Ichthyosiform erythroderma, corneal involvement, and hearing loss

Summary

Ichthyosiform erythroderma, corneal involvement, and hearing loss (MONDO:0009440) is a disease caused by AP1B1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: AP1B1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ichthyosiform erythroderma, corneal involvement, and hearing loss
Mondo ID	MONDO:0009440
MeSH	C537363
OMIM	242150
SNOMED CT	403780007
UMLS	C1275089
MedGen	224809
GARD	0002946
Is cancer (heuristic)	no

Also known as: ichthyosiform erythroderma, corneal involvement, and deafness · ichthyosiform erythroderma, corneal involvement, deafness

Data availability: 15 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 › keratosis › palmoplantar keratosis › hereditary palmoplantar keratoderma › diffuse palmoplantar keratoderma › KID syndrome › ichthyosiform erythroderma, corneal involvement, and hearing loss

Related subtypes (2): autosomal dominant keratitis-ichthyosis-hearing loss syndrome, ichthyosis, hystrix-like, with hearing loss

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

15 retrieved; paginated sample, class counts are floors:

11 pathogenic, 2 benign, 1 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1048800	NM_001127.4(AP1B1):c.1263C>A (p.Tyr421Ter)	AP1B1	Pathogenic	no assertion criteria provided
1700245	NM_001127.4(AP1B1):c.322C>T (p.Arg108Trp)	AP1B1	Pathogenic	no assertion criteria provided
1700246	NM_001127.4(AP1B1):c.668T>C (p.Leu223Pro)	AP1B1	Pathogenic	no assertion criteria provided
1700247	NM_001127.4(AP1B1):c.1852C>T (p.Gln618Ter)	AP1B1	Pathogenic	no assertion criteria provided
1700248	NM_001127.4(AP1B1):c.2677C>T (p.Gln893Ter)	AP1B1	Pathogenic	no assertion criteria provided
4071487	NM_001127.4(AP1B1):c.667del (p.Leu223fs)	AP1B1	Pathogenic	no assertion criteria provided
805794	NC_000022.10:g.29758984_29815476del	AP1B1	Pathogenic	no assertion criteria provided
805795	NM_001127.4(AP1B1):c.38-1G>A	AP1B1	Pathogenic	no assertion criteria provided
805796	NM_001127.4(AP1B1):c.430T>C (p.Cys144Arg)	AP1B1	Pathogenic	no assertion criteria provided
805797	NM_001127.4(AP1B1):c.2335del (p.Leu779fs)	AP1B1	Pathogenic	no assertion criteria provided
805798	NM_001127.4(AP1B1):c.2374G>T (p.Glu792Ter)	AP1B1	Pathogenic	no assertion criteria provided
1339533	NM_001127.4(AP1B1):c.2T>C (p.Met1Thr)	AP1B1	Likely pathogenic	criteria provided, single submitter
3377560	NM_001127.4(AP1B1):c.528G>A (p.Val176=)	AP1B1	Uncertain significance	criteria provided, single submitter
1192401	NM_001127.4(AP1B1):c.2349G>A (p.Ala783=)	AP1B1	Benign	criteria provided, multiple submitters, no conflicts
1192402	NM_001127.4(AP1B1):c.204A>G (p.Leu68=)	AP1B1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
AP1B1	Definitive	Autosomal recessive	ichthyosiform erythroderma, corneal involvement, and hearing loss	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AP1B1	Orphanet:171851	MEDNIK syndrome

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
AP1B1	HGNC:554	ENSG00000100280	Q10567	AP-1 complex subunit beta-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AP1B1	AP-1 complex subunit beta-1	Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AP1B1	Antibody/Immunoglobulin	yes		Armadillo, Clathrin/coatomer_adapt-like_N, Clathrin_a/b/g-adaptin_app_Ig

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

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
endometrium epithelium	1
middle frontal gyrus	1
paraflocculus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AP1B1	286	ubiquitous	marker	endometrium epithelium, middle frontal gyrus, paraflocculus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AP1B1	510

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AP1B1	Q10567	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Nef mediated downregulation of MHC class I complex cell surface expression	1	1142.0×	0.008	AP1B1
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1	634.4×	0.008	AP1B1
The role of Nef in HIV-1 replication and disease pathogenesis	1	634.4×	0.008	AP1B1
Host Interactions of HIV factors	1	335.9×	0.010	AP1B1
Lysosome Vesicle Biogenesis	1	326.3×	0.010	AP1B1
trans-Golgi Network Vesicle Budding	1	253.8×	0.011	AP1B1
Golgi Associated Vesicle Biogenesis	1	200.3×	0.011	AP1B1
HIV Infection	1	119.0×	0.017	AP1B1
MHC class II antigen presentation	1	89.2×	0.020	AP1B1
Membrane Trafficking	1	37.1×	0.041	AP1B1
Vesicle-mediated transport	1	34.8×	0.041	AP1B1
Viral Infection Pathways	1	30.8×	0.041	AP1B1
Adaptive Immune System	1	29.8×	0.041	AP1B1
Infectious disease	1	24.8×	0.046	AP1B1
Disease	1	13.1×	0.077	AP1B1
Immune System	1	13.0×	0.077	AP1B1

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
basolateral protein secretion	1	3370.4×	0.002	AP1B1
melanosome assembly	1	887.0×	0.004	AP1B1
platelet dense granule organization	1	674.1×	0.004	AP1B1
determination of left/right symmetry	1	255.3×	0.008	AP1B1
kidney development	1	140.4×	0.011	AP1B1
vesicle-mediated transport	1	96.3×	0.014	AP1B1
heart development	1	78.8×	0.015	AP1B1
intracellular protein transport	1	64.8×	0.015	AP1B1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AP1B1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
AP1B1	1	Binding:1

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	AP1B1
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)
AP1B1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.