autoinflammatory syndrome, familial, X-linked, Behcet-like 2

Summary

autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (MONDO:0024770) is a disease caused by ELF4 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ELF4 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autoinflammatory syndrome, familial, X-linked, Behcet-like 2
Mondo ID	MONDO:0024770
OMIM	301074
Orphanet	676125
UMLS	C5575495
MedGen	1808082
GARD	0025462
Is cancer (heuristic)	no

Also known as: AIFBL2 · autoinflammatory syndrome, familial, X-linked, Behcet-like 2 · deficiency 1n ELF4, X-linked

Data availability: 10 ClinVar variants · 1 GenCC gene-disease record.

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, X-linked, Behcet-like 2

Related subtypes (1): 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

10 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 4 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1676293	NM_001421.4(ELF4):c.752G>C (p.Trp251Ser)	ELF4	Pathogenic	no assertion criteria provided
1676294	NM_001421.4(ELF4):c.1015del (p.Ala339fs)	ELF4	Pathogenic	no assertion criteria provided
1676295	NM_001421.4(ELF4):c.691T>C (p.Trp231Arg)	ELF4	Pathogenic	no assertion criteria provided
4848750	NC_000023.10:g.(?129197929)(129215514_129244299)del	ELF4	Pathogenic	criteria provided, single submitter
2441684	NM_001421.4(ELF4):c.724G>A (p.Val242Met)	ELF4	Uncertain significance	criteria provided, single submitter
2664696	NM_001421.4(ELF4):c.668A>T (p.Asn223Ile)	ELF4	Uncertain significance	criteria provided, single submitter
3393288	NM_001421.4(ELF4):c.710G>T (p.Gly237Val)	ELF4	Uncertain significance	criteria provided, single submitter
3393333	NM_001421.4(ELF4):c.1936C>T (p.Pro646Ser)	ELF4	Uncertain significance	criteria provided, single submitter
4846786	NM_001421.4(ELF4):c.617G>A (p.Gly206Asp)	ELF4	Uncertain significance	criteria provided, single submitter
4846787	NM_001421.4(ELF4):c.710G>C (p.Gly237Ala)	ELF4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
ELF4	Strong	X-linked	autoinflammatory syndrome, familial, X-linked, Behcet-like 2	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ELF4	Orphanet:632	Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia
ELF4	Orphanet:676125	X-linked immune dysregulation with inflammatory bowel disease due to ELF4 deficiency

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
ELF4	HGNC:3319	ENSG00000102034	Q99607	ETS-related transcription factor Elf-4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ELF4	ETS-related transcription factor Elf-4	Transcriptional activator that binds to DNA sequences containing the consensus 5’-WGGA-3'.

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)
ELF4	Transcription factor	no		Ets_dom, TF_Elf_N, WH-like_DNA-bd_sf

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
blood	1
endometrium epithelium	1
granulocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ELF4	246	ubiquitous	marker	endometrium epithelium, granulocyte, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ELF4	1,164

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ELF4	Q99607	49.77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
NK T cell proliferation	1	5617.3×	0.001	ELF4
natural killer cell proliferation	1	3370.4×	0.001	ELF4
negative regulation of interleukin-1 beta production	1	510.7×	0.007	ELF4
negative regulation of interleukin-6 production	1	351.1×	0.007	ELF4
negative regulation of tumor necrosis factor production	1	251.5×	0.008	ELF4
negative regulation of inflammatory response	1	137.0×	0.012	ELF4
cell differentiation	1	29.1×	0.045	ELF4
positive regulation of DNA-templated transcription	1	27.9×	0.045	ELF4
positive regulation of transcription by RNA polymerase II	1	14.9×	0.075	ELF4
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ELF4

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
ELF4	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	ELF4

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)
ELF4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.