ALOX12B

arachidonate 12-lipoxygenase, 12R type, the group of Arachidonate lipoxygenases

Basic information

Region (hg38): 17:8072636-8087716

Links

ENSG00000179477 ∙ NCBI:242 ∙ OMIM:603741 ∙ HGNC:430 ∙ Uniprot:O75342 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital non-bullous ichthyosiform erythroderma (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 2 (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 2 (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
• autosomal recessive congenital ichthyosis 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis, congenital, autosomal recessive 2	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; 20301593

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALOX12B gene.

• not provided (19 variants)
• Autosomal recessive congenital ichthyosis 2 (12 variants)
• Lamellar ichthyosis (3 variants)
• Ichthyosis (2 variants)
• ALOX12B-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALOX12B 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			7	12	3	22
missense	5	15	73	5	1	99
nonsense	6	2	1			9
start loss						0
frameshift	9	4				13
inframe indel	1	1	2			4
splice donor/acceptor (+/-2bp)	2	4				6
splice region	1		4	1	2	8
non coding			17	4	28	49
Total	23	26	100	21	32

Highest pathogenic variant AF is 0.000132

Variants in ALOX12B

This is a list of pathogenic ClinVar variants found in the ALOX12B region.

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

Position	Type	Phenotype	Significance	ClinVar
17-8072652-G-GT		Congenital ichthyosiform erythroderma	Uncertain significance (Jun 14, 2016)
17-8072670-T-C		Autosomal recessive congenital ichthyosis 2	Uncertain significance (Jan 12, 2018)
17-8072705-G-A		Autosomal recessive congenital ichthyosis 2	Benign (Jan 13, 2018)
17-8072783-G-T		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072789-C-G			Uncertain significance (Sep 08, 2023)
17-8072795-C-A		Autosomal recessive congenital ichthyosis 2	Uncertain significance (Apr 27, 2017)
17-8072811-T-C		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
17-8072813-G-C		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072817-T-C		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072836-T-A		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072839-T-TGCGCTGGCGGATGTCGTGTGAGATCTGGTTCAG		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072841-C-A		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072841-C-T		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072842-G-T		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072854-C-CGT		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072864-CT-C		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072865-T-C		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
17-8072877-T-G		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072890-C-CTAT			Uncertain significance (Sep 01, 2022)
17-8072899-TC-T		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072911-C-T		Autosomal recessive congenital ichthyosis 2	Uncertain significance (Jan 13, 2018)
17-8072914-C-T		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)
17-8072919-A-C		Autosomal recessive congenital ichthyosis 2	Uncertain significance (Sep 26, 2019)
17-8072936-G-C		Inborn genetic diseases	Uncertain significance (Apr 13, 2022)
17-8072939-T-TC		Autosomal recessive congenital ichthyosis 2	Pathogenic (Jan 07, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALOX12B	protein_coding	protein_coding	ENST00000319144	15	15068

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000756	0.999	125692	0	56	125748	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.40	326	406	0.804	0.0000238	4553
Missense in Polyphen		103	157	0.65604		1751
Synonymous	0.599	158	168	0.941	0.0000101	1395
Loss of Function	3.63	12	35.2	0.340	0.00000169	400

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.000170	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000265	0.000264
Middle Eastern	0.000170	0.000163
South Asian	0.000588	0.000555
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Mainly converts arachidonic acid to (12R)- hydroperoxyeicosatetraenoic acid/(12R)-HPETE and minor stereoisomers. In the skin, acts upstream of ALOXE3 on the lineolate 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. May also play a role in the regulation of the expression of airway mucins. {ECO:0000269|PubMed:21558561, ECO:0000269|PubMed:22441738, ECO:0000269|PubMed:9618483}.
• Pathway: Serotonergic synapse - Homo sapiens (human);Arachidonic acid metabolism - Homo sapiens (human);Etodolac Action Pathway;Ketoprofen Action Pathway;Ibuprofen Action Pathway;Rofecoxib Action Pathway;Acetylsalicylic Acid Action Pathway;Diflunisal Action Pathway;Leukotriene C4 Synthesis Deficiency;Acetaminophen Action Pathway;Celecoxib Action Pathway;Sulindac Action Pathway;Diclofenac Action Pathway;Ketorolac Action Pathway;Naproxen Action Pathway;Etoricoxib Action Pathway;Carprofen Action Pathway;Flurbiprofen Action Pathway;Fenoprofen Action Pathway;Antrafenine Action Pathway;Antipyrine Action Pathway;Lumiracoxib Action Pathway;Magnesium salicylate Action Pathway;Trisalicylate-choline Action Pathway;Nepafenac Action Pathway;Phenylbutazone Action Pathway;Lornoxicam Action Pathway;Salsalate Action Pathway;Tenoxicam Action Pathway;Tiaprofenic Acid Action Pathway;Tolmetin Action Pathway;Salicylic Acid Action Pathway;Salicylate-sodium Action Pathway;Oxaprozin Action Pathway;Valdecoxib Action Pathway;Nabumetone Action Pathway;Indomethacin Action Pathway;Meloxicam Action Pathway;Suprofen Action Pathway;Bromfenac Action Pathway;Mefenamic Acid Action Pathway;Arachidonic Acid Metabolism;Piroxicam Action Pathway;Metabolism of lipids;Synthesis of 12-eicosatetraenoic acid derivatives;Arachidonic acid metabolism;Metabolism;Fatty acid metabolism;IL23-mediated signaling events (Consensus)

Intolerance Scores

• loftool: 0.257
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.4

Haploinsufficiency Scores

• pHI: 0.207
• hipred: Y
• hipred_score: 0.630
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.389

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alox12b
• 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); homeostasis/metabolism 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)

Gene ontology

• Biological process: protein lipidation;sphingolipid metabolic process;positive regulation of gene expression;arachidonic acid metabolic process;lipoxygenase pathway;positive regulation of MAPK cascade;linoleic acid metabolic process;ceramide biosynthetic process;hepoxilin biosynthetic process;oxidation-reduction process;establishment of skin barrier;positive regulation of mucus secretion
• Cellular component: cytosol
• Molecular function: arachidonate 12-lipoxygenase activity;iron ion binding;protein binding;oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen;linoleate 9S-lipoxygenase activity