◎ Sugi Atlas

Atlas / Disease / Mixed connective tissue disease

Mixed connective tissue disease

disease
On this page

Also known as MCTDsharp syndrome

Summary

Mixed connective tissue disease (MONDO:0005854) is a disease with 23 GWAS associations across 4 studies and 13 clinical trials. Top therapeutic interventions include cyclophosphamide anhydrous, yellow fever vaccine, and mhv-370. A subtype of rheumatic disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

  • Prevalence: 1-9 / 100 000 (Norway) [Orphanet-validated]
  • GWAS associations: 23
  • Phenotypes (HPO): 68
  • Clinical trials: 13

Clinical features

Epidemiology

Prevalence records

6 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Annual incidence1-9 / 1 000 0000.17NorwayValidated
Annual incidence1-9 / 100 0001.9United StatesValidated
Annual incidence1-9 / 1 000 0000.8FinlandValidated
Point prevalence1-9 / 100 0003NorwayValidated
Point prevalence1-9 / 100 0002.7JapanValidated
Point prevalence1-9 / 100 000EuropeNot yet validated

Signs & symptoms

Clinical features (HPO)

68 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO IDTermFrequency
HP:0000988Skin rashVery frequent (80-99%)
HP:0001369ArthritisVery frequent (80-99%)
HP:0002020Gastroesophageal refluxVery frequent (80-99%)
HP:0002094DyspneaVery frequent (80-99%)
HP:0002206Pulmonary fibrosisVery frequent (80-99%)
HP:0002960AutoimmunityVery frequent (80-99%)
HP:0003326MyalgiaVery frequent (80-99%)
HP:0003565Elevated erythrocyte sedimentation rateVery frequent (80-99%)
HP:0005263GastritisVery frequent (80-99%)
HP:0012378FatigueVery frequent (80-99%)
HP:0100324SclerodermaVery frequent (80-99%)
HP:0100749Chest painVery frequent (80-99%)
HP:0001945FeverFrequent (30-79%)
HP:0002102PleuritisFrequent (30-79%)
HP:0002829ArthralgiaFrequent (30-79%)
HP:0002923Rheumatoid factor positiveFrequent (30-79%)
HP:0007514Edema of the dorsum of handsFrequent (30-79%)
HP:0010702Increased circulating antibody levelFrequent (30-79%)
HP:0011838SclerodactylyFrequent (30-79%)
HP:0020151Anti-dsDNA antibody positivityFrequent (30-79%)
HP:0030880Raynaud phenomenonFrequent (30-79%)
HP:0033028Anti-U1 ribonucleoprotein antibody positivityFrequent (30-79%)
HP:0034076Anti-ribosome Po antibody positivityFrequent (30-79%)
HP:0034092Anti-cyclic citrullinated peptide antibody positivityFrequent (30-79%)
HP:0034093Anti-Ro52/TRIM21 antibody positivityFrequent (30-79%)
HP:0100614MyositisFrequent (30-79%)
HP:0100661Trigeminal neuralgiaFrequent (30-79%)
HP:0000217XerostomiaFrequent (30-79%)
HP:0000709PsychosisFrequent (30-79%)
HP:0001097Keratoconjunctivitis siccaFrequent (30-79%)
HP:0001386Joint swellingFrequent (30-79%)
HP:0000093ProteinuriaOccasional (5-29%)
HP:0000112NephropathyOccasional (5-29%)
HP:0000155Oral ulcerOccasional (5-29%)
HP:0000365Hearing impairmentOccasional (5-29%)
HP:0000716DepressionOccasional (5-29%)
HP:0000979PurpuraOccasional (5-29%)
HP:0001009TelangiectasiaOccasional (5-29%)
HP:0001250SeizureOccasional (5-29%)
HP:0001387Joint stiffnessOccasional (5-29%)
HP:0001596AlopeciaOccasional (5-29%)
HP:0001698Pericardial effusionOccasional (5-29%)
HP:0001701PericarditisOccasional (5-29%)
HP:0001744SplenomegalyOccasional (5-29%)
HP:0001873ThrombocytopeniaOccasional (5-29%)
HP:0001878Hemolytic anemiaOccasional (5-29%)
HP:0001882LeukopeniaOccasional (5-29%)
HP:0002092Pulmonary arterial hypertensionOccasional (5-29%)
HP:0002239Gastrointestinal hemorrhageOccasional (5-29%)
HP:0002315HeadacheOccasional (5-29%)

Identifiers

Disease identifiers

FieldValue
Canonical namemixed connective tissue disease
Mondo IDMONDO:0005854
EFOEFO:0007374
MeSHD008947
Orphanet809
DOIDDOID:3492
ICD-11891652224
NCITC84892
SNOMED CT398049005
UMLSC0026272
MedGen10069
GARD0007051
MedDRA10027754
NORD1451
Is cancer (heuristic)no

Also known as: MCTD · sharp syndrome

Data availability: 23 GWAS associations (4 studies) · 7 cell lines.

Disease family

This is a subtype of rheumatic disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

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

Related subtypes (29): palindromic rheumatism, rheumatic pulmonary valve disease, lupus erythematosus, 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, scleroderma, idiopathic juvenile osteoporosis, polymyalgia rheumatica, autoinflammatory syndrome, progeria-associated arthropathy, LAMA5-related multisystemic syndrome, rheumatic disease of mitral valve, isolated sternocostoclavicular hyperostosis

Genetics & variants

GWAS landscape

23 GWAS associations across 4 studies. Top hits map to 15 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs1825298465e-14EIF2S2P3 - HHEXT4.03
rs5624812876e-14SSX2IP - LPAR3A4.28
rs1396957003e-13EPIC1 - MIR3201T2.92
rs1418804934e-13LINC02315 - LRFN5-DTA3.2
rs1899235674e-13KCNMB2, KCNMB2-AS1C3.7
rs5489604015e-13TRIM55T3.24
rs1495274041e-12OR7E33P - ELL2P3A3.69
rs5423120232e-12UIMC1C3.73
rs5488973514e-12PTGISG4.47
rs5667063737e-12SLC4A10G2.6
rs1881075518e-12PTPRN2G3.89
rs1385598169e-12PFKPG2.64
rs5593542949e-12RPL34P27 - LSP1P1C2.37
rs5645258451e-11MYRIPT3.15
rs1872579551e-11NPM1P17 - SOX14A2.85
rs1398860542e-11BASP1A5.72
rs1872480602e-11PCLOG3.1
rs5663475932e-11LINC02140 - LINC02183A3.15
rs1839865442e-11LINC01940 - HDAC4C3.36
rs5700637693e-11LRP11C2.52
rs5561317634e-11PBLDG3.88
rs5501919764e-11CDH4A3.68
rs1829957514e-11SPOPC3.28

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90436640Zhou W20182,720399,404Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90482374Verma A2024430450,463Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480488Verma A2024290121,440Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90482373Verma A2024290121,440Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic23

MAF distribution

BucketVariants
common (>=0.05)0
low_freq (0.01-0.05)0
rare (<0.01)23
unknown0

Functional consequences

ConsequenceCount
intron_variant14
intergenic_variant9

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs1825298461092688993T>A0intergenic_variantEIF2S2P3 - HHEX5e-14Tier 4: intronic/intergenic
rs562481287184795499A>G0intron_variantSSX2IP - LPAR36e-14Tier 4: intronic/intergenic
rs1396957002248245558T>G0.001intergenic_variantEPIC1 - MIR32013e-13Tier 4: intronic/intergenic
rs1418804931441321786A>C,G0.001intergenic_variantLINC02315 - LRFN5-DT4e-13Tier 4: intronic/intergenic
rs1899235673178617931C>T0intron_variantKCNMB2, KCNMB2-AS14e-13Tier 4: intronic/intergenic
rs548960401866134077T>C0intron_variantTRIM555e-13Tier 4: intronic/intergenic
rs1495274041368266841A>G0.001intergenic_variantOR7E33P - ELL2P31e-12Tier 4: intronic/intergenic
rs5423120235176945540C>T0.001intron_variantUIMC12e-12Tier 4: intronic/intergenic
rs5488973512049546062G>A0intron_variantPTGIS4e-12Tier 4: intronic/intergenic
rs5667063732161559018G>A,C,T0.004intergenic_variantSLC4A107e-12Tier 4: intronic/intergenic
rs1881075517157650994G>A,T0intron_variantPTPRN28e-12Tier 4: intronic/intergenic
rs138559816103124523G>A0.001intron_variantPFKP9e-12Tier 4: intronic/intergenic
rs5593542941324992497C>T0.001intergenic_variantRPL34P27 - LSP1P19e-12Tier 4: intronic/intergenic
rs564525845339825776T>C,G0.001intron_variantMYRIP1e-11Tier 4: intronic/intergenic
rs1872579553137746077A>C,G0.001intergenic_variantNPM1P17 - SOX141e-11Tier 4: intronic/intergenic
rs139886054517234397A>G,T0intron_variantBASP12e-11Tier 4: intronic/intergenic
rs187248060782926086G>T0.001intron_variantPCLO2e-11Tier 4: intronic/intergenic
rs5663475931654473981A>G0.001intergenic_variantLINC02140 - LINC021832e-11Tier 4: intronic/intergenic
rs1839865442239034201C>T0.001intergenic_variantLINC01940 - HDAC42e-11Tier 4: intronic/intergenic
rs5700637696149834947C>T0.001intron_variantLRP113e-11Tier 4: intronic/intergenic
rs5561317631068298596G>A,T0intron_variantPBLD4e-11Tier 4: intronic/intergenic
rs5501919762061711085A>G,T0intron_variantCDH44e-11Tier 4: intronic/intergenic
rs1829957511749666679C>A0intron_variantSPOP4e-11Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

No druggable-target or therapeutic data for this disease’s cohort.

Clinical trials & evidence

Clinical trials

Clinical trials: 13.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified10
PHASE22
PHASE2/PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01862926PHASE2/PHASE3COMPLETEDRituximab Versus Cyclophosphamide in Connective Tissue Disease-ILD
NCT06672822PHASE2RECRUITINGIntralesional Injection of STS in Treatment of Calcinosis
NCT04988087PHASE2TERMINATEDA Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren’s Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD)
NCT03269630Not specifiedRECRUITINGNew Orleans Pulmonary Hypertension Biobank
NCT04402086Not specifiedRECRUITINGRheumatology Patient Registry and Biorepository
NCT05715463Not specifiedACTIVE_NOT_RECRUITINGRheumatology-based Adaptive Intervention for Social Determinants and Health Equity
NCT07180537Not specifiedRECRUITINGCreating Health Course Study for People With Rheumatological Conditions
NCT00522002Not specifiedCOMPLETEDCLUE Study: Connective Tissue Disease Leg Ulcer Etiology Study
NCT00582881Not specifiedCOMPLETEDCharacteristics and Disease Progression of Mixed Connective Tissue Disease and Systemic Lupus Erythematosus
NCT01697254Not specifiedCOMPLETEDThe CARRA Registry
NCT02494752Not specifiedUNKNOWNRole of Mesenchymal Stem Cells in Fat Grafting
NCT03430388Not specifiedCOMPLETEDYellow Fever Vaccine in Patients With Rheumatic Diseases
NCT05961267Not specifiedCOMPLETEDStudy of Gynecological Follow-up of Patients With Autoimmune Disease or Inflammatory Rheumatism

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
CYCLOPHOSPHAMIDE ANHYDROUS41
YELLOW FEVER VACCINE31
MHV-37021

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 25

This page pulls from 25 datasets indexed by BioBTree:

chembl_moleculecivic_evidenceclinical_trialsclinvardbsnpdoidefogardgenccgwasgwas_studyhgncicd11meddramedgenmeshmimmondomondochildmondoparentncitnordorphanetsctidumls