ALOXE3

arachidonate lipoxygenase 3, the group of Arachidonate lipoxygenases

Basic information

Region (hg38): 17:8095900-8119047

Links

ENSG00000179148 ∙ NCBI:59344 ∙ OMIM:607206 ∙ HGNC:13743 ∙ Uniprot:Q9BYJ1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive congenital ichthyosis 3 (Strong), mode of inheritance: AR
• congenital non-bullous ichthyosiform erythroderma (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 3 (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 3 (Strong), mode of inheritance: AR
• lamellar ichthyosis (Supportive), mode of inheritance: AR
• congenital non-bullous ichthyosiform erythroderma (Supportive), mode of inheritance: AR
• self-healing collodion baby (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis, congenital, autosomal recessive 3	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	Dermatologic	11773004; 16116617; 19131948; 20301593

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALOXE3 gene.

• not provided (9 variants)
• Autosomal recessive congenital ichthyosis 3 (7 variants)
• Lamellar ichthyosis (4 variants)
• ALOXE3-related disorder (3 variants)
• Autosomal recessive congenital ichthyosis 2 (2 variants)
• Congenital nonbullous ichthyosiform erythroderma (1 variants)
• 30 conditions (1 variants)
• Autosomal recessive congenital ichthyosis (1 variants)
• Ichthyosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALOXE3 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			6	7	4	17
missense	1	5	67	5	2	80
nonsense	9	1				10
start loss						0
frameshift	3		1			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	5	1			7
splice region			4	2		6
non coding			20	10	40	70
Total	14	11	96	22	46

Highest pathogenic variant AF is 0.00100

Variants in ALOXE3

This is a list of pathogenic ClinVar variants found in the ALOXE3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-8095934-C-A		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8095958-A-C		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8095973-G-A		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8095986-G-A		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 12, 2018)
17-8096009-A-G		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8096089-C-T		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8096104-T-C		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8096113-A-C		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8096146-C-T		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 12, 2018)
17-8096161-C-T		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8096235-C-T		Autosomal recessive congenital ichthyosis 3	Likely benign (Jan 13, 2018)
17-8096236-G-T		Autosomal recessive congenital ichthyosis 3	Benign (Jan 13, 2018)
17-8096271-T-G		Autosomal recessive congenital ichthyosis 3	Benign (Jan 13, 2018)
17-8096283-G-A		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8096313-A-T		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8096365-G-A		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8096405-G-C		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 13, 2018)
17-8096466-G-A		Autosomal recessive congenital ichthyosis 3	Uncertain significance (Jan 12, 2018)
17-8096516-A-G		Autosomal recessive congenital ichthyosis 3	Benign (Jan 12, 2018)
17-8096540-G-A		Autosomal recessive congenital ichthyosis 3	Likely benign (Jan 12, 2018)
17-8096603-T-C		Autosomal recessive congenital ichthyosis 3	Benign (Jan 13, 2018)
17-8096626-G-T		ALOXE3-related disorder	Likely benign (Jun 27, 2019)
17-8096638-C-T		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
17-8096639-G-A		not specified • Autosomal recessive congenital ichthyosis 3	Benign (Jan 29, 2024)
17-8096649-A-G		ALOXE3-related disorder	Likely benign (Oct 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALOXE3	protein_coding	protein_coding	ENST00000318227	16	23148

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.13e-20	0.0761	125636	0	112	125748	0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.149	471	480	0.981	0.0000276	5441
Missense in Polyphen		145	160.07	0.90586		1963
Synonymous	0.414	196	204	0.963	0.0000116	1717
Loss of Function	1.26	35	44.0	0.795	0.00000235	458

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000507	0.000507
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000870	0.000870
Finnish	0.000417	0.000416
European (Non-Finnish)	0.000520	0.000519
Middle Eastern	0.000870	0.000870
South Asian	0.000426	0.000425
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced dioxygenase activity compared to other lipoxygenases. The hydroperoxide isomerase activity catalyzes the isomerization of hydroperoxides, derived from arachidonic and linoleic acid by ALOX12B, into hepoxilin-type epoxyalcohols. The dioxygenase activity requires a step of activation of the enzyme by molecular oxygen. In presence of oxygen, oxygenates polyunsaturated fatty acids, including arachidonic acid, to produce fatty acid hydroperoxides. In the skin, acts downstream of ALOX12B on the linoleate moiety of esterified omega-hydroxyacyl- sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins. Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss. In parallel, it may have a signaling function in barrier formation through the production of hepoxilins metabolites. Plays also a role in adipocyte differentiation through hepoxilin A3 and hepoxilin B3 production which in turn activate PPARG. Through the production of hepoxilins in the spinal cord, it may regulate inflammatory tactile allodynia. {ECO:0000269|PubMed:12881489, ECO:0000269|PubMed:17045234, ECO:0000269|PubMed:20921226, ECO:0000269|PubMed:20923767, ECO:0000269|PubMed:21558561}.
• Pathway: Metabolism of lipids;Synthesis of 12-eicosatetraenoic acid derivatives;Arachidonic acid metabolism;Metabolism;Fatty acid metabolism (Consensus)

Recessive Scores

• pRec: 0.154

Intolerance Scores

• loftool: 0.146
• rvis_EVS: -1
• rvis_percentile_EVS: 8.54

Haploinsufficiency Scores

• pHI: 0.0993
• hipred: N
• hipred_score: 0.180
• ghis: 0.579

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.447

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aloxe3
• 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); homeostasis/metabolism phenotype; growth/size/body region 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: sphingolipid metabolic process;sensory perception of pain;arachidonic acid metabolic process;lipoxygenase pathway;peroxisome proliferator activated receptor signaling pathway;linoleic acid metabolic process;fat cell differentiation;ceramide biosynthetic process;hepoxilin biosynthetic process;oxidation-reduction process;establishment of skin barrier
• Cellular component: cytosol
• Molecular function: iron ion binding;protein binding;oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen;lyase activity;hepoxilin A3 synthase activity