GeneBe

ALOX12B

protein-coding

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

Gene summary

This gene encodes an enzyme involved in the conversion of arachidonic acid to 12R-hydroxyeicosatetraenoic acid. Mutations in this gene are associated with nonbullous congenital ichthyosiform erythroderma. [provided by RefSeq, Sep 2015]

MANE transcript

NM_001139.3

Inheritance

AR

ClinVar variants

P:156U:155B:47

Top phenotype

Ichthyosis, congenital, autosomal recessive 2

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr17:8,072,636-8,087,716

External References & Databases

Ensembl (ENSG00000179477)NCBI Gene (242)OMIM (603741)HGNC:430GenCCUniProt (O75342)AlphaFoldClinVar (ALOX12B)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~15.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

self-healing collodion babySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017267

Submitter: Orphanet

congenital non-bullous ichthyosiform erythrodermaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019306

Submitter: Orphanet

autosomal recessive congenital ichthyosis 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009439

Submitter: Labcorp Genetics (formerly Invitae)

congenital non-bullous ichthyosiform erythrodermaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0019306

Submitter: Genomics England PanelApp

autosomal recessive congenital ichthyosis 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009439

Submitter: Genomics England PanelApp

lamellar ichthyosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017778

Submitter: Orphanet

autosomal recessive congenital ichthyosis 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009439

Submitter: PanelApp Australia

autosomal recessive congenital ichthyosis 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009439

Submitter: G2P

Clinical Genomic Database (CGD)

Ichthyosis, congenital, autosomal recessive 2AR

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 11773004; 16116617; 20301593Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ALOX12B variants in ClinVar

14 Conditions Cataloged
Autosomal recessive congenital ichthyosis 2Total: 208
not providedTotal: 171
Inborn genetic diseasesTotal: 75
ALOX12B-related disorderTotal: 32
not specifiedTotal: 30
Lamellar ichthyosisTotal: 20
Ichthyosis and erythrokeratodermaTotal: 7
Leukoencephalopathy with calcifications and cystsTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001139.3. 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.

EffectPLPVUSLBBSum
synonymous
8
clinvar
34
clinvar
3
clinvar
 45
missense
44
clinvar
39
clinvar
145
clinvar
9
clinvar
1
clinvar
 238
nonsense
14
clinvar
6
clinvar
1
clinvar
 21
start loss
1
clinvar
 1
frameshift
27
clinvar
9
clinvar
 36
splice donor/acceptor (+/-2bp)
9
clinvar
7
clinvar
1
clinvar
 17
Total9462155434358

Highest pathogenic variant AF is 0.0001226819

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001139.3RefSeqNP_001130.115MANE Select
ENST00000647874.1EnsemblENSP00000497784.115MANE Select
ENST00000649809.1EnsemblENSP00000496845.18Standard
ENST00001135832.1EnsemblENSP00000815156.115Standard

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

  • protein lipidation
  • sphingolipid metabolic process
  • positive regulation of gene expression
  • arachidonic acid metabolic process
  • lipoxygenase pathway

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

Cellular Component

  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000319144
Coding exons
15
Length
15068
Individuals with no LoFs
125692
Homozygous LoFs
0
Heterozygous LoFs
56
Defined
125748
p
0.000223
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.403264060.8040.00002384553
Missense (PolyPhen)1031570.656041751
Synonymous0.5991581680.9410.00001011395
Loss of Function3.631235.20.3400.00000169400

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.0000870.000087rare
Ashkenazi Jewish00.0absent
East Asian0.000170.00016rare
Finnish00.0absent
European (Non-Finnish)0.000270.00026rare
South Asian0.000590.00056rare
Other0.000160.00016rare

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. 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}.;

Intolerance Scores

LoFtool
0.257
RVIS EVS
-0.62
RVIS percentile EVS
17.4

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.389

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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