Ichthyosis, lamellar, autosomal dominant

Summary

Ichthyosis, lamellar, autosomal dominant (MONDO:0007812) is a disease caused by ASPRV1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ASPRV1 (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	ichthyosis, lamellar, autosomal dominant
Mondo ID	MONDO:0007812
MeSH	C537263
OMIM	146750
SNOMED CT	254164007
UMLS	C0432304
MedGen	98486
GARD	0009735
Is cancer (heuristic)	no

Also known as: ichthyosis lamellar, autosomal dominant · ichthyosis, lamellar, autosomal dominant

Data availability: 4 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › lamellar ichthyosis › ichthyosis, lamellar, autosomal dominant

Related subtypes (5): autosomal recessive congenital ichthyosis 4A, autosomal recessive congenital ichthyosis 5, autosomal recessive congenital ichthyosis 3, autosomal recessive congenital ichthyosis 6, autosomal recessive congenital ichthyosis 8

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:

3 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
977277	NM_152792.4(ASPRV1):c.343A>G (p.Lys115Glu)	ASPRV1	Pathogenic	no assertion criteria provided
977278	NM_152792.4(ASPRV1):c.688C>A (p.Pro230Thr)	ASPRV1	Pathogenic	no assertion criteria provided
977279	NM_152792.4(ASPRV1):c.680G>C (p.Arg227Pro)	ASPRV1	Pathogenic	no assertion criteria provided
3780822	NM_152792.4(ASPRV1):c.-153G>A	ASPRV1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
ASPRV1	Strong	Autosomal dominant	ichthyosis, lamellar, autosomal dominant	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ASPRV1	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
ASPRV1	HGNC:26321	ENSG00000244617	Q53RT3	Retroviral-like aspartic protease 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ASPRV1	Retroviral-like aspartic protease 1	Protease responsible for filaggrin processing, essential for the maintenance of a proper epidermis organization.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ASPRV1	Protease	yes		Aspartic_peptidase_AS, Peptidase_A2_cat, Peptidase_aspartic_dom_sf

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
nipple	1
upper arm skin	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ASPRV1	183	tissue_specific	yes	upper arm skin, upper leg skin, nipple

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ASPRV1	458

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ASPRV1	Q53RT3	70.77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
skin development	1	443.5×	0.005	ASPRV1
protein processing	1	170.2×	0.006	ASPRV1

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
ASPRV1	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	1	ASPRV1
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)
ASPRV1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.