autoinflammatory syndrome, familial, Behcet-like 1

Summary

autoinflammatory syndrome, familial, Behcet-like 1 (MONDO:0800045) is a disease caused by TNFAIP3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TNFAIP3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 69

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autoinflammatory syndrome, familial, Behcet-like 1
Mondo ID	MONDO:0800045
OMIM	616744
Orphanet	476102, 674762
DOID	DOID:0080944
UMLS	C4225218
MedGen	898541
GARD	0017848
Is cancer (heuristic)	no

Also known as: AISBL · autoinflammatory syndrome, familial, Behcet-like · autoinflammatory syndrome, familial, Behcet-like 1 · Behçet-like disease due to HA20 · Behçet-like disease due to haploinsufficiency of A20 · hereditary paediatric Behçet-like disease · hereditary pediatric Behçet-like disease

Data availability: 69 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › autoinflammatory syndrome › autoinflammatory syndrome, familial, Behcet-like › autoinflammatory syndrome, familial, Behcet-like 1

Related subtypes (1): autoinflammatory syndrome, familial, X-linked, Behcet-like 2

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

69 retrieved; paginated sample, class counts are floors:

25 uncertain significance, 14 pathogenic, 7 conflicting classifications of pathogenicity, 7 benign/likely benign, 7 likely pathogenic, 4 likely benign, 3 benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1428578	NM_001270508.2(TNFAIP3):c.547C>T (p.Arg183Ter)	LOC126859807	Pathogenic	criteria provided, multiple submitters, no conflicts
219108	NM_001270508.2(TNFAIP3):c.680T>A (p.Leu227Ter)	LOC126859807	Pathogenic	no assertion criteria provided
219109	NM_001270508.2(TNFAIP3):c.671del (p.Phe224fs)	LOC126859807	Pathogenic	no assertion criteria provided
219113	NM_001270508.2(TNFAIP3):c.801del (p.Pro268fs)	LOC126859807	Pathogenic	no assertion criteria provided
1325206	NM_001270508.2(TNFAIP3):c.1477_1502del (p.Gly493fs)	TNFAIP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1676287	NM_001270508.2(TNFAIP3):c.1346del (p.Asn449fs)	TNFAIP3	Pathogenic	no assertion criteria provided
1676288	NM_001270508.2(TNFAIP3):c.1428G>A (p.Met476Ile)	TNFAIP3	Pathogenic	no assertion criteria provided
1723128	NM_001270508.2(TNFAIP3):c.1694C>G (p.Ser565Ter)	TNFAIP3	Pathogenic	criteria provided, single submitter
2036768	NM_001270508.2(TNFAIP3):c.948del (p.Trp317fs)	TNFAIP3	Pathogenic	criteria provided, single submitter
219110	NM_001270508.2(TNFAIP3):c.811C>T (p.Arg271Ter)	TNFAIP3	Pathogenic	criteria provided, multiple submitters, no conflicts
219112	NM_001270508.2(TNFAIP3):c.918C>G (p.Tyr306Ter)	TNFAIP3	Pathogenic	no assertion criteria provided
2500101	NM_001270508.2(TNFAIP3):c.1096G>T (p.Glu366Ter)	TNFAIP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3257891	NM_001270508.2(TNFAIP3):c.1777C>T (p.Gln593Ter)	TNFAIP3	Pathogenic	criteria provided, single submitter
3341072	NM_001270508.2(TNFAIP3):c.2185dup (p.Ser729fs)	TNFAIP3	Pathogenic	criteria provided, single submitter
3718613	NM_001270508.2(TNFAIP3):c.259C>T (p.Arg87Ter)	TNFAIP3	Pathogenic	criteria provided, multiple submitters, no conflicts
836614	NM_001270508.2(TNFAIP3):c.912del (p.Glu305fs)	TNFAIP3	Pathogenic	criteria provided, single submitter
1705586	NM_001270508.2(TNFAIP3):c.738C>G (p.Tyr246Ter)	LOC126859807	Likely pathogenic	criteria provided, single submitter
3893196	NM_001270508.2(TNFAIP3):c.653del (p.Leu218fs)	LOC126859807	Likely pathogenic	no assertion criteria provided
3900729	NM_001270508.2(TNFAIP3):c.635-2A>C	LOC126859807	Likely pathogenic	criteria provided, single submitter
2577872	NM_001270508.2(TNFAIP3):c.425G>A (p.Trp142Ter)	TNFAIP3	Likely pathogenic	criteria provided, single submitter
3376341	NM_001270508.2(TNFAIP3):c.505_544del (p.Asp169fs)	TNFAIP3	Likely pathogenic	criteria provided, single submitter
3906989	NM_001270508.2(TNFAIP3):c.1774_1795dup (p.Gly599fs)	TNFAIP3	Likely pathogenic	criteria provided, single submitter
4820168	NM_001270508.2(TNFAIP3):c.353_354del (p.Thr118fs)	TNFAIP3	Likely pathogenic	criteria provided, single submitter
1096311	NM_001270508.2(TNFAIP3):c.2364G>A (p.Met788Ile)	TNFAIP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135332	NM_001270508.2(TNFAIP3):c.374C>T (p.Ala125Val)	TNFAIP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135337	NM_001270508.2(TNFAIP3):c.839G>A (p.Arg280Gln)	TNFAIP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135345	NM_001270508.2(TNFAIP3):c.1939A>C (p.Thr647Pro)	TNFAIP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135348	NM_001270508.2(TNFAIP3):c.2231G>A (p.Gly744Asp)	TNFAIP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1429254	NM_001270508.2(TNFAIP3):c.2282G>A (p.Arg761His)	TNFAIP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
994419	NM_001270508.2(TNFAIP3):c.1809G>T (p.Gly603=)	TNFAIP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
TNFAIP3	Strong	Autosomal dominant	autoinflammatory syndrome, familial, Behcet-like 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNFAIP3	Orphanet:536	Systemic lupus erythematosus
TNFAIP3	Orphanet:674762	Early-onset autoinflammatory syndrome due to A20 haploinsufficiency

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
TNFAIP3	HGNC:11896	ENSG00000118503	P21580	Tumor necrosis factor alpha-induced protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNFAIP3	Tumor necrosis factor alpha-induced protein 3	Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNFAIP3	Transcription factor	no		Znf_A20, OTU_dom, OTU_Deubiquitinase

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
mucosa of paranasal sinus	1
vena cava	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNFAIP3	274	ubiquitous	marker	vena cava, mucosa of paranasal sinus, vermiform appendix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNFAIP3	3,716

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNFAIP3	P21580	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
TNFR1-induced proapoptotic signaling	1	439.2×	0.004	TNFAIP3
TNFR1-induced NF-kappa-B signaling pathway	1	335.9×	0.004	TNFAIP3
Negative regulators of DDX58/IFIH1 signaling	1	326.3×	0.004	TNFAIP3
NOD1/2 Signaling Pathway	1	317.2×	0.004	TNFAIP3
Ovarian tumor domain proteases	1	278.5×	0.004	TNFAIP3
Regulation of TNFR1 signaling	1	223.9×	0.004	TNFAIP3

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
negative regulation of toll-like receptor 5 signaling pathway	1	16852.0×	7e-04	TNFAIP3
regulation of vascular wound healing	1	16852.0×	7e-04	TNFAIP3
negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway	1	16852.0×	7e-04	TNFAIP3
establishment of protein localization to vacuole	1	16852.0×	7e-04	TNFAIP3
negative regulation of CD40 signaling pathway	1	8426.0×	0.001	TNFAIP3
negative regulation of chronic inflammatory response	1	5617.3×	0.001	TNFAIP3
tolerance induction to lipopolysaccharide	1	5617.3×	0.001	TNFAIP3
negative regulation of osteoclast proliferation	1	5617.3×	0.001	TNFAIP3
B-1 B cell homeostasis	1	4213.0×	0.001	TNFAIP3
negative regulation of toll-like receptor 3 signaling pathway	1	4213.0×	0.001	TNFAIP3
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	1	4213.0×	0.001	TNFAIP3
regulation of germinal center formation	1	2808.7×	0.001	TNFAIP3
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	1	2808.7×	0.001	TNFAIP3
negative regulation of toll-like receptor 2 signaling pathway	1	2407.4×	0.001	TNFAIP3
negative regulation of B cell activation	1	2407.4×	0.001	TNFAIP3
response to molecule of bacterial origin	1	2106.5×	0.001	TNFAIP3
regulation of defense response to virus by host	1	2106.5×	0.001	TNFAIP3
positive regulation of hepatocyte proliferation	1	1685.2×	0.002	TNFAIP3
protein K11-linked deubiquitination	1	1532.0×	0.002	TNFAIP3
response to muramyl dipeptide	1	1404.3×	0.002	TNFAIP3
protein deubiquitination involved in ubiquitin-dependent protein catabolic process	1	1296.3×	0.002	TNFAIP3
negative regulation of toll-like receptor 4 signaling pathway	1	1123.5×	0.002	TNFAIP3
negative regulation of bone resorption	1	991.3×	0.002	TNFAIP3
regulation of tumor necrosis factor-mediated signaling pathway	1	702.2×	0.003	TNFAIP3
protein K48-linked deubiquitination	1	648.1×	0.003	TNFAIP3
negative regulation of smooth muscle cell proliferation	1	624.1×	0.003	TNFAIP3
protein K63-linked deubiquitination	1	624.1×	0.003	TNFAIP3
negative regulation of interleukin-2 production	1	581.1×	0.003	TNFAIP3
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	581.1×	0.003	TNFAIP3
negative regulation of interleukin-1 beta production	1	510.7×	0.003	TNFAIP3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
TNFAIP3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TNFAIP3	1	Binding:1

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	TNFAIP3

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)
TNFAIP3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.