Scleroderma

Summary

Scleroderma (MONDO:0019340) is a disease with 1 cohort gene and 166 clinical trials. Top therapeutic interventions include 2-mercaptoethanesulfonic acid, anifrolumab, and bosentan.

At a glance

• Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 166

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	1.41	Worldwide	Validated
Point prevalence	1-5 / 10 000	42	Worldwide	Validated
Annual incidence	1-9 / 100 000	1.5	Australia	Validated
Point prevalence	1-5 / 10 000	23	Australia	Validated
Point prevalence	>1 / 1000	469	Specific population	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	scleroderma
Mondo ID	MONDO:0019340
EFO	EFO:1001993
Orphanet	801
DOID	DOID:419
NCIT	C26746
UMLS	C0011644
MedGen	3770
GARD	0018705
MedDRA	10039710
Is cancer (heuristic)	no

Also known as: scleroderma · scleroderma (disease)

Data availability: 1 ClinVar variant · 1 HPO phenotype.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › connective tissue disorder › rheumatic disorder › scleroderma

Related subtypes (29): palindromic rheumatism, rheumatic pulmonary valve disease, lupus erythematosus, mixed connective tissue disease, Reye syndrome, Wissler syndrome, acroosteolysis dominant type, chondrocalcinosis 2, Gorham-Stout disease, rheumatoid arthritis, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, juvenile idiopathic arthritis, sweet syndrome, dermatomyositis, IL10-related early-onset inflammatory bowel disease, unexplained long-lasting fever/inflammatory syndrome, myalgia-eosinophilia syndrome associated with tryptophan, reactive arthritis, rheumatic fever, intermittent hydrarthrosis, fibroblastic rheumatism, interstitial granulomatous dermatitis with arthritis, idiopathic juvenile osteoporosis, polymyalgia rheumatica, autoinflammatory syndrome, progeria-associated arthropathy, LAMA5-related multisystemic syndrome, rheumatic disease of mitral valve, isolated sternocostoclavicular hyperostosis

Subtypes (3): systemic sclerosis, neonatal scleroderma, localized scleroderma

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
196579	NM_001128225.3(SLC39A13):c.398C>T (p.Thr133Met)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC39A13	Orphanet:157965	SLC39A13-related spondylodysplastic Ehlers-Danlos syndrome

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
SLC39A13	HGNC:20859	ENSG00000165915	Q96H72	Zinc transporter ZIP13	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC39A13	Zinc transporter ZIP13	Functions as a zinc transporter transporting Zn(2+) from the Golgi apparatus to the cytosol and thus influences the zinc level at least in areas of the cytosol.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC39A13	Other/Unknown	no		ZIP

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
ascending aorta	1
metanephros cortex	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC39A13	248	ubiquitous	marker	metanephros cortex, ascending aorta, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC39A13	1,093

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC39A13	Q96H72	76.33

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
connective tissue development	1	4213.0×	0.001	SLC39A13
zinc ion transport	1	1532.0×	0.002	SLC39A13
zinc ion transmembrane transport	1	702.2×	0.002	SLC39A13
intracellular zinc ion homeostasis	1	481.5×	0.002	SLC39A13
brown fat cell differentiation	1	432.1×	0.002	SLC39A13

Therapeutics

Drugs indicated for this disease

0 approved, 3 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Nitroglycerin	Phase 3 (in late-stage trials)
Onabotulinumtoxina	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Atorvastatin, Lidocaine, Riociguat, Sildenafil.

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
SLC39A13	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	SLC39A13

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)
SLC39A13	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 166.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	108
PHASE2	16
PHASE3	10
PHASE2/PHASE3	8
PHASE1/PHASE2	8
PHASE1	8
PHASE4	4
EARLY_PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06763783	PHASE4	ENROLLING_BY_INVITATION	Vaccination Against Herpes Zoster in Patients With Inflammatory Rheumatic Diseases
NCT00204763	PHASE4	TERMINATED	Comparison of Esophageal and Anorectal Manometry Catheters
NCT01497743	PHASE4	WITHDRAWN	Probiotics in Patients With Moderate-to-severe Distention/ Bloating From Systemic Sclerosis
NCT04464434	PHASE4	COMPLETED	Upfront Autologous HSCT Versus Immunosuppression in Early Diffuse Cutaneous Systemic Sclerosis
NCT05098704	PHASE2/PHASE3	RECRUITING	Preventive Effect of Clopidogrel on the Systemic Sclerosis Development Risk
NCT05925803	PHASE3	ACTIVE_NOT_RECRUITING	Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)
NCT00319033	PHASE2/PHASE3	COMPLETED	Open-label Study With Bosentan in Interstitial Lung Disease
NCT00419419	PHASE3	COMPLETED	Phase III Study of a Topical Gel Formulation for Treatment and Prevention of Raynaud’s Phenomenon
NCT00498615	PHASE3	COMPLETED	A Rho-kinase Inhibitor (Fasudil) in the Treatment of Raynaud’s Phenomenon
NCT00501995	PHASE3	COMPLETED	High Dose Cyclophosphamide for Treatment of Scleroderma
NCT00740285	PHASE2/PHASE3	COMPLETED	Effectiveness and Safety of Lidocaine for Scleroderma
NCT01117298	PHASE3	COMPLETED	A Randomized Control Trial to Assess the Efficacy of Tadalafil in Raynaud’s Phenomenon in Scleroderma
NCT01570764	PHASE3	COMPLETED	Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease
NCT01862926	PHASE2/PHASE3	COMPLETED	Rituximab Versus Cyclophosphamide in Connective Tissue Disease-ILD
NCT01878526	PHASE3	COMPLETED	Gastroesophageal Reflux Treatment in Scleroderma
NCT02165111	PHASE3	COMPLETED	Efficacy of Botulinum Toxin In Scleroderma-Associated Raynaud’s Syndrome
NCT02302352	PHASE3	UNKNOWN	Effects of Probiotics on Gastrointestinal Symptoms and on the Immune System in Patients With Systemic Sclerosis
NCT02896205	PHASE3	COMPLETED	Study to Compare the Efficacy of Mycophenolate Mofetil in Systemic Sclerosis Related Early Interstitial Lung Disease
NCT03593902	PHASE2/PHASE3	TERMINATED	Cardiac Safe Transplants for Systemic Sclerosis
NCT03726398	PHASE2/PHASE3	WITHDRAWN	CompRehensive Phenotypic Characterization of Patients With Scleroderma-Associated ILD and PH
NCT05236491	PHASE2/PHASE3	UNKNOWN	COvid-19 Vaccine Booster in Immunocompromised Rheumatic Diseases
NCT05963048	PHASE2/PHASE3	COMPLETED	Rituxmab Versus IL-6 in Treating ILD
NCT04797286	PHASE2	RECRUITING	Sildenafil for Early Pulmonary Vascular Disease in Scleroderma
NCT06195072	PHASE2	RECRUITING	Platform Clinical Study for Conquering Scleroderma
NCT06328777	PHASE1/PHASE2	RECRUITING	RESET-SSc: An Open-Label Study to Evaluate the Safety and Efficacy of CABA-201, a CD19-CAR T Cell Therapy, in Subjects With Systemic Sclerosis
NCT06843239	PHASE2	RECRUITING	Tibulizumab Systemic Sclerosis Understanding and Response Evaluation (TibuSURE)
NCT06991114	PHASE2	RECRUITING	AlloNK®, an Allogeneic Non-genetically Modified, Cord Blood-derived NK Cell Therapy, in Combination With Rituximab, Studied in Relapsing Forms of B-cell Dependent Rheumatologic Diseases.
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT00007267	PHASE2	COMPLETED	Psychological Treatments for Scleroderma
NCT00043706	PHASE1/PHASE2	COMPLETED	Safety, Tolerability, and Pharmacokinetics of CAT-192 (Human Anti-TGF-Beta1 Monoclonal Antibody) in Patients With Early Stage Diffuse Systemic Sclerosis
NCT00764309	PHASE1/PHASE2	COMPLETED	Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis
NCT00775463	PHASE2	COMPLETED	Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine
NCT00883129	PHASE2	COMPLETED	Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II)
NCT01538719	PHASE1/PHASE2	COMPLETED	IL1-TRAP, Rilonacept, in Systemic Sclerosis
NCT01545427	PHASE2	TERMINATED	Proof of Concept Trial of Gleevec (Imatinib) in Active Diffuse Scleroderma
NCT01895244	PHASE2	COMPLETED	Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis
NCT02047708	PHASE2	COMPLETED	Zibotentan Better Renal Scleroderma Outcome Study
NCT02166229	PHASE1/PHASE2	WITHDRAWN	Divalproex Sodium in the Treatment of the Cutaneous Manifestations of Scleroderma
NCT02370693	PHASE2	COMPLETED	Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis
NCT02370784	PHASE2	COMPLETED	Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
2-MERCAPTOETHANESULFONIC ACID	4	2
ANIFROLUMAB	4	2
BOSENTAN	4	2
DASATINIB ANHYDROUS	4	2
AMBRISENTAN	4	1
BRENTUXIMAB VEDOTIN	4	1
CALCIPOTRIENE	4	1
CLOBETASOL PROPIONATE	4	1
DABIGATRAN ETEXILATE MESYLATE	4	1
DIVALPROEX SODIUM	4	1
DOMPERIDONE	4	1
FLUDARABINE PHOSPHATE	4	1
HYALURONIDASE	4	1
INEBILIZUMAB	4	1
LIDOCAINE	4	1
METHYLPREDNISOLONE	4	1
METHYLPREDNISOLONE ACETATE	4	1
PENICILLAMINE	4	1
RILONACEPT	4	1
RIOCIGUAT	4	1
STREPTOCOCCUS PNEUMONIAE POLYSACCHARIDE CONJUGATED TO CORYNEBACTERIUM DIPHTHERIAE CRM197	4	1
TACROLIMUS ANHYDROUS	4	1
TADALAFIL	4	1
TOFACITINIB	4	1
TREPROSTINIL DIOLAMINE	4	1
VARICELLA ZOSTER VIRUS ENVELOPE GLYCOPROTEIN E	4	1
ALGINIC ACID	3	1
AMLITELIMAB	3	1
CLOBETASOL	3	1
FASUDIL	3	1