Stuve-Wiedemann syndrome 2

Summary

Stuve-Wiedemann syndrome 2 (MONDO:0030756) is a disease caused by IL6ST (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: IL6ST (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Stuve-Wiedemann syndrome 2
Mondo ID	MONDO:0030756
OMIM	619751
UMLS	C5676919
MedGen	1805977
Is cancer (heuristic)	no

Also known as: Stuve-Wiedemann syndrome 2 · STWS2

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

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › Stuve-Wiedemann syndrome › Stuve-Wiedemann syndrome 2

Related subtypes (1): Stüve-Wiedemann syndrome 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:

5 uncertain significance, 3 pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1341692	NM_002184.4(IL6ST):c.1699+4A>G	IL6ST	Pathogenic	no assertion criteria provided
4057198	NM_002184.4(IL6ST):c.1124C>G (p.Ser375Ter)	IL6ST	Pathogenic	criteria provided, single submitter
635407	NM_002184.4(IL6ST):c.841C>T (p.Arg281Ter)	IL6ST	Pathogenic	criteria provided, multiple submitters, no conflicts
3779767	NM_002184.4(IL6ST):c.2254_2258del (p.Asn752fs)	IL6ST	Likely pathogenic	criteria provided, single submitter
281250	NM_025114.4(CEP290):c.1092T>G (p.Ile364Met)	CEP290	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1432476	NM_025114.4(CEP290):c.5413C>T (p.Leu1805Phe)	CEP290	Uncertain significance	criteria provided, multiple submitters, no conflicts
1357226	NM_014806.5(RUSC2):c.3983G>A (p.Cys1328Tyr)	CIMIP2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1437640	NM_002184.4(IL6ST):c.283G>A (p.Ala95Thr)	IL6ST	Uncertain significance	criteria provided, multiple submitters, no conflicts
2575046	NM_002184.4(IL6ST):c.1614G>T (p.Glu538Asp)	IL6ST	Uncertain significance	criteria provided, multiple submitters, no conflicts
3602583	NM_002184.4(IL6ST):c.2728G>C (p.Val910Leu)	IL6ST	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 8 · 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
IL6ST	Strong	Autosomal recessive	Stuve-Wiedemann syndrome 2	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL6ST	Orphanet:656283	Autosomal recessive combined immunodeficiency due to complete IL6ST deficiency
IL6ST	Orphanet:656300	Autosomal recessive combined immunodeficiency due to partial IL6ST deficiency
IL6ST	Orphanet:656313	Autosomal dominant combined immunodeficiency due to partial IL6ST deficiency
CEP290	Orphanet:110	Bardet-Biedl syndrome
CEP290	Orphanet:2318	Joubert syndrome with oculorenal defect
CEP290	Orphanet:3156	Senior-Loken syndrome
CEP290	Orphanet:564	Meckel syndrome
CEP290	Orphanet:65	Leber congenital amaurosis

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IL6ST	HGNC:6021	ENSG00000134352	P40189	Interleukin-6 receptor subunit beta	gencc,clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	clinvar
CIMIP2B	HGNC:34242	ENSG00000215187	A8MTA8	Ciliary microtubule inner protein 2B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL6ST	Interleukin-6 receptor subunit beta	Signal-transducing molecule.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
CIMIP2B	Ciliary microtubule inner protein 2B	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Antibody/Immunoglobulin	1	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IL6ST	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, FN3_dom, IgC2-like_lig-bd
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
CIMIP2B	Other/Unknown	no		CMI2A-C-like_dom

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
germinal epithelium of ovary	1
parietal pleura	1
pleura	1
male germ line stem cell (sensu Vertebrata) in testis	1
right uterine tube	1
ventricular zone	1
adrenal tissue	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL6ST	295	ubiquitous	marker	parietal pleura, pleura, germinal epithelium of ovary
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
CIMIP2B	167	tissue_specific	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP290	2,778
IL6ST	1,530
CIMIP2B	342

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL6ST	P40189	20
CIMIP2B	A8MTA8	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CEP290	O15078	60.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 3 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
MAPK1 (ERK2) activation	1	571.0×	0.011	IL6ST
MAPK3 (ERK1) activation	1	519.1×	0.011	IL6ST
Interleukin-27 signaling	1	519.1×	0.011	IL6ST
Interleukin-6 signaling	1	475.8×	0.011	IL6ST
Interleukin-35 Signalling	1	475.8×	0.011	IL6ST
IL-6-type cytokine receptor ligand interactions	1	317.2×	0.014	IL6ST
Centrosome maturation	1	126.9×	0.026	CEP290
Activation of STAT3 by cadherin engagement	1	81.6×	0.026	IL6ST
Loss of Nlp from mitotic centrosomes	1	79.3×	0.026	CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.026	CEP290
AURKA Activation by TPX2	1	76.1×	0.026	CEP290
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.026	CEP290
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.026	CEP290
Mitotic G2-G2/M phases	1	63.4×	0.026	CEP290
G2/M Transition	1	63.4×	0.026	CEP290
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.026	CEP290
Anchoring of the basal body to the plasma membrane	1	56.5×	0.026	CEP290
Cilium Assembly	1	54.4×	0.026	CEP290
Mitotic Prometaphase	1	34.6×	0.037	CEP290
Organelle biogenesis and maintenance	1	33.0×	0.037	CEP290
M Phase	1	33.0×	0.037	CEP290
Cell Cycle, Mitotic	1	24.1×	0.049	CEP290
Cell Cycle	1	18.0×	0.062	CEP290
Innate Immune System	1	12.8×	0.083	CEP290
Neutrophil degranulation	1	11.5×	0.088	CEP290
Immune System	1	6.5×	0.148	CEP290

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 interleukin-6-mediated signaling pathway	1	4213.0×	0.003	IL6ST
obsolete ciliary basal body-plasma membrane docking	1	4213.0×	0.003	CEP290
ciliary transition zone assembly	1	2808.7×	0.003	CEP290
oncostatin-M-mediated signaling pathway	1	2106.5×	0.003	IL6ST
leukemia inhibitory factor signaling pathway	1	2106.5×	0.003	IL6ST
interleukin-11-mediated signaling pathway	1	1685.2×	0.003	IL6ST
ciliary neurotrophic factor-mediated signaling pathway	1	1685.2×	0.003	IL6ST
pronephros development	1	1203.7×	0.003	CEP290
interleukin-27-mediated signaling pathway	1	1203.7×	0.003	IL6ST
regulation of establishment of protein localization	1	1203.7×	0.003	CEP290
positive regulation of adaptive immune response	1	1053.2×	0.003	IL6ST
otic vesicle formation	1	1053.2×	0.003	CEP290
intestinal epithelial cell development	1	766.0×	0.003	IL6ST
T-helper 17 cell lineage commitment	1	766.0×	0.003	IL6ST
positive regulation of acute inflammatory response	1	702.2×	0.003	IL6ST
positive regulation of astrocyte differentiation	1	702.2×	0.003	IL6ST
positive regulation of platelet aggregation	1	648.1×	0.004	IL6ST
hindbrain development	1	561.7×	0.004	CEP290
interleukin-6-mediated signaling pathway	1	561.7×	0.004	IL6ST
eye photoreceptor cell development	1	421.3×	0.005	CEP290
positive regulation of cardiac muscle hypertrophy	1	366.4×	0.005	IL6ST
positive regulation of intracellular protein transport	1	337.0×	0.005	CEP290
cell surface receptor signaling pathway via STAT	1	280.9×	0.006	IL6ST
glycogen metabolic process	1	263.3×	0.006	IL6ST
positive regulation of vascular endothelial growth factor production	1	247.8×	0.006	IL6ST
response to cytokine	1	187.2×	0.008	IL6ST
camera-type eye development	1	179.3×	0.008	CEP290
positive regulation of Notch signaling pathway	1	175.5×	0.008	IL6ST
non-motile cilium assembly	1	145.3×	0.009	CEP290
positive regulation of T cell proliferation	1	129.6×	0.010	IL6ST

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IL6ST	0	0
CEP290	0	0
CIMIP2B	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
IL6ST	21	Binding:21

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	IL6ST
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CEP290, CIMIP2B

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
IL6ST	21	—
CEP290	0	—
CIMIP2B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.