focal facial dermal dysplasia type IV

Summary

focal facial dermal dysplasia type IV (MONDO:0013997) is a disease caused by CYP26C1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CYP26C1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		21	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0004426	Abnormality of the cheek	Very frequent (80-99%)
HP:0008066	Abnormal blistering of the skin	Very frequent (80-99%)
HP:3000019	Abnormality of buccal mucosa	Very frequent (80-99%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000331	Short chin	Frequent (30-79%)
HP:0001028	Hemangioma	Frequent (30-79%)
HP:0001269	Hemiparesis	Frequent (30-79%)
HP:0002170	Intracranial hemorrhage	Frequent (30-79%)
HP:0003764	Nevus	Frequent (30-79%)
HP:0007359	Focal-onset seizure	Frequent (30-79%)
HP:0011124	Abnormality of epidermal morphology	Frequent (30-79%)
HP:0025167	Fragmented elastic fibers in the dermis	Frequent (30-79%)
HP:0100494	Abnormal mast cell morphology	Frequent (30-79%)
HP:0100699	Scarring	Frequent (30-79%)
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000204	Cleft upper lip	Frequent (30-79%)
HP:0000238	Hydrocephalus	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	focal facial dermal dysplasia type IV
Mondo ID	MONDO:0013997
OMIM	614974
Orphanet	398189
UMLS	C3554246
MedGen	767160
GARD	0017650
Is cancer (heuristic)	no

Also known as: FFDD type IV · FFDD4 · focal facial dermal dysplasia 4 · focal Facial dermal dysplasia type 4 · focal facial preauricular dysplasia

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › focal facial dermal dysplasia › focal facial dermal dysplasia type IV

Related subtypes (3): focal facial dermal dysplasia type I, focal facial dermal dysplasia type III, focal facial dermal dysplasia type II

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

6 retrieved; paginated sample, class counts are floors:

3 likely pathogenic, 2 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3065284	NM_183374.3(CYP26C1):c.1191+1G>A	CYP26C1	Likely pathogenic	criteria provided, single submitter
4685469	NM_183374.3(CYP26C1):c.1238_1260del (p.Asp413fs)	CYP26C1	Likely pathogenic	criteria provided, single submitter
4845661	NM_183374.3(CYP26C1):c.1056C>A (p.Cys352Ter)	CYP26C1	Likely pathogenic	criteria provided, single submitter
3025146	NM_183374.3(CYP26C1):c.862G>A (p.Glu288Lys)	CYP26C1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
496732	NM_183374.3(CYP26C1):c.845_851dup (p.Gln284fs)	CYP26C1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779212	NM_183374.3(CYP26C1):c.1133G>C (p.Arg378Pro)	CYP26C1	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
CYP26C1	Strong	Autosomal recessive	focal facial dermal dysplasia type IV	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYP26C1	Orphanet:398189	Focal facial dermal dysplasia type IV

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
CYP26C1	HGNC:20577	ENSG00000187553	Q6V0L0	Cytochrome P450 26C1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYP26C1	Cytochrome P450 26C1	A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals.

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)
CYP26C1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-IV, Cyt_P450_CS

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
prefrontal cortex	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYP26C1	15	tissue_specific	yes	primordial germ cell in gonad, colonic epithelium, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP26C1	1,200

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CYP26C1	Q6V0L0	89.34

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
Defective CYP26C1 causes FFDD4	1	11420.0×	3e-04	CYP26C1
Vitamins	1	1903.3×	8e-04	CYP26C1
RA biosynthesis pathway	1	475.8×	0.002	CYP26C1

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
organelle fusion	1	4213.0×	8e-04	CYP26C1
retinoic acid catabolic process	1	3370.4×	8e-04	CYP26C1
vitamin metabolic process	1	2808.7×	8e-04	CYP26C1
negative regulation of retinoic acid receptor signaling pathway	1	1532.0×	0.001	CYP26C1
neural crest cell development	1	802.5×	0.002	CYP26C1
anterior/posterior pattern specification	1	181.2×	0.006	CYP26C1
central nervous system development	1	115.4×	0.009	CYP26C1

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
CYP26C1	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	CYP26C1

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)
CYP26C1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.