Mitral valve prolapse
diseaseOn this page
Also known as barlow's syndromefloppy mitral valvemitral valve prolapse (disease)mitral valve prolapse syndromeprolapse, mitral valvevalve, prolapse Of mitral
Summary
Mitral valve prolapse (MONDO:0004910) is a disease with 13 cohort genes and 37 clinical trials. The dominant Reactome pathway is Collagen biosynthesis and modifying enzymes (3 cohort genes). Top therapeutic interventions include flecainide and metoprolol.
At a glance
- Cohort genes: 13
- ClinVar variants: 14
- Clinical trials: 37
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | mitral valve prolapse |
| Mondo ID | MONDO:0004910 |
| MeSH | D008945 |
| DOID | DOID:988 |
| ICD-11 | 1085590500 |
| NCIT | C50655 |
| SNOMED CT | 409712001, 8074002 |
| UMLS | C0026267 |
| MedGen | 7671 |
| Is cancer (heuristic) | no |
Also known as: barlow’s syndrome · floppy mitral valve · mitral valve prolapse · mitral valve prolapse (disease) · mitral valve prolapse syndrome · prolapse, mitral valve · valve, prolapse Of mitral
Data availability: 14 ClinVar variants · 3 GenCC gene-disease records · 1 HPO phenotype.
Disease family
An umbrella term covering 1 Mondo subtype.
Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart valve disorder › mitral valve disorder › mitral valve prolapse
Related subtypes (6): mitral valve stenosis, congenital anomaly of the mitral subvalvular apparatus, mitral atresia disorder, inherited mitral valve disease, rheumatic disease of mitral valve, mitral valve insufficiency
Subtypes (1): familial mitral valve prolapse
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
14 retrieved; paginated sample, class counts are floors:
4 likely pathogenic, 3 conflicting classifications of pathogenicity, 3 pathogenic, 2 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 373981 | NM_000138.5(FBN1):c.6800A>T (p.Asn2267Ile) | FBN1 | Pathogenic | no assertion criteria provided |
| 978559 | NM_000138.5(FBN1):c.3757_3760del (p.Gln1253fs) | FBN1 | Pathogenic | criteria provided, single submitter |
| 523241 | GRCh37/hg19 1p36.22(chr1:12019879-12028775) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 202493 | NM_001267550.2(TTN):c.94103_94107del (p.Ile31368fs) | TTN-AS1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 523328 | NM_000093.5(COL5A1):c.608G>T (p.Gly203Val) | COL5A1 | Likely pathogenic | criteria provided, single submitter |
| 523335 | NM_000138.5(FBN1):c.7829A>G (p.Glu2610Gly) | FBN1 | Likely pathogenic | criteria provided, single submitter |
| 374121 | NM_004586.3(RPS6KA3):c.533C>G (p.Ala178Gly) | RPS6KA3 | Likely pathogenic | criteria provided, single submitter |
| 373946 | NM_014112.5(TRPS1):c.1230G>A (p.Trp410Ter) | TRPS1 | Likely pathogenic | no assertion criteria provided |
| 523334 | NM_000138.5(FBN1):c.4388A>G (p.Asn1463Ser) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 568701 | NM_000138.5(FBN1):c.1900T>C (p.Ser634Pro) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 196579 | NM_001128225.3(SLC39A13):c.398C>T (p.Thr133Met) | SLC39A13 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 523536 | NM_030662.4(MAP2K2):c.514A>G (p.Lys172Glu) | MAP2K2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 373975 | NM_015922.3(NSDHL):c.1054C>G (p.Leu352Val) | NSDHL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 333652 | NM_001204.7(BMPR2):c.2948G>A (p.Arg983Gln) | BMPR2 | Likely benign | reviewed by expert panel |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 10 · Orphanet: 28 · 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 |
|---|---|---|---|---|
| DZIP1 | Moderate | Autosomal dominant | mitral valve prolapse | 3 |
| PDLIM7 | Limited | Autosomal dominant | mitral valve prolapse | 2 |
| TLL1 | Limited | Autosomal dominant | mitral valve prolapse | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TLL1 | Orphanet:99103 | Atrial septal defect, ostium secundum type |
| TLL1 | Orphanet:99106 | Atrial septal defect, ostium primum type |
| RPS6KA3 | Orphanet:192 | Coffin-Lowry syndrome |
| RPS6KA3 | Orphanet:276630 | Symptomatic form of Coffin-Lowry syndrome in female carriers |
| RPS6KA3 | Orphanet:777 | X-linked non-syndromic intellectual disability |
| BMPR2 | Orphanet:275777 | Heritable pulmonary arterial hypertension |
| BMPR2 | Orphanet:275786 | Drug- or toxin-induced pulmonary arterial hypertension |
| BMPR2 | Orphanet:31837 | Pulmonary venoocclusive disease |
| TRPS1 | Orphanet:502 | Trichorhinophalangeal syndrome type 2 |
| TRPS1 | Orphanet:77258 | Trichorhinophalangeal syndrome type 1 |
| NSDHL | Orphanet:139 | CHILD syndrome |
| NSDHL | Orphanet:251383 | CK syndrome |
| SLC39A13 | Orphanet:157965 | SLC39A13-related spondylodysplastic Ehlers-Danlos syndrome |
| COL5A1 | Orphanet:287 | Classical Ehlers-Danlos syndrome |
| FBN1 | Orphanet:1885 | Isolated ectopia lentis |
| FBN1 | Orphanet:2084 | Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome |
| FBN1 | Orphanet:2462 | Shprintzen-Goldberg syndrome |
| FBN1 | Orphanet:2623 | Geleophysic dysplasia |
| FBN1 | Orphanet:2833 | Stiff skin syndrome |
| FBN1 | Orphanet:284963 | Marfan syndrome type 1 |
| FBN1 | Orphanet:284979 | Neonatal Marfan syndrome |
| FBN1 | Orphanet:300382 | Progeroid and marfanoid aspect-lipodystrophy syndrome |
| FBN1 | Orphanet:3449 | Weill-Marchesani syndrome |
| FBN1 | Orphanet:91387 | Familial thoracic aortic aneurysm and aortic dissection |
| FBN1 | Orphanet:969 | Acromicric dysplasia |
| MAP2K2 | Orphanet:1340 | Cardiofaciocutaneous syndrome |
| MAP2K2 | Orphanet:638 | Neurofibromatosis-Noonan syndrome |
| PLOD1 | Orphanet:1900 | Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency |
Cohort genes → proteins
13 cohort genes, 12 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 13 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TLL1 | HGNC:11843 | ENSG00000038295 | O43897 | Tolloid-like protein 1 | gencc |
| DZIP1 | HGNC:20908 | ENSG00000134874 | Q86YF9 | Cilium assembly protein DZIP1 | gencc |
| PDLIM7 | HGNC:22958 | ENSG00000196923 | Q9NR12 | PDZ and LIM domain protein 7 | gencc |
| RPS6KA3 | HGNC:10432 | ENSG00000177189 | P51812 | Ribosomal protein S6 kinase alpha-3 | clinvar |
| BMPR2 | HGNC:1078 | ENSG00000204217 | Q13873 | Bone morphogenetic protein receptor type-2 | clinvar |
| TRPS1 | HGNC:12340 | ENSG00000104447 | Q9UHF7 | Zinc finger transcription factor Trps1 | clinvar |
| NSDHL | HGNC:13398 | ENSG00000147383 | Q15738 | Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating | clinvar |
| SLC39A13 | HGNC:20859 | ENSG00000165915 | Q96H72 | Zinc transporter ZIP13 | clinvar |
| COL5A1 | HGNC:2209 | ENSG00000130635 | P20908 | Collagen alpha-1(V) chain | clinvar |
| FBN1 | HGNC:3603 | ENSG00000166147 | P35555 | Fibrillin-1 | clinvar |
| TTN-AS1 | HGNC:44124 | ENSG00000237298 | TTN antisense RNA 1 | clinvar | |
| MAP2K2 | HGNC:6842 | ENSG00000126934 | P36507 | Dual specificity mitogen-activated protein kinase kinase 2 | clinvar |
| PLOD1 | HGNC:9081 | ENSG00000083444 | Q02809 | Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TLL1 | Tolloid-like protein 1 | Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. |
| DZIP1 | Cilium assembly protein DZIP1 | Molecular adapter that recruits protein complexes required for cilium assembly and function to the cilium basal body. |
| PDLIM7 | PDZ and LIM domain protein 7 | May function as a scaffold on which the coordinated assembly of proteins can occur. |
| RPS6KA3 | Ribosomal protein S6 kinase alpha-3 | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation thr… |
| BMPR2 | Bone morphogenetic protein receptor type-2 | On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. |
| TRPS1 | Zinc finger transcription factor Trps1 | Transcriptional repressor. |
| NSDHL | Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating | Catalyzes the NAD(P)(+)-dependent oxidative decarboxylation of the C4 methyl groups of 4-alpha-carboxysterols in post-squalene cholesterol biosynthesis. |
| 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. |
| COL5A1 | Collagen alpha-1(V) chain | Type V collagen is a member of group I collagen (fibrillar forming collagen). |
| FBN1 | Fibrillin-1 | Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues. |
| MAP2K2 | Dual specificity mitogen-activated protein kinase kinase 2 | Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. |
| PLOD1 | Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 | Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils. |
Protein-family classification
Druggable: 5 · Difficult: 3 · Unknown: 5 · Druggable fraction: 0.38
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 |
|---|---|---|---|
| Kinase | 3 | 6.4× | 0.051 |
| Protease | 1 | 2.8× | 0.504 |
| Transcription factor | 3 | 1.9× | 0.504 |
| Enzyme (other) | 1 | 0.9× | 0.847 |
| Other/Unknown | 5 | 0.7× | 0.938 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TLL1 | Protease | yes | EGF-type_Asp/Asn_hydroxyl_site, EGF, CUB_dom | |
| DZIP1 | Transcription factor | no | Znf_C2H2_type, DZIP1_N, DZIP_RILPL | |
| PDLIM7 | Transcription factor | no | PDZ, Znf_LIM, PDZ_sf | |
| RPS6KA3 | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS |
| BMPR2 | Kinase | yes | TGFB_receptor, Activin_recp, Prot_kinase_dom | |
| TRPS1 | Transcription factor | no | Znf_GATA, Znf_C2H2_type, Znf_NHR/GATA | |
| NSDHL | Enzyme (other) | yes | 1.1.1.170 | 3Beta_OHSteriod_DH/Estase, NAD(P)-bd_dom_sf, Lipid_A_modif_metabolic_enz |
| SLC39A13 | Other/Unknown | no | ZIP | |
| COL5A1 | Other/Unknown | no | Fib_collagen_C, Laminin_G, Collagen | |
| FBN1 | Other/Unknown | no | EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom | |
| TTN-AS1 | Other/Unknown | no | ||
| MAP2K2 | Kinase | yes | 2.7.12.2 | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf |
| PLOD1 | Other/Unknown | no | Procol_lys_dOase, Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph |
Expression context
Cohort genes with no expression data: 0.
13 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) | 13 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| left testis | 2 |
| ascending aorta | 2 |
| thoracic aorta | 2 |
| tendon of biceps brachii | 2 |
| stromal cell of endometrium | 2 |
| buccal mucosa cell | 1 |
| primordial germ cell in gonad | 1 |
| secondary oocyte | 1 |
| male germ cell | 1 |
| sperm | 1 |
| body of uterus | 1 |
| cartilage tissue | 1 |
| colonic mucosa | 1 |
| mucosa of sigmoid colon | 1 |
| lower lobe of lung | 1 |
| visceral pleura | 1 |
| calcaneal tendon | 1 |
| epithelium of mammary gland | 1 |
| mammary duct | 1 |
| adrenal tissue | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TLL1 | 162 | broad | marker | secondary oocyte, buccal mucosa cell, primordial germ cell in gonad |
| DZIP1 | 261 | ubiquitous | marker | sperm, male germ cell, left testis |
| PDLIM7 | 234 | ubiquitous | marker | body of uterus, ascending aorta, thoracic aorta |
| RPS6KA3 | 285 | ubiquitous | marker | cartilage tissue, mucosa of sigmoid colon, colonic mucosa |
| BMPR2 | 271 | ubiquitous | marker | visceral pleura, lower lobe of lung, tendon of biceps brachii |
| TRPS1 | 284 | ubiquitous | marker | mammary duct, epithelium of mammary gland, calcaneal tendon |
| NSDHL | 271 | ubiquitous | marker | cervix squamous epithelium, adrenal tissue, esophagus mucosa |
| SLC39A13 | 248 | ubiquitous | marker | metanephros cortex, ascending aorta, thoracic aorta |
| COL5A1 | 248 | ubiquitous | marker | stromal cell of endometrium, periodontal ligament, tendon of biceps brachii |
| FBN1 | 275 | ubiquitous | marker | synovial joint, skin of hip, decidua |
| TTN-AS1 | 174 | ubiquitous | marker | hindlimb stylopod muscle, gastrocnemius, right atrium auricular region |
| MAP2K2 | 291 | ubiquitous | marker | mucosa of transverse colon, right testis, left testis |
| PLOD1 | 279 | ubiquitous | marker | stromal cell of endometrium, smooth muscle tissue, apex of heart |
Protein interactions among cohort
Intra-cohort edges: 3.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| MAP2K2 | 3,789 |
| FBN1 | 3,640 |
| NSDHL | 3,566 |
| BMPR2 | 3,152 |
| RPS6KA3 | 2,713 |
| COL5A1 | 2,600 |
| TRPS1 | 2,588 |
| PDLIM7 | 2,400 |
| PLOD1 | 1,929 |
| DZIP1 | 1,380 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| COL5A1 | FBN1 | string_interaction |
| COL5A1 | PLOD1 | biogrid_interaction, string_interaction |
| PLOD1 | SLC39A13 | string_interaction |
Structural data
PDB: 8 · AlphaFold-only: 4 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| RPS6KA3 | P51812 | 15 |
| FBN1 | P35555 | 11 |
| BMPR2 | Q13873 | 7 |
| MAP2K2 | P36507 | 3 |
| PDLIM7 | Q9NR12 | 2 |
| NSDHL | Q15738 | 2 |
| TLL1 | O43897 | 1 |
| COL5A1 | P20908 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| PLOD1 | Q02809 | 93.04 |
| SLC39A13 | Q96H72 | 76.33 |
| DZIP1 | Q86YF9 | 65.55 |
| TRPS1 | Q9UHF7 | 49.12 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 106. Enrichment computed across 13 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Collagen biosynthesis and modifying enzymes | 3 | 51.1× | 0.002 | TLL1, COL5A1, PLOD1 |
| Signaling by NTRK1 (TRKA) | 2 | 39.4× | 0.046 | RPS6KA3, MAP2K2 |
| Signaling by NTRKs | 2 | 36.2× | 0.046 | RPS6KA3, MAP2K2 |
| Signaling by MAP2K mutants | 1 | 285.5× | 0.053 | MAP2K2 |
| Integrin cell surface interactions | 2 | 26.9× | 0.053 | COL5A1, FBN1 |
| L1CAM interactions | 2 | 24.0× | 0.053 | RPS6KA3, MAP2K2 |
| Degradation of the extracellular matrix | 2 | 23.6× | 0.053 | TLL1, FBN1 |
| Negative feedback regulation of MAPK pathway | 1 | 190.3× | 0.066 | MAP2K2 |
| CREB phosphorylation | 1 | 163.1× | 0.066 | RPS6KA3 |
| Prolonged ERK activation events | 1 | 142.8× | 0.066 | MAP2K2 |
| RSK activation | 1 | 142.8× | 0.066 | RPS6KA3 |
| Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway) | 1 | 126.9× | 0.066 | NSDHL |
| MAPK1 (ERK2) activation | 1 | 114.2× | 0.066 | MAP2K2 |
| Cholesterol biosynthesis via desmosterol (Bloch pathway) | 1 | 114.2× | 0.066 | NSDHL |
| Frs2-mediated activation | 1 | 95.2× | 0.067 | MAP2K2 |
| Uptake and function of anthrax toxins | 1 | 95.2× | 0.067 | MAP2K2 |
| CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 1 | 87.8× | 0.067 | RPS6KA3 |
| Gastrin-CREB signalling pathway via PKC and MAPK | 1 | 87.8× | 0.067 | RPS6KA3 |
| Uptake and actions of bacterial toxins | 1 | 81.6× | 0.068 | MAP2K2 |
| Anchoring fibril formation | 1 | 76.1× | 0.069 | TLL1 |
| ERK/MAPK targets | 1 | 67.2× | 0.071 | RPS6KA3 |
| RAF-independent MAPK1/3 activation | 1 | 63.4× | 0.071 | MAP2K2 |
| Signalling to ERKs | 1 | 60.1× | 0.071 | MAP2K2 |
| Fibronectin matrix formation | 1 | 57.1× | 0.071 | COL5A1 |
| Crosslinking of collagen fibrils | 1 | 57.1× | 0.071 | TLL1 |
| MAPK targets/ Nuclear events mediated by MAP kinases | 1 | 54.4× | 0.071 | RPS6KA3 |
| Signal transduction by L1 | 1 | 51.9× | 0.071 | MAP2K2 |
| Attachment of bacteria to epithelial cells | 1 | 49.6× | 0.071 | COL5A1 |
| Signaling by Receptor Tyrosine Kinases | 2 | 10.3× | 0.071 | RPS6KA3, MAP2K2 |
| Axon guidance | 2 | 9.0× | 0.071 | RPS6KA3, MAP2K2 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| skeletal system development | 4 | 41.9× | 3e-04 | RPS6KA3, TLL1, TRPS1, FBN1 |
| heart development | 4 | 26.2× | 9e-04 | DZIP1, PDLIM7, FBN1, MAP2K2 |
| collagen fibril organization | 3 | 56.2× | 9e-04 | TLL1, COL5A1, PLOD1 |
| collagen biosynthetic process | 2 | 175.5× | 0.002 | COL5A1, PLOD1 |
| blood vessel development | 2 | 62.4× | 0.013 | BMPR2, COL5A1 |
| lung alveolus development | 2 | 58.5× | 0.013 | BMPR2, FBN1 |
| integrin biosynthetic process | 1 | 1404.3× | 0.013 | COL5A1 |
| semi-lunar valve development | 1 | 1404.3× | 0.013 | BMPR2 |
| obsolete negative regulation of cell proliferation involved in heart valve morphogenesis | 1 | 702.2× | 0.016 | BMPR2 |
| regulation of lung blood pressure | 1 | 702.2× | 0.016 | BMPR2 |
| protein-containing complex localization to centriolar satellite | 1 | 702.2× | 0.016 | DZIP1 |
| negative regulation of endodermal cell differentiation | 1 | 702.2× | 0.016 | COL5A1 |
| regulation of translation in response to stress | 1 | 468.1× | 0.016 | RPS6KA3 |
| obsolete hydroxylysine biosynthetic process | 1 | 468.1× | 0.016 | PLOD1 |
| post-embryonic eye morphogenesis | 1 | 468.1× | 0.016 | FBN1 |
| pulmonary valve development | 1 | 351.1× | 0.016 | BMPR2 |
| obsolete sequestering of BMP in extracellular matrix | 1 | 351.1× | 0.016 | FBN1 |
| obsolete sequestering of TGFbeta in extracellular matrix | 1 | 351.1× | 0.016 | FBN1 |
| tendon development | 1 | 351.1× | 0.016 | COL5A1 |
| eye morphogenesis | 1 | 351.1× | 0.016 | COL5A1 |
| endochondral bone morphogenesis | 1 | 351.1× | 0.016 | BMPR2 |
| connective tissue development | 1 | 351.1× | 0.016 | SLC39A13 |
| regulation of Golgi inheritance | 1 | 351.1× | 0.016 | MAP2K2 |
| negative regulation of chondrocyte proliferation | 1 | 351.1× | 0.016 | BMPR2 |
| aortic valve development | 1 | 280.9× | 0.016 | BMPR2 |
| tricuspid valve morphogenesis | 1 | 280.9× | 0.016 | BMPR2 |
| ciliary basal body organization | 1 | 280.9× | 0.016 | DZIP1 |
| peptidyl-serine autophosphorylation | 1 | 280.9× | 0.016 | MAP2K2 |
| epithelial cell proliferation involved in lung morphogenesis | 1 | 280.9× | 0.016 | MAP2K2 |
| venous blood vessel development | 1 | 280.9× | 0.016 | BMPR2 |
Therapeutics
Drug target analysis
Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 10
Druggability breadth: 6 of 13 evidence-associated genes (46%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| RPS6KA3 | FEDRATINIB |
| BMPR2 | FEDRATINIB |
| MAP2K2 | VEMURAFENIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| MAP2K2 | 52 | 4 |
| RPS6KA3 | 46 | 4 |
| BMPR2 | 19 | 4 |
| TLL1 | 0 | 0 |
| DZIP1 | 0 | 0 |
| PDLIM7 | 0 | 0 |
| TRPS1 | 0 | 0 |
| NSDHL | 0 | 0 |
| SLC39A13 | 0 | 0 |
| COL5A1 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| FEDRATINIB | 4 | BMPR2, MAP2K2, RPS6KA3 |
| PALBOCICLIB | 4 | RPS6KA3 |
| ENTRECTINIB | 4 | RPS6KA3 |
| BOSUTINIB | 4 | BMPR2, MAP2K2, RPS6KA3 |
| GILTERITINIB | 4 | MAP2K2, RPS6KA3 |
| BRIGATINIB | 4 | RPS6KA3 |
| UPADACITINIB | 4 | RPS6KA3 |
| NINTEDANIB | 4 | BMPR2, MAP2K2, RPS6KA3 |
| SUNITINIB | 4 | BMPR2, MAP2K2, RPS6KA3 |
| QUIZARTINIB | 4 | RPS6KA3 |
| MIDOSTAURIN | 4 | RPS6KA3 |
| RUXOLITINIB | 4 | BMPR2, MAP2K2 |
| DEUCRAVACITINIB | 4 | BMPR2 |
| VEMURAFENIB | 4 | MAP2K2 |
| SELUMETINIB | 4 | MAP2K2 |
| TRAMETINIB | 4 | MAP2K2 |
| COBIMETINIB | 4 | MAP2K2 |
| BINIMETINIB | 4 | MAP2K2 |
| DASATINIB | 4 | MAP2K2 |
| AXITINIB | 4 | MAP2K2 |
| NERATINIB | 4 | MAP2K2 |
| VANDETANIB | 4 | MAP2K2 |
| ENZASTAURIN | 3 | RPS6KA3 |
| FASUDIL | 3 | RPS6KA3 |
| ALVOCIDIB | 3 | RPS6KA3 |
| ALISERTIB | 3 | RPS6KA3 |
| DOVITINIB | 3 | BMPR2, MAP2K2, RPS6KA3 |
| LESTAURTINIB | 3 | BMPR2, MAP2K2, RPS6KA3 |
| RUBOXISTAURIN | 3 | RPS6KA3 |
| LINIFANIB | 3 | BMPR2, MAP2K2 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| RPS6KA3 | 770 | Binding:768, Functional:1, ADMET:1 |
| MAP2K2 | 615 | Binding:581, Functional:33, ADMET:1 |
| BMPR2 | 166 | Binding:165, ADMET:1 |
| TLL1 | 5 | Binding:5 |
| PLOD1 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| RPS6KA3 | 2.7.11.1 | non-specific serine/threonine protein kinase |
| NSDHL | 1.1.1.170 | 3beta-hydroxysteroid-4alpha-carboxylate 3-dehydrogenase (decarboxylating) |
| MAP2K2 | 2.7.12.2 | mitogen-activated protein kinase kinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| RPS6KA3 | 770 |
| BMPR2 | 166 |
| MAP2K2 | 615 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 12; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
30 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| FEDRATINIB | 4 | BMPR2, MAP2K2, RPS6KA3 |
| PALBOCICLIB | 4 | RPS6KA3 |
| ENTRECTINIB | 4 | RPS6KA3 |
| BOSUTINIB | 4 | BMPR2, MAP2K2, RPS6KA3 |
| GILTERITINIB | 4 | MAP2K2, RPS6KA3 |
| BRIGATINIB | 4 | RPS6KA3 |
| UPADACITINIB | 4 | RPS6KA3 |
| NINTEDANIB | 4 | BMPR2, MAP2K2, RPS6KA3 |
| SUNITINIB | 4 | BMPR2, MAP2K2, RPS6KA3 |
| QUIZARTINIB | 4 | RPS6KA3 |
| MIDOSTAURIN | 4 | RPS6KA3 |
| RUXOLITINIB | 4 | BMPR2, MAP2K2 |
| DEUCRAVACITINIB | 4 | BMPR2 |
| VEMURAFENIB | 4 | MAP2K2 |
| SELUMETINIB | 4 | MAP2K2 |
| TRAMETINIB | 4 | MAP2K2 |
| COBIMETINIB | 4 | MAP2K2 |
| BINIMETINIB | 4 | MAP2K2 |
| DASATINIB | 4 | MAP2K2 |
| AXITINIB | 4 | MAP2K2 |
| NERATINIB | 4 | MAP2K2 |
| VANDETANIB | 4 | MAP2K2 |
| ENZASTAURIN | 3 | RPS6KA3 |
| FASUDIL | 3 | RPS6KA3 |
| ALVOCIDIB | 3 | RPS6KA3 |
| ALISERTIB | 3 | RPS6KA3 |
| DOVITINIB | 3 | BMPR2, MAP2K2, RPS6KA3 |
| LESTAURTINIB | 3 | BMPR2, MAP2K2, RPS6KA3 |
| RUBOXISTAURIN | 3 | RPS6KA3 |
| LINIFANIB | 3 | BMPR2, MAP2K2 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 3 | RPS6KA3, BMPR2, MAP2K2 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 2 | TLL1, NSDHL |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 8 | DZIP1, PDLIM7, TRPS1, SLC39A13, COL5A1, FBN1, TTN-AS1, PLOD1 |
Undrugged target profiles
10 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| TLL1 | 5 | — |
| DZIP1 | 0 | — |
| PDLIM7 | 0 | — |
| TRPS1 | 0 | — |
| NSDHL | 0 | — |
| SLC39A13 | 0 | — |
| COL5A1 | 0 | — |
| FBN1 | 0 | — |
| TTN-AS1 | 0 | — |
| PLOD1 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 37.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 34 |
| PHASE1 | 2 |
| PHASE3 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05631730 | PHASE3 | RECRUITING | Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse |
| NCT01500148 | PHASE1 | COMPLETED | St. Jude Medical Percutaneous Mitral Valve Repair Study |
| NCT04299334 | PHASE1 | UNKNOWN | Neochordae Technique in Mitral Valve Repair |
| NCT03113552 | Not specified | RECRUITING | Prognostic Impact of the Location of Mitral Valve Prolapse on the Long-term Results of Mitral Plasty |
| NCT04190602 | Not specified | RECRUITING | Multicenter Post-Market Observational Registry of the NeoChord Artificial Chordae Delivery System |
| NCT04852731 | Not specified | RECRUITING | STretch and Myocardial Characterization in Arrythmogenic Mitral Valve Prolapse-2 |
| NCT06255457 | Not specified | RECRUITING | Ventricular Arrhythmias in Patients Undergoing Mitral Valve Surgery |
| NCT06341166 | Not specified | RECRUITING | Multiparametric SCores for Prediction of Myocardial fIbrosis in Patients With MITral vAlve pRolapse |
| NCT06378996 | Not specified | RECRUITING | Arrhythmic Mitral Valve Prolapse Detection Using Long-term Ambulatory Rhythm Monitoring |
| NCT06738537 | Not specified | RECRUITING | Patient-Centered Approach for Treatment Decisions in Mitral Valve Prolapse |
| NCT06741709 | Not specified | NOT_YET_RECRUITING | A Study of Mitral Annular Disjunction in Mitral Valve Prolapse Patients and Arrhythmia Risk |
| NCT07068633 | Not specified | NOT_YET_RECRUITING | Korea VHD Echo Study: Surveillance of Aortic, Mitral & Tricuspid Patients - Insights From Real-world Practice |
| NCT07103733 | Not specified | RECRUITING | PRIMARY Ancillary Substudy |
| NCT07366723 | Not specified | ACTIVE_NOT_RECRUITING | The Role of cardIac magNeTic rEsonance in surGical Decision Making in Patients With Severe pRimAry miTral rEgurgitation |
| NCT07384871 | Not specified | RECRUITING | AI-Based Shape and Function Analysis of Mitral Valve Prolapse Using 3D Ultrasound |
| NCT00665301 | Not specified | COMPLETED | Cardiac Output Pulmonary Arterial Catheter Compared to FloWave™ 1000 |
| NCT00799565 | Not specified | COMPLETED | Mitral Valve Prolapse (MVP) - France Study |
| NCT01719211 | Not specified | UNKNOWN | Genetic Basis of Mitral Valve Prolapse |
| NCT02105480 | Not specified | COMPLETED | Automated Algorithm Based Analysis of Phonocardiograms of Newborns |
| NCT02432196 | Not specified | COMPLETED | CE Mark Study for the Harpoon Medical Device in Poland |
| NCT02499419 | Not specified | UNKNOWN | Exercise Capacity Evaluation in Patients With Non-rheumatic Mitral Valve Prolapse (MVP) |
| NCT02512341 | Not specified | COMPLETED | Automatic Differentiation of Innocent and Pathologic Murmurs in Pediatrics |
| NCT02552771 | Not specified | UNKNOWN | The Canadian Mitral Research Alliance (CAMRA) Trial CardioLink-2 |
| NCT02768870 | Not specified | COMPLETED | CE Mark Study for the Harpoon Medical Device |
| NCT02771275 | Not specified | COMPLETED | Safety and Early Feasibility Study of the Harpoon Medical Device (EFS) |
| NCT02879825 | Not specified | COMPLETED | Myocardial Characterization of Arrhythmogenic Mitral Valve Prolapse (STAMP: STretch and Myocardial Characterization in Arrhythmogenic Mitral Valve Prolapse) |
| NCT03285724 | Not specified | TERMINATED | Safety and Performance Study of the Harpoon Mitral Valve Repair System |
| NCT03470155 | Not specified | COMPLETED | Operative Mitral Valve Reconstruction in Functional mv Insufficiency With Reduced Systolic Ventricle Function |
| NCT03506217 | Not specified | UNKNOWN | Using Pulse Counter Vigileo-Flotrac System in Transapical Off-pump Minimally Invasive Mitral Valve Repair |
| NCT03609931 | Not specified | UNKNOWN | Patient Specific Mitral Valve Modeling for Surgical Planning and Training |
| NCT03884426 | Not specified | UNKNOWN | Genetic and Phenotypic Characteristics of Mitral Valve Prolapse |
| NCT04067635 | Not specified | UNKNOWN | Primary Mitral Regurgitation Repair |
| NCT04231903 | Not specified | COMPLETED | Myocardial Protection in Minimally Invasive Mitral Valve Surgery |
| NCT04770961 | Not specified | UNKNOWN | Erector Spinae Plane Block for Minimally Invasive Mitral Valve Surgery |
| NCT05425628 | Not specified | UNKNOWN | European FIH Study - NeoChord Transcatheter Mitral Repair System for Symptomatic Mitral Regurgitation |
| NCT05562804 | Not specified | UNKNOWN | Mitral Valve Prolapse, Arrhythmias and Mitral Valve Surgery |
| NCT06436573 | Not specified | COMPLETED | Mitro-annular Disjunction in Cardiac Magnetic Resonance |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| FLECAINIDE | 4 | 3 |
| METOPROLOL | 4 | 2 |