Autosomal recessive congenital ichthyosis 5

Summary

Autosomal recessive congenital ichthyosis 5 (MONDO:0011485) is a disease caused by CYP4F22 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CYP4F22 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 123

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive congenital ichthyosis 5
Mondo ID	MONDO:0011485
MeSH	C537265
OMIM	604777
DOID	DOID:0060714
UMLS	C1858133
MedGen	347628
GARD	0009734
Is cancer (heuristic)	no

Also known as: ARCI5 · autosomal recessive congenital ichthyosis 5 · autosomal recessive congenital ichthyosis type 5 · ichthyosis congenita 3 · ichthyosis congenita III · ichthyosis lamellar 3 · ichthyosis, congenital, autosomal recessive 5 · ichthyosis, congenital, autosomal recessive type 5 · ichthyosis, lamellar, 3 · ichthyosis, lamellar, 3, formerly · ichthyosis, NONLAMELLAR and NONERYTHRODERMIC, congenital, autosomal recessive · lamellar ichthyosis, type 3 · LI3, formerly · NNCI · type 3 lamellar ichthyosis

Data availability: 123 ClinVar variants · 2 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 5

Related subtypes (12): autosomal recessive congenital ichthyosis 1, autosomal recessive congenital ichthyosis 4A, autosomal recessive congenital ichthyosis 11, autosomal recessive congenital ichthyosis 8, 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

123 retrieved; paginated sample, class counts are floors:

40 uncertain significance, 32 pathogenic, 15 conflicting classifications of pathogenicity, 15 benign, 10 likely pathogenic, 4 likely benign, 4 pathogenic/likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1526150	NM_173483.4(CYP4F22):c.296G>A (p.Trp99Ter)	CYP4F22	Pathogenic	criteria provided, multiple submitters, no conflicts
279799	NM_173483.4(CYP4F22):c.59dup (p.Ile21fs)	CYP4F22	Pathogenic	criteria provided, multiple submitters, no conflicts
328433	NM_173483.4(CYP4F22):c.667C>T (p.Gln223Ter)	CYP4F22	Pathogenic	criteria provided, single submitter
379536	NM_173483.4(CYP4F22):c.1084C>T (p.Arg362Ter)	CYP4F22	Pathogenic	criteria provided, multiple submitters, no conflicts
420584	NM_173483.4(CYP4F22):c.976C>T (p.Arg326Ter)	CYP4F22	Pathogenic	criteria provided, multiple submitters, no conflicts
560306	NM_173483.4(CYP4F22):c.242G>A (p.Gly81Asp)	CYP4F22	Pathogenic	criteria provided, single submitter
560307	NM_173483.4(CYP4F22):c.493_499delinsCTTGATT (p.Phe165_Ile167delinsLeuAspPhe)	CYP4F22	Pathogenic	no assertion criteria provided
560308	NM_173483.4(CYP4F22):c.550-2A>T	CYP4F22	Pathogenic	no assertion criteria provided
560309	NM_173483.4(CYP4F22):c.592G>T (p.Asp198Tyr)	CYP4F22	Pathogenic	no assertion criteria provided
560310	NM_173483.4(CYP4F22):c.643_644del (p.Val215fs)	CYP4F22	Pathogenic	no assertion criteria provided
560311	NM_173483.4(CYP4F22):c.847C>T (p.Arg283Trp)	CYP4F22	Pathogenic	no assertion criteria provided
560312	NM_173483.4(CYP4F22):c.917T>C (p.Ile306Thr)	CYP4F22	Pathogenic	no assertion criteria provided
560315	NM_173483.4(CYP4F22):c.1532A>G (p.Glu511Gly)	CYP4F22	Pathogenic	no assertion criteria provided
560316	NM_173483.4(CYP4F22):c.720_723del (p.Val241fs)	CYP4F22	Pathogenic	criteria provided, single submitter
560317	NM_173483.4(CYP4F22):c.1352G>C (p.Arg451Pro)	CYP4F22	Pathogenic	no assertion criteria provided
560319	NM_173483.4(CYP4F22):c.421+1G>A	CYP4F22	Pathogenic	no assertion criteria provided
560320	NM_173483.4(CYP4F22):c.467G>A (p.Arg156His)	CYP4F22	Pathogenic	no assertion criteria provided
560321	NM_173483.4(CYP4F22):c.697A>C (p.Ile233Leu)	CYP4F22	Pathogenic	no assertion criteria provided
560322	NM_173483.4(CYP4F22):c.1163C>A (p.Thr388Lys)	CYP4F22	Pathogenic	no assertion criteria provided
560324	NM_173483.4(CYP4F22):c.1137-18_1137-4del	CYP4F22	Pathogenic	no assertion criteria provided
560325	NM_173483.4(CYP4F22):c.1084C>G (p.Arg362Gly)	CYP4F22	Pathogenic	no assertion criteria provided
560326	NM_173483.4(CYP4F22):c.177C>G (p.Phe59Leu)	CYP4F22	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
560327	NM_173483.4(CYP4F22):c.981del (p.Glu328fs)	CYP4F22	Pathogenic	no assertion criteria provided
560330	NM_173483.4(CYP4F22):c.727C>T (p.Arg243Cys)	CYP4F22	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
560331	NM_173483.4(CYP4F22):c.466C>T (p.Arg156Cys)	CYP4F22	Pathogenic	criteria provided, multiple submitters, no conflicts
560332	NM_173483.4(CYP4F22):c.1563G>A (p.Trp521Ter)	CYP4F22	Pathogenic	no assertion criteria provided
560333	NM_173483.4(CYP4F22):c.429dup (p.Leu144fs)	CYP4F22	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
560334	NM_173483.4(CYP4F22):c.844C>T (p.Arg282Trp)	CYP4F22	Pathogenic	criteria provided, single submitter
560336	NM_173483.4(CYP4F22):c.367+1G>A	CYP4F22	Pathogenic	no assertion criteria provided
560337	NM_173483.4(CYP4F22):c.1085G>A (p.Arg362Gln)	CYP4F22	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

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
CYP4F22	Strong	Autosomal recessive	autosomal recessive congenital ichthyosis 5	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYP4F22	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
CYP4F22	HGNC:26820	ENSG00000171954	Q6NT55	Ultra-long-chain fatty acid omega-hydroxylase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYP4F22	Ultra-long-chain fatty acid omega-hydroxylase	A cytochrome P450 monooxygenase involved in epidermal ceramide biosynthesis.

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)
CYP4F22	Enzyme (other)	yes	1.14.14.177	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS

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
lower esophagus mucosa	1
skin of leg	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYP4F22	103	tissue_specific	marker	lower esophagus mucosa, upper arm skin, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP4F22	1,462

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CYP4F22	Q6NT55	93.59

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
Defective CYP4F22 causes ARCI5	1	11420.0×	4e-04	CYP4F22
Miscellaneous substrates	1	951.7×	0.002	CYP4F22
Eicosanoids	1	951.7×	0.002	CYP4F22
Fatty acids	1	713.8×	0.002	CYP4F22
Synthesis of Leukotrienes (LT) and Eoxins (EX)	1	571.0×	0.002	CYP4F22

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
icosanoid metabolic process	1	1872.4×	0.001	CYP4F22
ceramide biosynthetic process	1	421.3×	0.002	CYP4F22

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
CYP4F22	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CYP4F22	1.14.14.177	ultra-long-chain fatty acid omega-hydroxylase

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	CYP4F22
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)
CYP4F22	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.