Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis

Summary

Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis (MONDO:0017992) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis
Mondo ID	MONDO:0017992
Orphanet	329173
UMLS	C5394674
MedGen	1720168
GARD	0017494
Is cancer (heuristic)	no

Data availability: 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorder of glycogen metabolism › autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis

Related subtypes (23): glycogen storage disease I, glycogen storage disease due to GLUT2 deficiency, glycogen storage disease II, glycogen storage disease III, glycogen storage disease due to glycogen branching enzyme deficiency, glycogen storage disease V, glycogen storage disease VI, glycogen storage disease VII, glycogen storage disorder due to hepatic glycogen synthase deficiency, Lafora disease, glycogen storage disease due to phosphoglycerate mutase deficiency, lethal congenital glycogen storage disease of heart, Danon disease, glycogen storage disease IXd, glycogen storage disease due to phosphoglycerate kinase 1 deficiency, glycogen storage disease due to muscle and heart glycogen synthase deficiency, glycogen storage disease due to muscle beta-enolase deficiency, glycogen storage disease due to lactate dehydrogenase M-subunit deficiency, polyglucosan body myopathy 1 with or without immunodeficiency, glycogen storage disease due to lactate dehydrogenase deficiency, glycogen storage disease due to liver phosphorylase kinase deficiency, GYG1-related disorder of glycogen metabolism, glycogen storage disease IX

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: 3 · 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
RBCK1	Supportive	Autosomal recessive	autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis	5
RNF31	Supportive	Autosomal recessive	autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RBCK1	Orphanet:329173	Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis
RBCK1	Orphanet:397937	Polyglucosan body myopathy type 1
RNF31	Orphanet:329173	Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis

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
RBCK1	HGNC:15864	ENSG00000125826	Q9BYM8	RanBP-type and C3HC4-type zinc finger-containing protein 1	gencc
RNF31	HGNC:16031	ENSG00000092098	Q96EP0	E3 ubiquitin-protein ligase RNF31	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RBCK1	RanBP-type and C3HC4-type zinc finger-containing protein 1	E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates.
RNF31	E3 ubiquitin-protein ligase RNF31	E3 ubiquitin-protein ligase component of the LUBAC complex which conjugates linear (‘Met-1’-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 0 · 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
Transcription factor	2	8.3×	0.015

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RBCK1	Transcription factor	no		Ubiquitin-like_dom, Znf_RING, Znf_RanBP2
RNF31	Transcription factor	no	2.3.2.31	Znf_RanBP2, IBR_dom, Znf_RING/FYVE/PHD

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
apex of heart	1
granulocyte	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RBCK1	279	ubiquitous	marker	right hemisphere of cerebellum, adenohypophysis, cerebellar hemisphere
RNF31	134	ubiquitous	yes	spleen, granulocyte, apex of heart

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RNF31	2,721
RBCK1	2,468

Intra-cohort edges

A	B	Sources
RBCK1	RNF31	intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RNF31	Q96EP0	36
RBCK1	Q9BYM8	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
TNFR1-induced proapoptotic signaling	2	439.2×	3e-05	RBCK1, RNF31
TNFR1-induced NF-kappa-B signaling pathway	2	335.9×	3e-05	RBCK1, RNF31
Regulation of TNFR1 signaling	2	223.9×	5e-05	RBCK1, RNF31
TNF signaling	1	211.5×	0.008	RNF31
Death Receptor Signaling	1	69.6×	0.020	RNF31
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.062	RBCK1
Signal Transduction	1	5.1×	0.187	RNF31

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
protein linear polyubiquitination	2	5617.3×	3e-07	RBCK1, RNF31
negative regulation of necroptotic process	2	991.3×	8e-06	RBCK1, RNF31
canonical NF-kappaB signal transduction	2	366.4×	4e-05	RBCK1, RNF31
obsolete positive regulation of NF-kappaB transcription factor activity	2	205.5×	9e-05	RBCK1, RNF31
negative regulation of canonical NF-kappaB signal transduction	2	172.0×	1e-04	RBCK1, RNF31
T cell receptor signaling pathway	2	151.8×	1e-04	RBCK1, RNF31
protein polyubiquitination	2	115.4×	2e-04	RBCK1, RNF31
defense response to bacterium	2	108.0×	2e-04	RBCK1, RNF31
positive regulation of canonical NF-kappaB signal transduction	2	72.6×	3e-04	RBCK1, RNF31
positive regulation of xenophagy	1	1053.2×	0.002	RNF31
CD40 signaling pathway	1	842.6×	0.002	RNF31
obsolete positive regulation of protein targeting to mitochondrion	1	247.8×	0.005	RNF31
positive regulation of extrinsic apoptotic signaling pathway	1	227.7×	0.005	RBCK1
obsolete negative regulation of NF-kappaB transcription factor activity	1	179.3×	0.006	RBCK1
positive regulation of non-canonical NF-kappaB signal transduction	1	127.7×	0.008	RBCK1
proteasome-mediated ubiquitin-dependent protein catabolic process	1	26.1×	0.038	RBCK1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RBCK1	0	0
RNF31	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
RNF31	2	Binding:2
RBCK1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RNF31	2.3.2.31	RBR-type E3 ubiquitin transferase

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

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	2	RBCK1, RNF31

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
RBCK1	1	—
RNF31	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.