)
15-57955233-C-G		not specified	Uncertain significance (Apr 25, 2023)
15-57955251-C-T		ALDH1A2-related disorder	Likely benign (Oct 01, 2023)
15-57955365-C-G			Benign (Nov 10, 2018)
15-57955467-AAAG-A			Benign (Jun 18, 2021)
15-57960536-C-T			Benign (Jun 18, 2021)
15-57960653-G-A			Benign (Jun 18, 2021)
15-57960760-T-G			Benign (Dec 31, 2019)
15-57960864-C-T			Benign (Nov 10, 2018)
15-57960908-T-C			Benign (Nov 10, 2018)
15-57961071-T-G			Benign (Nov 10, 2018)
15-57961164-G-C		not specified	Uncertain significance (Apr 28, 2023)
15-57961164-G-T		Diaphragmatic hernia 4, with cardiovascular defects	Pathogenic (Sep 01, 2022)
15-57961292-G-T		ALDH1A2-related disorder	Benign (Dec 31, 2019)
15-57961782-CTAA-C			Benign (Jun 18, 2021)
15-57961980-T-A			Benign (Jun 18, 2021)
15-57962028-C-T			Likely benign (Jul 30, 2018)
15-57962116-C-T		Diaphragmatic hernia 4, with cardiovascular defects	Pathogenic (Sep 01, 2022)
15-57962117-G-A			Likely benign (Apr 01, 2023)
15-57962136-T-C		not specified	Uncertain significance (Feb 06, 2024)
15-57962154-T-C		not specified	Uncertain significance (Jan 03, 2024)
15-57963908-G-A		not specified	Uncertain significance (Mar 12, 2024)
15-57963931-C-T		Diaphragmatic hernia 4, with cardiovascular defects	Pathogenic (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALDH1A2	protein_coding	protein_coding	ENST00000249750	13	544444

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.363	0.637	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.44	215	283	0.759	0.0000153	3399
Missense in Polyphen		83	146.21	0.56767		1799
Synonymous	-1.75	128	105	1.22	0.00000572	1010
Loss of Function	3.69	6	26.5	0.226	0.00000130	325

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000651	0.0000615
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Does metabolize octanal and decanal but does not metabolize citral, benzaldehyde, acetaldehyde and propanal efficiently (By similarity). {ECO:0000250}.
• Pathway: Retinol metabolism - Homo sapiens (human);Vitamin A Deficiency;Retinol Metabolism;Ethanol effects on histone modifications;Tryptophan metabolism;Vitamin A and Carotenoid Metabolism;Signal Transduction;RA biosynthesis pathway;Lysine degradation;Propanoate metabolism;retinoate biosynthesis I;Pyruvate metabolism;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;Tryptophan degradation;Valine Leucine Isoleucine degradation;Histidine degradation (Consensus)

Recessive Scores

• pRec: 0.220

Intolerance Scores

• loftool: 0.302
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24.33

Haploinsufficiency Scores

• pHI: 0.423
• hipred: Y
• hipred_score: 0.662
• ghis: 0.490

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.835

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aldh1a2
• Phenotype: craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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; vision/eye 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); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; respiratory system phenotype; embryo phenotype

Zebrafish Information Network

• Gene name: aldh1a2
• Affected structure: hyohyoideus
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: blood vessel development;kidney development;liver development;regulation of endothelial cell proliferation;heart morphogenesis;vitamin A metabolic process;midgut development;positive regulation of cell population proliferation;negative regulation of cell population proliferation;determination of bilateral symmetry;proximal/distal pattern formation;positive regulation of gene expression;neural crest cell development;morphogenesis of embryonic epithelium;neural tube development;pituitary gland development;neuron differentiation;lung development;hindbrain development;pancreas development;embryonic camera-type eye development;response to estradiol;response to vitamin A;response to cytokine;embryonic forelimb morphogenesis;ureter maturation;retinol metabolic process;retinoic acid metabolic process;retinal metabolic process;9-cis-retinoic acid biosynthetic process;positive regulation of apoptotic process;embryonic digestive tract development;cardiac muscle tissue development;oxidation-reduction process;face development;cellular response to retinoic acid;retinoic acid receptor signaling pathway involved in somitogenesis
• Cellular component: cytoplasm;cytosol;perinuclear region of cytoplasm
• Molecular function: retinal dehydrogenase activity;3-chloroallyl aldehyde dehydrogenase activity;aldehyde dehydrogenase (NAD) activity;retinal binding