Autosomal recessive congenital ichthyosis 8

Summary

Autosomal recessive congenital ichthyosis 8 (MONDO:0013495) is a disease caused by LIPN (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LIPN (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive congenital ichthyosis 8
Mondo ID	MONDO:0013495
OMIM	613943
DOID	DOID:0060717
UMLS	C3553029
MedGen	765943
GARD	0016457
Is cancer (heuristic)	no

Also known as: ARCI8 · autosomal recessive congenital ichthyosis type 8 · ichthyosis, congenital, autosomal recessive 8 · ichthyosis, congenital, autosomal recessive type 8 · ichthyosis, lamellar, 4

Data availability: 4 ClinVar variants · 3 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 › autosomal recessive congenital ichthyosis 8

Related subtypes (12): autosomal recessive congenital ichthyosis 1, autosomal recessive congenital ichthyosis 4A, autosomal recessive congenital ichthyosis 11, autosomal recessive congenital ichthyosis 5, ichthyosis, congenital, autosomal recessive 12, bathing suit ichthyosis, self-healing collodion baby, acral self-healing collodion baby, exfoliative ichthyosis, congenital non-bullous ichthyosiform erythroderma, ichthyosis, congenital, autosomal recessive 14, ichthyosis, congenital, autosomal recessive 13

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

4 retrieved; paginated sample, class counts are floors:

2 benign, 1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
31088	NM_001102469.2(LIPN):c.399_400del (p.Glu133fs)	LIPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4079202	NM_001102469.2(LIPN):c.1154G>A (p.Arg385Gln)	LIPN	Uncertain significance	criteria provided, single submitter
1238700	NM_001102469.2(LIPN):c.297T>C (p.Ala99=)	LIPN	Benign	criteria provided, multiple submitters, no conflicts
1270910	NM_001102469.2(LIPN):c.731C>A (p.Thr244Asn)	LIPN	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
LIPN	Strong	Autosomal recessive	autosomal recessive congenital ichthyosis 8	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LIPN	Orphanet:313	Lamellar ichthyosis

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
LIPN	HGNC:23452	ENSG00000204020	Q5VXI9	Lipase member N	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LIPN	Lipase member N	Plays a highly specific role in the last step of keratinocyte differentiation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LIPN	Other/Unknown	no		AB_hydrolase_1, Lipase_euk, AB_hydrolase_fold

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
leukocyte	1
monocyte	1
skin of abdomen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LIPN	88	tissue_specific	yes	monocyte, leukocyte, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LIPN	1,288

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LIPN	Q5VXI9	92.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Formation of the cornified envelope	1	87.8×	0.027	LIPN
Keratinization	1	55.7×	0.027	LIPN
Developmental Biology	1	14.5×	0.069	LIPN

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
cornification	1	1053.2×	0.003	LIPN
lipid catabolic process	1	244.2×	0.006	LIPN
lipid metabolic process	1	91.6×	0.011	LIPN

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
LIPN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	LIPN

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)
LIPN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.