Autosomal recessive congenital ichthyosis 11

Summary

Autosomal recessive congenital ichthyosis 11 (MONDO:0011218) is a disease caused by ST14 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ST14 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 14
• Phenotypes (HPO): 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		11	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

2 HPO clinical features (Orphanet curated; top 2 by frequency):

HPO ID	Term	Frequency
HP:0008064	Ichthyosis	Very frequent (80-99%)
HP:0008070	Sparse hair	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive congenital ichthyosis 11
Mondo ID	MONDO:0011218
MeSH	C536273
OMIM	602400
Orphanet	91132
DOID	DOID:0060720
UMLS	C1835851
MedGen	332073
GARD	0010116
Is cancer (heuristic)	no

Also known as: ARCI11 · ARIH · autosomal recessive congenital ichthyosis 11 · autosomal recessive congenital ichthyosis type 11 · hypotrichosis-congenital ichthyosis syndrome · ichthyosis and follicular atrophoderma with hypotrichosis and hypohidrosis · ichthyosis, congenital, autosomal recessive 11 · ichthyosis, congenital, autosomal recessive type 11 · ichthyosis-follicular atrophoderma-hypotrichosis syndrome · ichthyosis-follicular atrophoderma-hypotrichosis-hypohidrosis syndrome · ichthyosis-hypotrichosis syndrome · IFAH syndrome · IHS

Data availability: 14 ClinVar variants · 6 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 11

Related subtypes (12): autosomal recessive congenital ichthyosis 1, autosomal recessive congenital ichthyosis 4A, autosomal recessive congenital ichthyosis 5, 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

14 retrieved; paginated sample, class counts are floors:

6 benign, 4 pathogenic, 3 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
126420	NM_021978.4(ST14):c.2034del (p.Leu678fs)	ST14	Pathogenic	no assertion criteria provided
4038	NM_021978.4(ST14):c.2479G>A (p.Gly827Arg)	ST14	Pathogenic	no assertion criteria provided
4039	NM_021978.4(ST14):c.3G>A (p.Met1Ile)	ST14	Pathogenic	no assertion criteria provided
4081066	NM_021978.4(ST14):c.598+1G>A	ST14	Pathogenic	criteria provided, single submitter
126419	NM_021978.4(ST14):c.2269+1G>A	ST14	Likely pathogenic	criteria provided, single submitter
1325140	NM_021978.4(ST14):c.241+1G>A	ST14	Likely pathogenic	criteria provided, single submitter
979027	NM_021978.4(ST14):c.1315G>A (p.Gly439Ser)	ST14	Likely pathogenic	no assertion criteria provided
4080380	NM_021978.4(ST14):c.782G>A (p.Arg261His)	ST14	Uncertain significance	criteria provided, single submitter
1237410	NM_021978.4(ST14):c.1684+38C>T	ST14	Benign	criteria provided, multiple submitters, no conflicts
1266188	NM_021978.4(ST14):c.1015+40A>G	ST14	Benign	criteria provided, multiple submitters, no conflicts
1273229	NM_021978.4(ST14):c.875+23A>G	ST14	Benign	criteria provided, multiple submitters, no conflicts
1283428	NM_021978.4(ST14):c.1223+29G>A	ST14	Benign	criteria provided, multiple submitters, no conflicts
518237	NM_021978.4(ST14):c.1113+15G>A	ST14	Benign	criteria provided, multiple submitters, no conflicts
518238	NM_021978.4(ST14):c.1215C>T (p.Asn405=)	ST14	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 23 · Orphanet: 9 · 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
KRT1	Definitive	Autosomal dominant	annular epidermolytic ichthyosis	18
ST14	Strong	Autosomal recessive	autosomal recessive congenital ichthyosis 11	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ST14	Orphanet:91132	Ichthyosis-hypotrichosis syndrome
KRT1	Orphanet:2199	Epidermolytic palmoplantar keratoderma
KRT1	Orphanet:281139	Annular epidermolytic ichthyosis
KRT1	Orphanet:281190	Congenital reticular ichthyosiform erythroderma
KRT1	Orphanet:312	Autosomal dominant epidermolytic ichthyosis
KRT1	Orphanet:50942	Striate palmoplantar keratoderma
KRT1	Orphanet:530838	KRT1-related diffuse nonepidermolytic keratoderma
KRT1	Orphanet:538574	Palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome
KRT1	Orphanet:79503	Ichthyosis hystrix of Curth-Macklin

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ST14	HGNC:11344	ENSG00000149418	Q9Y5Y6	Suppressor of tumorigenicity 14 protein	gencc,clinvar
KRT1	HGNC:6412	ENSG00000167768	P04264	Keratin, type II cytoskeletal 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ST14	Suppressor of tumorigenicity 14 protein	Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site.
KRT1	Keratin, type II cytoskeletal 1	May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	18.3×	0.108
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ST14	Protease	yes	3.4.21.109	SEA_dom, CUB_dom, Trypsin_dom
KRT1	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
duodenum	1
mucosa of transverse colon	1
nasal cavity epithelium	1
mammalian vulva	1
skin of hip	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ST14	246	broad	marker	mucosa of transverse colon, nasal cavity epithelium, duodenum
KRT1	177	tissue_specific	marker	mammalian vulva, upper leg skin, skin of hip

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT1	2,716
ST14	1,383

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ST14	Q9Y5Y6	25
KRT1	P04264	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 evidence-associated genes (2 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 2 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	2	87.8×	0.001	ST14, KRT1
Keratinization	2	55.7×	0.002	ST14, KRT1
Regulation of FXIIa and plasma kallikrein activity	1	571.0×	0.006	KRT1
Developmental Biology	2	14.5×	0.012	ST14, KRT1
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	139.3×	0.014	KRT1
Developmental Cell Lineages	1	112.0×	0.015	KRT1
FXIIa activates plasma kallikrein-kinin system	1	86.5×	0.016	KRT1
Innate Immune System	1	12.8×	0.094	KRT1
Neutrophil degranulation	1	11.5×	0.094	KRT1
Immune System	1	6.5×	0.148	KRT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
epithelial cell morphogenesis involved in placental branching	1	2808.7×	0.005	ST14
complement activation, lectin pathway	1	842.6×	0.007	KRT1
protein heterotetramerization	1	526.6×	0.007	KRT1
cornification	1	526.6×	0.007	KRT1
fibrinolysis	1	421.3×	0.007	KRT1
establishment of skin barrier	1	227.7×	0.010	KRT1
regulation of angiogenesis	1	210.7×	0.010	KRT1
keratinocyte differentiation	1	123.9×	0.012	ST14
intermediate filament organization	1	120.4×	0.012	KRT1
protein catabolic process	1	118.7×	0.012	ST14
keratinization	1	117.0×	0.012	KRT1
neural tube closure	1	93.6×	0.013	ST14
negative regulation of inflammatory response	1	68.5×	0.016	KRT1
response to oxidative stress	1	65.3×	0.016	KRT1
proteolysis	1	17.1×	0.058	ST14

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ST14	RIVAROXABAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ST14	5	4
KRT1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIVAROXABAN	4	ST14
HEXAMIDINE	4	ST14
PENTAMIDINE	4	ST14
NAFAMOSTAT	3	ST14
DIBROMPROPAMIDINE	2	ST14

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ST14	96	Binding:91, ADMET:4, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ST14	3.4.21.109	matriptase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

5 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.

Compound	Max phase	Cohort target (bioactivity)
RIVAROXABAN	4	ST14
HEXAMIDINE	4	ST14
PENTAMIDINE	4	ST14
NAFAMOSTAT	3	ST14
DIBROMPROPAMIDINE	2	ST14

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ST14
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	KRT1

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)
KRT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.