ALOX15B

protein-coding

arachidonate 15-lipoxygenase type B, the group of Arachidonate lipoxygenases

Gene summary

This gene encodes a member of the lipoxygenase family of structurally related nonheme iron dioxygenases involved in the production of fatty acid hydroperoxides. The encoded protein converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while metabolizing linoleic acid less effectively. This gene is located in a cluster of related genes and a pseudogene that spans approximately 100 kilobases on the short arm of chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001141.3

Inheritance

—

ClinVar variants

U:121B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr17:8,039,034-8,049,134

External References & Databases

Ensembl (ENSG00000179593)

Transcript & Mutation Effects

hg38 • Region Span ~10.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ALOX15B variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 121

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001141.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar		3
missense			118 clinvar	8 clinvar	1 clinvar	127
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	121	10	1	132

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001141.3	RefSeq	NP_001132.2	14	MANE Select
ENST00000380183.9	Ensembl	ENSP00000369530.4	14	MANE Select
NM_001039130.2	RefSeq	NP_001034219.1	13	Standard
NM_001039131.2	RefSeq	NP_001034220.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Serotonergic synapse - Homo sapiens (human)
Arachidonic acid metabolism - Homo sapiens (human)
Etodolac Action Pathway
Ketoprofen Action Pathway
Ibuprofen Action Pathway

Biological Process

lipid metabolic process
apoptotic process
negative regulation of cell population proliferation
positive regulation of macrophage derived foam cell differentiation
arachidonic acid metabolic process

Molecular Function

iron ion binding
calcium ion binding
lipid binding
linoleate 13S-lipoxygenase activity
arachidonate 8(S)-lipoxygenase activity

Cellular Component

nucleus
cytosol
cytoskeleton
plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380183
Coding exons: 14
Length: 10118
Individuals with no LoFs: 125389
Homozygous LoFs: 0
Heterozygous LoFs: 359
Defined: 125748
p: 0.00143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.272	383	398	0.962	0.0000228	4349
Missense (PolyPhen)		165	160.53	1.0278		1849
Synonymous	1.42	145	168	0.861	0.00000968	1377
Loss of Function	0.689	30	34.4	0.873	0.00000175	350

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0028	0.0027	notable
Latino/Admixed American	0.0014	0.0014	notable
Ashkenazi Jewish	0.0019	0.0019	notable
East Asian	0.0014	0.0014	notable
Finnish	0.0010	0.0010	notable
European (Non-Finnish)	0.0015	0.0015	notable
South Asian	0.00056	0.00056	rare
Other	0.0021	0.0021	notable

dbNSFP Gene Annotations

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. Converts arachidonic acid to 15S- hydroperoxyeicosatetraenoic acid/(15S)-HPETE. Also acts on linoleic acid to produce 13-hydroxyoctadecadienoic acid/13-HPODE. Has no detectable 8S-lipoxygenase activity but reacts with (8S)- HPETE to produce (8S,15S)-diHPETE. May regulate progression through the cell cycle and cell proliferation. May also regulate cytokine secretion by macrophages and therefore play a role in the immune response. May also regulate macrophage differentiation into proatherogenic foam cells. {ECO:0000269|PubMed:10625675, ECO:0000269|PubMed:11839751, ECO:0000269|PubMed:12704195, ECO:0000269|PubMed:16112079, ECO:0000269|PubMed:18067895, ECO:0000269|PubMed:22912809, ECO:0000269|PubMed:24497644}.;

Intolerance Scores

LoFtool: 0.0984
RVIS EVS: 0.98
RVIS percentile EVS: 90.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.706

Gene Damage Prediction

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