Autoinflammatory syndrome with immunodeficiency

Summary

Autoinflammatory syndrome with immunodeficiency (MONDO:0800130) is a disease caused by SOCS1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SOCS1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autoinflammatory syndrome with immunodeficiency
Mondo ID	MONDO:0800130
OMIM	619375
UMLS	C5543547
MedGen	1784363
GARD	0026448
Is cancer (heuristic)	no

Data availability: 18 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 with immunodeficiency

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, autoinflammatory syndrome, familial, Behcet-like, CEBPE-associated autoinflammation-immunodeficiency-neutrophil dysfunction syndrome, type 1 interferonopathy, autoinflammatory disease, X-linked, 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

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

18 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 4 likely pathogenic, 4 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
977213	NM_003745.2(SOCS1):c.24del (p.Ala9fs)	LOC130058479	Pathogenic	criteria provided, single submitter
1172797	NM_003745.2(SOCS1):c.480_481insGCGGC (p.Met161fs)	SOCS1	Pathogenic	no assertion criteria provided
977212	NM_003745.2(SOCS1):c.368C>G (p.Pro123Arg)	SOCS1	Pathogenic	criteria provided, single submitter
977214	NM_003745.2(SOCS1):c.476_480dup (p.Met161fs)	SOCS1	Pathogenic	criteria provided, multiple submitters, no conflicts
2627601	NM_003745.2(SOCS1):c.560G>A (p.Gly187Asp)	LOC130058478	Likely pathogenic	criteria provided, single submitter
1120219	NM_003745.2(SOCS1):c.192C>G (p.Tyr64Ter)	SOCS1	Likely pathogenic	criteria provided, single submitter
3068305	NM_003745.2(SOCS1):c.454G>T (p.Glu152Ter)	SOCS1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3340478	NM_003745.2(SOCS1):c.147_153dup (p.Asp52fs)	SOCS1	Likely pathogenic	no assertion criteria provided
3393334	NM_003745.2(SOCS1):c.604G>A (p.Asp202Asn)	LOC130058478	Uncertain significance	criteria provided, single submitter
4077270	NM_003745.2(SOCS1):c.604G>T (p.Asp202Tyr)	LOC130058478	Uncertain significance	criteria provided, multiple submitters, no conflicts
3064716	NM_003745.2(SOCS1):c.108_137del (p.Arg38_Ala47del)	LOC130058479	Uncertain significance	criteria provided, single submitter
3236586	NM_003745.2(SOCS1):c.70G>A (p.Glu24Lys)	LOC130058479	Uncertain significance	criteria provided, single submitter
432971	NM_003745.2(SOCS1):c.108del (p.Ala37fs)	LOC130058479	Uncertain significance	criteria provided, single submitter
2431403	NM_003745.2(SOCS1):c.281G>T (p.Arg94Leu)	SOCS1	Uncertain significance	criteria provided, single submitter
3393105	NM_003745.2(SOCS1):c.112_132dup (p.Ala44_Val45insArgProArgProCysProAla)	SOCS1	Uncertain significance	criteria provided, single submitter
3393337	NM_003745.2(SOCS1):c.313G>T (p.Asp105Tyr)	SOCS1	Uncertain significance	criteria provided, single submitter
3775868	NM_003745.2(SOCS1):c.251T>C (p.Leu84Pro)	SOCS1	Uncertain significance	criteria provided, single submitter
4819816	NM_003745.2(SOCS1):c.539A>C (p.Gln180Pro)	SOCS1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
SOCS1	Strong	Autosomal dominant	autoinflammatory syndrome with immunodeficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOCS1	Orphanet:619948	Early-onset autoimmunity-autoinflammation-immunodeficiency syndrome due to SOCS1 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
SOCS1	HGNC:19383	ENSG00000185338	O15524	Suppressor of cytokine signaling 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SOCS1	Suppressor of cytokine signaling 1	Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF).

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SOCS1	Scaffold/PPI	no		SH2, SOCS_box, SOCS1_SH2

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
endocervix	1
sperm	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SOCS1	211	ubiquitous	marker	type B pancreatic cell, sperm, endocervix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOCS1	3,435

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SOCS1	O15524	84.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. 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
Regulation of IFNG signaling	1	815.7×	0.010	SOCS1
Regulation of KIT signaling	1	601.0×	0.010	SOCS1
Signaling by CSF3 (G-CSF)	1	571.0×	0.010	SOCS1
Growth hormone receptor signaling	1	475.8×	0.010	SOCS1
Regulation of IFNA/IFNB signaling	1	439.2×	0.010	SOCS1
Inactivation of CSF3 (G-CSF) signaling	1	439.2×	0.010	SOCS1
Interleukin-7 signaling	1	317.2×	0.012	SOCS1
Signaling by SCF-KIT	1	248.3×	0.013	SOCS1
Toll Like Receptor TLR6:TLR2 Cascade	1	175.7×	0.013	SOCS1
Toll Like Receptor 2 (TLR2) Cascade	1	173.0×	0.013	SOCS1
Toll Like Receptor TLR1:TLR2 Cascade	1	167.9×	0.013	SOCS1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	152.3×	0.013	SOCS1
Interferon alpha/beta signaling	1	152.3×	0.013	SOCS1
Toll Like Receptor 4 (TLR4) Cascade	1	131.3×	0.013	SOCS1
Interferon gamma signaling	1	125.5×	0.013	SOCS1
Toll-like Receptor Cascades	1	124.1×	0.013	SOCS1
Interferon Signaling	1	120.2×	0.013	SOCS1
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.015	SOCS1
Class I MHC mediated antigen processing & presentation	1	70.1×	0.020	SOCS1
Signaling by Interleukins	1	64.2×	0.021	SOCS1
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.025	SOCS1
Cytokine Signaling in Immune system	1	40.8×	0.030	SOCS1
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.032	SOCS1
Adaptive Immune System	1	29.8×	0.038	SOCS1
Innate Immune System	1	25.5×	0.042	SOCS1
Immune System	1	13.0×	0.080	SOCS1
Signal Transduction	1	10.2×	0.098	SOCS1

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 CD8-positive, alpha-beta T cell differentiation	1	5617.3×	0.002	SOCS1
positive regulation of CD4-positive, alpha-beta T cell differentiation	1	2808.7×	0.002	SOCS1
positive regulation of regulatory T cell differentiation	1	936.2×	0.004	SOCS1
negative regulation of receptor signaling pathway via JAK-STAT	1	887.0×	0.004	SOCS1
macrophage differentiation	1	468.1×	0.006	SOCS1
negative regulation of insulin receptor signaling pathway	1	374.5×	0.006	SOCS1
cellular response to amino acid stimulus	1	306.4×	0.006	SOCS1
cell surface receptor signaling pathway via JAK-STAT	1	290.6×	0.006	SOCS1
regulation of cytokine production	1	247.8×	0.006	SOCS1
fat cell differentiation	1	181.2×	0.007	SOCS1
cytokine-mediated signaling pathway	1	130.6×	0.009	SOCS1
protein ubiquitination	1	41.4×	0.026	SOCS1
intracellular signal transduction	1	38.1×	0.026	SOCS1

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
SOCS1	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	SOCS1

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)
SOCS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.