Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant

Summary

Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant (MONDO:0700338) is a disease caused by OTULIN (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: OTULIN (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant
Mondo ID	MONDO:0700338
OMIM	621030
DOID	DOID:0061169
UMLS	C5975538
MedGen	1875068
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autoinflammation, panniculitis, and dermatosis syndrome › autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant

Related subtypes (1): autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3385324	C129S	OTULIN	Pathogenic	no assertion criteria provided
3385325	NM_138348.6(OTULIN):c.917G>A (p.Arg306Gln)	OTULIN	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
OTULIN	Definitive	Autosomal recessive	autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OTULIN	Orphanet:500062	Infantile-onset periodic fever-panniculitis-dermatosis 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
OTULIN	HGNC:25118	ENSG00000154124	Q96BN8	Ubiquitin thioesterase otulin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OTULIN	Ubiquitin thioesterase otulin	Deubiquitinase that specifically removes linear (‘Met-1’-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response.

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)
OTULIN	Other/Unknown	no		FAM105, Otulin

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
bone marrow cell	1
buccal mucosa cell	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OTULIN	234	ubiquitous	marker	buccal mucosa cell, bone marrow cell, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OTULIN	1,553

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OTULIN	Q96BN8	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	1	368.4×	0.004	OTULIN
Regulation of TNFR1 signaling	1	223.9×	0.004	OTULIN

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
protein linear deubiquitination	1	5617.3×	0.002	OTULIN
nucleotide-binding oligomerization domain containing 2 signaling pathway	1	1532.0×	0.004	OTULIN
regulation of tumor necrosis factor-mediated signaling pathway	1	702.2×	0.005	OTULIN
regulation of canonical Wnt signaling pathway	1	543.6×	0.005	OTULIN
sprouting angiogenesis	1	481.5×	0.005	OTULIN
obsolete negative regulation of NF-kappaB transcription factor activity	1	358.6×	0.005	OTULIN
negative regulation of inflammatory response	1	137.0×	0.011	OTULIN
Wnt signaling pathway	1	99.7×	0.014	OTULIN
protein ubiquitination	1	41.4×	0.030	OTULIN
proteolysis	1	34.2×	0.030	OTULIN
innate immune response	1	33.6×	0.030	OTULIN

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
OTULIN	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	OTULIN

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)
OTULIN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.