Sebocystomatosis

Summary

Sebocystomatosis (MONDO:0008485) is a disease caused by KRT17 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: KRT17 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 11
• Phenotypes (HPO): 3

Clinical features

Signs & symptoms

Clinical features (HPO)

3 HPO clinical features (Orphanet curated; top 3 by frequency):

HPO ID	Term	Frequency
HP:0009720	Adenoma sebaceum	Very frequent (80-99%)
HP:0012035	Steatocystoma multiplex	Very frequent (80-99%)
HP:0000787	Nephrolithiasis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	sebocystomatosis
Mondo ID	MONDO:0008485
OMIM	184500
Orphanet	841
DOID	DOID:0111556
ICD-10-CM	L72.2
SNOMED CT	109433009
UMLS	C0259771
MedGen	75476
GARD	0005003
Is cancer (heuristic)	no

Also known as: multiple sebaceous cysts · multiplex steatocystoma · Steatocystoma multiplex

Data availability: 11 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › sebaceous gland disorder › sebocystomatosis

Related subtypes (6): internal hordeolum, alopecia mucinosa, sebaceous gland neoplasm, acne, demodicidosis of sebaceous gland, rhinophyma

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

11 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
14587	NM_000422.3(KRT17):c.275A>G (p.Asn92Ser)	KRT17	Pathogenic	criteria provided, multiple submitters, no conflicts
14589	NM_000422.3(KRT17):c.274A>C (p.Asn92His)	KRT17	Pathogenic	no assertion criteria provided
14590	NM_000422.3(KRT17):c.281G>A (p.Arg94His)	KRT17	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14591	NM_000422.3(KRT17):c.280C>T (p.Arg94Cys)	KRT17	Pathogenic	criteria provided, multiple submitters, no conflicts
265321	NM_000422.3(KRT17):c.287CCT[1] (p.Ser97del)	KRT17	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
794186	NM_000422.3(KRT17):c.784A>T (p.Lys262Ter)	KRT17	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3393231	NM_000422.3(KRT17):c.538C>A (p.Arg180Ser)	KRT17	Uncertain significance	criteria provided, single submitter
3891521	NM_000422.3(KRT17):c.1153C>T (p.Arg385Cys)	KRT17	Uncertain significance	criteria provided, single submitter
3891522	NM_000422.3(KRT17):c.902C>T (p.Ser301Leu)	KRT17	Uncertain significance	criteria provided, single submitter
4278037	NM_000422.3(KRT17):c.77G>C (p.Arg26Pro)	KRT17	Uncertain significance	criteria provided, single submitter
773316	NM_000422.3(KRT17):c.834+5G>A	KRT17	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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
KRT17	Definitive	Autosomal dominant	sebocystomatosis	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KRT17	Orphanet:2309	Pachyonychia congenita
KRT17	Orphanet:841	Sebocystomatosis

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
KRT17	HGNC:6427	ENSG00000128422	Q04695	Keratin, type I cytoskeletal 17	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KRT17	Keratin, type I cytoskeletal 17	Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair.

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)
KRT17	Other/Unknown	no		Keratin_I, IF_conserved, IF_rod_dom

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
gingiva	1
gingival epithelium	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRT17	224	broad	marker	gingival epithelium, gingiva, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT17	2,523

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KRT17	Q04695	79.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.018	KRT17
Formation of the cornified envelope	1	87.8×	0.023	KRT17
Keratinization	1	55.7×	0.024	KRT17
Developmental Biology	1	14.5×	0.069	KRT17

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
positive regulation of hair follicle development	1	2407.4×	0.003	KRT17
hair follicle morphogenesis	1	495.6×	0.006	KRT17
morphogenesis of an epithelium	1	343.9×	0.006	KRT17
intermediate filament organization	1	240.7×	0.006	KRT17
keratinization	1	234.1×	0.006	KRT17
positive regulation of translation	1	227.7×	0.006	KRT17
positive regulation of cell growth	1	183.2×	0.006	KRT17
epithelial cell differentiation	1	175.5×	0.006	KRT17

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
KRT17	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	KRT17

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)
KRT17	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.