Hereditary periodic fever syndrome

Summary

Hereditary periodic fever syndrome (MONDO:0017953) is a disease (an umbrella term covering 6 Mondo subtypes) with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include canakinumab.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 1
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary periodic fever syndrome
Mondo ID	MONDO:0017953
MeSH	D056660
Orphanet	324924
UMLS	C0751422
MedGen	199651
GARD	0021453
Is cancer (heuristic)	no

Also known as: hereditary periodic fever syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › autoinflammatory syndrome › periodic fever syndrome › hereditary periodic fever syndrome

Related subtypes (2): unexplained periodic fever syndrome, periodic fever syndrome of childhood

Subtypes (6): TNF receptor 1-associated periodic fever syndrome, periodic fever-infantile enterocolitis-autoinflammatory syndrome, autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive, cryopyrin-associated periodic syndrome, mevalonate kinase deficiency, familial Mediterranean fever

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

No tiered GWAS variants or ClinVar records for this disease.

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	Limited	Autosomal dominant	hereditary periodic fever syndrome	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

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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06838143	Not specified	RECRUITING	Ilaris NIS in Korea

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CANAKINUMAB	4	1