Autosomal recessive congenital ichthyosis 3

Summary

Autosomal recessive congenital ichthyosis 3 (MONDO:0011680) is a disease caused by ALOXE3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ALOXE3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 137

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive congenital ichthyosis 3
Mondo ID	MONDO:0011680
MeSH	C564699
OMIM	606545
DOID	DOID:0060711
UMLS	C3539888
MedGen	761665
GARD	0015393
Is cancer (heuristic)	no

Also known as: ARCI3 · autosomal recessive congenital ichthyosis type 3 · ichthyosis, congenital, autosomal recessive 3 · ichthyosis, congenital, autosomal recessive type 3 · ichthyosis, lamellar, 5

Data availability: 137 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › epidermal disease › ichthyosis › inherited ichthyosis › autosomal recessive congenital ichthyosis › self-healing collodion baby › autosomal recessive congenital ichthyosis 3

Related subtypes (1): autosomal recessive congenital ichthyosis 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

137 retrieved; paginated sample, class counts are floors:

46 uncertain significance, 35 pathogenic, 18 conflicting classifications of pathogenicity, 17 benign, 15 likely pathogenic, 3 benign/likely benign, 2 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323064	NM_021628.3(ALOXE3):c.1432del (p.Ser478fs)	ALOXE3	Pathogenic	criteria provided, single submitter
217300	NC_000017.11:g.8017296_8022594del	ALOXE3	Pathogenic	no assertion criteria provided
217301	NM_021628.3(ALOXE3):c.418C>T (p.Arg140Ter)	ALOXE3	Pathogenic	criteria provided, single submitter
279677	NM_021628.3(ALOXE3):c.1889C>T (p.Pro630Leu)	ALOXE3	Pathogenic	criteria provided, multiple submitters, no conflicts
3407	NM_021628.3(ALOXE3):c.1498G>T (p.Val500Phe)	ALOXE3	Pathogenic	no assertion criteria provided
3408	NM_021628.3(ALOXE3):c.700C>T (p.Arg234Ter)	ALOXE3	Pathogenic	criteria provided, multiple submitters, no conflicts
3409	NM_021628.3(ALOXE3):c.1186C>A (p.Arg396Ser)	ALOXE3	Pathogenic	no assertion criteria provided
39548	NM_021628.3(ALOXE3):c.842G>T (p.Gly281Val)	ALOXE3	Pathogenic	no assertion criteria provided
39550	NM_021628.3(ALOXE3):c.434G>A (p.Arg145His)	ALOXE3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39551	NM_021628.3(ALOXE3):c.1280T>C (p.Leu427Pro)	ALOXE3	Pathogenic	no assertion criteria provided
633811	NM_021628.3(ALOXE3):c.834C>A (p.Tyr278Ter)	ALOXE3	Pathogenic	criteria provided, multiple submitters, no conflicts
72354	NM_021628.3(ALOXE3):c.631C>T (p.Arg211Ter)	ALOXE3	Pathogenic	criteria provided, multiple submitters, no conflicts
973092	NM_021628.3(ALOXE3):c.1954C>T (p.Gln652Ter)	ALOXE3	Pathogenic	no assertion criteria provided
982895	NM_021628.3(ALOXE3):c.680+1G>A	ALOXE3	Pathogenic	criteria provided, multiple submitters, no conflicts
995448	NM_021628.3(ALOXE3):c.1193C>T (p.Ser398Phe)	ALOXE3	Pathogenic	no assertion criteria provided
995449	NM_021628.3(ALOXE3):c.758del (p.Phe253fs)	ALOXE3	Pathogenic	no assertion criteria provided
995450	NM_021628.3(ALOXE3):c.957G>A (p.Glu319=)	ALOXE3	Pathogenic	no assertion criteria provided
995451	NM_021628.3(ALOXE3):c.327C>A (p.Cys109Ter)	ALOXE3	Pathogenic	no assertion criteria provided
995452	NM_021628.3(ALOXE3):c.1803_1804dup (p.Met602fs)	ALOXE3	Pathogenic	no assertion criteria provided
995453	NM_021628.3(ALOXE3):c.1786-63_1807del	ALOXE3	Pathogenic	no assertion criteria provided
995454	NM_021628.3(ALOXE3):c.353-1G>C	ALOXE3	Pathogenic	no assertion criteria provided
995455	NM_021628.3(ALOXE3):c.1305+1_1305+2delinsTA	ALOXE3	Pathogenic	no assertion criteria provided
995456	NM_021628.3(ALOXE3):c.38_41del (p.Pro12_Tyr13insTer)	ALOXE3	Pathogenic	criteria provided, single submitter
995458	NM_021628.3(ALOXE3):c.57_63del (p.Asp20fs)	ALOXE3	Pathogenic	no assertion criteria provided
995460	NM_021628.3(ALOXE3):c.1812T>A (p.Asn604Lys)	ALOXE3	Pathogenic	no assertion criteria provided
995461	NM_021628.3(ALOXE3):c.271G>T (p.Glu91Ter)	ALOXE3	Pathogenic	no assertion criteria provided
995462	NM_021628.3(ALOXE3):c.1061G>A (p.Trp354Ter)	ALOXE3	Pathogenic	no assertion criteria provided
995463	NM_021628.3(ALOXE3):c.833A>G (p.Tyr278Cys)	ALOXE3	Pathogenic	no assertion criteria provided
995464	NM_021628.3(ALOXE3):c.1292dup (p.His431fs)	ALOXE3	Pathogenic	no assertion criteria provided
995465	NM_021628.3(ALOXE3):c.1031_1039del (p.Gln344_Ala347delinsPro)	ALOXE3	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ALOXE3	Definitive	Autosomal recessive	autosomal recessive congenital ichthyosis 3	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALOXE3	Orphanet:281122	Self-improving collodion baby
ALOXE3	Orphanet:313	Lamellar ichthyosis
ALOXE3	Orphanet:79394	Congenital ichthyosiform erythroderma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALOXE3	HGNC:13743	ENSG00000179148	Q9BYJ1	Hydroperoxide isomerase ALOXE3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALOXE3	Hydroperoxide isomerase ALOXE3	Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced lipoxygenases activity.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALOXE3	Enzyme (other)	yes	4.2.1.152	LipOase, PLAT/LH2_dom, LipOase_mml

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALOXE3	141	tissue_specific	yes	skin of leg, skin of abdomen, zone of skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALOXE3	1,129

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALOXE3	Q9BYJ1	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of 12-eicosatetraenoic acid derivatives	1	1631.4×	0.003	ALOXE3
Arachidonate metabolism	1	571.0×	0.004	ALOXE3
Fatty acid metabolism	1	131.3×	0.013	ALOXE3
Metabolism of lipids	1	31.6×	0.040	ALOXE3
Metabolism	1	11.6×	0.086	ALOXE3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
lipid oxidation	1	2106.5×	0.002	ALOXE3
hepoxilin biosynthetic process	1	2106.5×	0.002	ALOXE3
lipoxygenase pathway	1	1532.0×	0.002	ALOXE3
peroxisome proliferator activated receptor signaling pathway	1	1532.0×	0.002	ALOXE3
sphingolipid metabolic process	1	991.3×	0.002	ALOXE3
linoleic acid metabolic process	1	702.2×	0.003	ALOXE3
arachidonate metabolic process	1	481.5×	0.003	ALOXE3
establishment of skin barrier	1	455.5×	0.003	ALOXE3
ceramide biosynthetic process	1	421.3×	0.003	ALOXE3
sensory perception of pain	1	374.5×	0.003	ALOXE3
fat cell differentiation	1	181.2×	0.006	ALOXE3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALOXE3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALOXE3	4.2.1.152	hydroperoxy icosatetraenoate dehydratase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ALOXE3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ALOXE3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.