autoinflammatory syndrome, familial, Behcet-like

Summary

autoinflammatory syndrome, familial, Behcet-like (MONDO:0031384) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autoinflammatory syndrome, familial, Behcet-like
Mondo ID	MONDO:0031384
OMIM	616744
GARD	0025698
Is cancer (heuristic)	no

Data availability: 22 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Related subtypes (36): cherubism, chronic recurrent multifocal osteomyelitis, Pelger-Huet-like anomaly and episodic fever with abdominal pain, pyogenic arthritis-pyoderma gangrenosum-acne syndrome, psoriasis 14, pustular, autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation, periodic fever syndrome, infantile onset panniculitis with uveitis and systemic granulomatosis, idiopathic recurrent pericarditis, pyoderma gangrenosum-acne-suppurative hidradenitis syndrome, neonatal inflammatory skin and bowel disease, magic syndrome, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, Schnitzler syndrome, PFAPA syndrome, pyoderma gangrenosum, SAPHO syndrome, sarcoidosis, adult-onset Still disease, systemic-onset juvenile idiopathic arthritis, VEXAS syndrome, CEBPE-associated autoinflammation-immunodeficiency-neutrophil dysfunction syndrome, type 1 interferonopathy, autoinflammatory disease, X-linked, autoinflammatory syndrome with immunodeficiency, early-onset pulmonary and cutaneous vasculitis, autoinflammatory syndrome due to TBK1 deficiency, F12-associated cold autoinflammatory syndrome, neonatal-onset severe multisystemic autoinflammatory disease with increased IL18, SAMD9L-associated autoinflammatory syndrome, autoinflammatory syndrome of childhood, autoinflammatory disease, systemic, with vasculitis, granulomatous autoinflammatory syndrome of childhood, autoinflammatory disease, multisystem, with immune dysregulation, X-linked, PAPASH syndrome, Sharpin-related autoinflammatory syndrome

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

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

22 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1684644	Single allele	ABRACL	Pathogenic	criteria provided, single submitter
1319978	NM_001270508.2(TNFAIP3):c.1727dup (p.His577fs)	TNFAIP3	Pathogenic	criteria provided, single submitter
2066370	NM_001270508.2(TNFAIP3):c.950G>A (p.Trp317Ter)	TNFAIP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
694368	GRCh37/hg19 6q23.3(chr6:138065475-138252638)x1	TNFAIP3	Pathogenic	no assertion criteria provided
998175	Single allele	TNFAIP3	Pathogenic	no assertion criteria provided
1028499	NM_001270508.2(TNFAIP3):c.22C>T (p.Gln8Ter)	TNFAIP3	Likely pathogenic	criteria provided, single submitter
1683561	NM_001270508.2(TNFAIP3):c.1035C>A (p.Tyr345Ter)	TNFAIP3	Likely pathogenic	criteria provided, single submitter
1113112	NM_001270508.2(TNFAIP3):c.2090G>A (p.Arg697Lys)	TNFAIP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135336	NM_001270508.2(TNFAIP3):c.742A>G (p.Ile248Val)	TNFAIP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135338	NM_001270508.2(TNFAIP3):c.1634C>T (p.Ala545Val)	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
1031619	NM_001270508.2(TNFAIP3):c.227C>T (p.Thr76Ile)	TNFAIP3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1331012	NM_001270508.2(TNFAIP3):c.1294G>A (p.Gly432Ser)	TNFAIP3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1675138	NM_001270508.2(TNFAIP3):c.1757C>T (p.Ala586Val)	TNFAIP3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679469	NM_001270508.2(TNFAIP3):c.980C>T (p.Ala327Val)	TNFAIP3	Uncertain significance	criteria provided, multiple submitters, no conflicts
812026	NM_001270508.2(TNFAIP3):c.1306G>A (p.Gly436Arg)	TNFAIP3	Uncertain significance	criteria provided, multiple submitters, no conflicts
973679	NM_001270508.2(TNFAIP3):c.1555G>A (p.Gly519Arg)	TNFAIP3	Uncertain significance	no assertion criteria provided
994249	NM_001270508.2(TNFAIP3):c.1828G>A (p.Ala610Thr)	TNFAIP3	Uncertain significance	criteria provided, multiple submitters, no conflicts
995597	NM_001270508.2(TNFAIP3):c.881C>T (p.Pro294Leu)	TNFAIP3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1281403	NM_001270508.2(TNFAIP3):c.805+28A>C	LOC126859807	Benign	criteria provided, multiple submitters, no conflicts
1330533	NM_001270508.2(TNFAIP3):c.1710C>T (p.Leu570=)	TNFAIP3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
993326	NM_001270508.2(TNFAIP3):c.296-15_296-13del	TNFAIP3	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TNFAIP3	HGNC:11896	ENSG00000118503	P21580	Tumor necrosis factor alpha-induced protein 3	clinvar
ABRACL	HGNC:21230	ENSG00000146386	Q9P1F3	Costars family protein ABRACL	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: 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNFAIP3	Transcription factor	no		Znf_A20, OTU_dom, OTU_Deubiquitinase
ABRACL	Other/Unknown	no		Costars_dom, Costars_sf, Costars

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
mucosa of paranasal sinus	1
vena cava	1
vermiform appendix	1
leukocyte	1
monocyte	1
mucosa of transverse colon	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
ABRACL	242	ubiquitous	marker	monocyte, leukocyte, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNFAIP3	3,716
ABRACL	635

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNFAIP3	P21580	17
ABRACL	Q9P1F3	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 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 2 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	8426.0×	0.001	TNFAIP3
regulation of vascular wound healing	1	8426.0×	0.001	TNFAIP3
negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway	1	8426.0×	0.001	TNFAIP3
establishment of protein localization to vacuole	1	8426.0×	0.001	TNFAIP3
negative regulation of CD40 signaling pathway	1	4213.0×	0.002	TNFAIP3
negative regulation of chronic inflammatory response	1	2808.7×	0.002	TNFAIP3
regulation of actin filament-based process	1	2808.7×	0.002	ABRACL
tolerance induction to lipopolysaccharide	1	2808.7×	0.002	TNFAIP3
negative regulation of osteoclast proliferation	1	2808.7×	0.002	TNFAIP3
B-1 B cell homeostasis	1	2106.5×	0.002	TNFAIP3
negative regulation of toll-like receptor 3 signaling pathway	1	2106.5×	0.002	TNFAIP3
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	1	2106.5×	0.002	TNFAIP3
regulation of germinal center formation	1	1404.3×	0.002	TNFAIP3
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	1	1404.3×	0.002	TNFAIP3
negative regulation of toll-like receptor 2 signaling pathway	1	1203.7×	0.002	TNFAIP3
negative regulation of B cell activation	1	1203.7×	0.002	TNFAIP3
response to molecule of bacterial origin	1	1053.2×	0.003	TNFAIP3
regulation of defense response to virus by host	1	1053.2×	0.003	TNFAIP3
positive regulation of hepatocyte proliferation	1	842.6×	0.003	TNFAIP3
protein K11-linked deubiquitination	1	766.0×	0.003	TNFAIP3
response to muramyl dipeptide	1	702.2×	0.003	TNFAIP3
protein deubiquitination involved in ubiquitin-dependent protein catabolic process	1	648.1×	0.003	TNFAIP3
negative regulation of toll-like receptor 4 signaling pathway	1	561.7×	0.004	TNFAIP3
negative regulation of bone resorption	1	495.6×	0.004	TNFAIP3
regulation of tumor necrosis factor-mediated signaling pathway	1	351.1×	0.005	TNFAIP3
protein K48-linked deubiquitination	1	324.1×	0.005	TNFAIP3
negative regulation of smooth muscle cell proliferation	1	312.1×	0.005	TNFAIP3
protein K63-linked deubiquitination	1	312.1×	0.005	TNFAIP3
negative regulation of interleukin-2 production	1	290.6×	0.006	TNFAIP3
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	290.6×	0.006	TNFAIP3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
ABRACL	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: 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	TNFAIP3, ABRACL

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)
TNFAIP3	1	—
ABRACL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.