Epidermolysis bullosa simplex with nail dystrophy
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Also known as EBSNDepidermolysis bullosa simplex 5D, generalised intermediate, autosomal recessiveepidermolysis bullosa simplex 5D, generalized intermediate, autosomal recessive
Summary
Epidermolysis bullosa simplex with nail dystrophy (MONDO:0014661) is a disease with 13 cohort genes.
At a glance
- Cohort genes: 13
- ClinVar variants: 5,755
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | epidermolysis bullosa simplex with nail dystrophy |
| Mondo ID | MONDO:0014661 |
| OMIM | 616487 |
| UMLS | C4225309 |
| MedGen | 906476 |
| GARD | 0025010 |
| Is cancer (heuristic) | no |
Also known as: EBSND · epidermolysis bullosa simplex 5D, generalised intermediate, autosomal recessive · epidermolysis bullosa simplex 5D, generalized intermediate, autosomal recessive · epidermolysis bullosa simplex with nail dystrophy
Data availability: 5,755 ClinVar variants.
Disease family
Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › vesiculobullous skin disease › epidermolysis bullosa › inherited epidermolysis bullosa › epidermolysis bullosa simplex › epidermolysis bullosa simplex with nail dystrophy
Related subtypes (19): epidermolysis bullosa simplex 1A, generalized severe, epidermolysis bullosa simplex 1C, localized, epidermolysis bullosa simplex 1B, generalized intermediate, epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 2F, with mottled pigmentation, epidermolysis bullosa simplex 5B, with muscular dystrophy, epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive, epidermolysis bullosa simplex 7, with nephropathy and deafness, epidermolysis bullosa simplex 2E, with migratory circinate erythema, epidermolysis bullosa simplex 5C, with pyloric atresia, epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive, epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, suprabasal epidermolysis bullosa simplex, epidermolysis bullosa simplex with anodontia/hypodontia, epidermolysis bullosa simplex 2A, generalized severe, epidermolysis bullosa simplex 2B, generalized intermediate, epidermolysis bullosa simplex 2C, localized, epidermolysis bullosa simplex 2d, generalized, intermediate or severe, autosomal recessive
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
600 retrieved; paginated sample, class counts are floors:
300 uncertain significance, 221 likely benign, 34 benign, 22 conflicting classifications of pathogenicity, 13 benign/likely benign, 7 pathogenic, 3 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1069886 | NM_201384.3(PLEC):c.12418C>T (p.Arg4140Ter) | PLEC | Pathogenic | criteria provided, single submitter |
| 1071954 | NM_201384.3(PLEC):c.7336G>T (p.Glu2446Ter) | PLEC | Pathogenic | criteria provided, single submitter |
| 1073588 | NM_201384.3(PLEC):c.13106C>A (p.Ser4369Ter) | PLEC | Pathogenic | criteria provided, single submitter |
| 1074096 | NM_201384.3(PLEC):c.6510del (p.His2170fs) | PLEC | Pathogenic | criteria provided, single submitter |
| 1174482 | NM_201384.3(PLEC):c.864GCT[3] (p.Leu292del) | PLEC | Pathogenic | no assertion criteria provided |
| 1251951 | NM_201378.4(PLEC):c.66C>G (p.Tyr22Ter) | PLEC | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1251952 | NM_201384.3(PLEC):c.8149C>T (p.Gln2717Ter) | PLEC | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1320041 | NM_201384.3(PLEC):c.6970C>T (p.Arg2324Ter) | PLEC | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1323468 | NM_201384.3(PLEC):c.1465_1471del (p.Asn489fs) | PLEC | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1324937 | NM_201384.3(PLEC):c.4468C>T (p.Arg1490Ter) | PLEC | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1001872 | NM_201384.3(PLEC):c.7634G>A (p.Arg2545Gln) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1003332 | NM_201384.3(PLEC):c.6427G>A (p.Glu2143Lys) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1004138 | NM_201384.3(PLEC):c.9317G>A (p.Arg3106Lys) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1006392 | NM_201384.3(PLEC):c.8140G>A (p.Ala2714Thr) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1007882 | NM_201384.3(PLEC):c.5555C>T (p.Ala1852Val) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1038192 | NM_201384.3(PLEC):c.13529G>T (p.Gly4510Val) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1044930 | NM_201384.3(PLEC):c.8492G>A (p.Arg2831Gln) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1048028 | NM_201384.3(PLEC):c.3850C>T (p.Leu1284Phe) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1058015 | NM_201384.3(PLEC):c.9295G>A (p.Glu3099Lys) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1123939 | NM_201384.3(PLEC):c.9840C>T (p.Thr3280=) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1124265 | NM_201378.4(PLEC):c.70+2T>C | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1141659 | NM_201384.3(PLEC):c.5191C>T (p.Leu1731=) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1151961 | NM_201384.3(PLEC):c.5241G>A (p.Thr1747=) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1174478 | NM_201384.3(PLEC):c.8531C>T (p.Ala2844Val) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1194821 | NM_201384.3(PLEC):c.7703G>A (p.Arg2568His) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1195336 | NM_201384.3(PLEC):c.5920C>G (p.Gln1974Glu) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1215529 | NM_201384.3(PLEC):c.5795C>T (p.Ala1932Val) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1216951 | NM_201384.3(PLEC):c.3784G>A (p.Gly1262Ser) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 129930 | NM_201384.3(PLEC):c.12615C>T (p.Ile4205=) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 129932 | NM_000445.5(PLEC):c.133G>A (p.Gly45Ser) | PLEC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| RP1L1 | Orphanet:247834 | Occult macular dystrophy |
| RP1L1 | Orphanet:791 | Retinitis pigmentosa |
| FREM2 | Orphanet:2052 | Fraser syndrome |
| FREM2 | Orphanet:93100 | Renal agenesis, unilateral |
| FREM2 | Orphanet:98949 | Complete cryptophthalmia |
| IDS | Orphanet:217085 | Mucopolysaccharidosis type 2, severe form |
| IDS | Orphanet:217093 | Mucopolysaccharidosis type 2, attenuated form |
| PLEC | Orphanet:1114 | Aplasia cutis congenita |
| PLEC | Orphanet:158684 | Epidermolysis bullosa simplex with pyloric atresia |
| PLEC | Orphanet:254361 | Plectin-related limb-girdle muscular dystrophy R17 |
| PLEC | Orphanet:257 | Epidermolysis bullosa simplex with muscular dystrophy |
| PLEC | Orphanet:79401 | PLEC-related intermediate epidermolysis bullosa simplex without extracutaneous involvement |
Cohort genes → proteins
13 cohort genes, 11 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 13 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| RP1L1 | HGNC:15946 | ENSG00000183638 | Q8IWN7 | Retinitis pigmentosa 1-like 1 protein | clinvar |
| BCLAF1 | HGNC:16863 | ENSG00000029363 | Q9NYF8 | Bcl-2-associated transcription factor 1 | clinvar |
| DCUN1D2 | HGNC:20328 | ENSG00000150401 | Q6PH85 | DCN1-like protein 2 | clinvar |
| ADCK5 | HGNC:21738 | ENSG00000173137 | Q3MIX3 | Uncharacterized aarF domain-containing protein kinase 5 | clinvar |
| ARHGAP21 | HGNC:23725 | ENSG00000107863 | Q5T5U3 | Rho GTPase-activating protein 21 | clinvar |
| FREM2 | HGNC:25396 | ENSG00000150893 | Q5SZK8 | FRAS1-related extracellular matrix protein 2 | clinvar |
| ARHGAP10 | HGNC:26099 | ENSG00000071205 | A1A4S6 | Rho GTPase-activating protein 10 | clinvar |
| MIR661 | HGNC:32917 | ENSG00000207574 | microRNA 661 | clinvar | |
| CATSPERQ | HGNC:44155 | ENSG00000261587 | Q2WGJ8 | Cation channel sperm-associated auxiliary subunit theta | clinvar |
| GPR33 | HGNC:4489 | ENSG00000214943 | Q49SQ1 | Probable G-protein coupled receptor 33 | clinvar |
| IDS | HGNC:5389 | ENSG00000010404 | P22304 | Iduronate 2-sulfatase | clinvar |
| CCDST | HGNC:55988 | ENSG00000236427 | cervical cancer associated DHX9 suppressive transcript | clinvar | |
| PLEC | HGNC:9069 | ENSG00000178209 | Q15149 | Plectin | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| RP1L1 | Retinitis pigmentosa 1-like 1 protein | Required for the differentiation of photoreceptor cells. |
| BCLAF1 | Bcl-2-associated transcription factor 1 | Death-promoting transcriptional repressor. |
| DCUN1D2 | DCN1-like protein 2 | Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes and plays an essential role in the regulation of SCF (SKP1-CU… |
| ADCK5 | Uncharacterized aarF domain-containing protein kinase 5 | The function of this protein is not yet clear. |
| ARHGAP21 | Rho GTPase-activating protein 21 | Functions as a GTPase-activating protein (GAP) for RHOA and CDC42. |
| FREM2 | FRAS1-related extracellular matrix protein 2 | Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia. |
| ARHGAP10 | Rho GTPase-activating protein 10 | GTPase-activating protein that catalyzes the conversion of active GTP-bound Rho GTPases to their inactive GDP-bound form, thus suppressing various Rho GTPase-mediated cellular processes. |
| CATSPERQ | Cation channel sperm-associated auxiliary subunit theta | Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation. |
| GPR33 | Probable G-protein coupled receptor 33 | Orphan receptor; could be a chemoattractant receptor. |
| IDS | Iduronate 2-sulfatase | Lysosomal enzyme involved in the degradation pathway of dermatan sulfate and heparan sulfate. |
| PLEC | Plectin | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. |
Protein-family classification
Druggable: 3 · Difficult: 3 · Unknown: 7 · Druggable fraction: 0.23
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 | 3 | 4.0× | 0.178 |
| Phosphatase | 1 | 6.5× | 0.361 |
| Kinase | 1 | 2.1× | 0.532 |
| GPCR | 1 | 1.8× | 0.532 |
| Other/Unknown | 7 | 1.0× | 0.666 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| RP1L1 | Other/Unknown | no | Doublecortin_dom, Doublecortin_dom_sf | |
| BCLAF1 | Other/Unknown | no | THRAP3_BCLAF1 | |
| DCUN1D2 | Other/Unknown | no | PONY_dom, UBA-like_sf, DCN-prot | |
| ADCK5 | Kinase | yes | ABC1_dom, Kinase-like_dom_sf, ADCK1_dom | |
| ARHGAP21 | Scaffold/PPI | no | RhoGAP_dom, PDZ, PH_domain | |
| FREM2 | Other/Unknown | no | Calx_beta, CalX-like_sf, CSPG_rpt | |
| ARHGAP10 | Scaffold/PPI | no | RhoGAP_dom, SH3_domain, PH_domain | |
| MIR661 | Other/Unknown | no | ||
| CATSPERQ | Other/Unknown | no | TMEM249 | |
| GPR33 | GPCR | yes | GPCR_Rhodpsn, Formyl_rcpt-rel, GPCR_Rhodpsn_7TM | |
| IDS | Phosphatase | yes | 3.1.6.13 | Sulfatase_N, Alkaline_phosphatase_core_sf, Sulfatase_CS |
| CCDST | Other/Unknown | no | ||
| PLEC | Scaffold/PPI | no | Plectin_repeat, SH3_domain, Actinin_actin-bd_CS |
Expression context
Cohort genes with no expression data: 0.
8 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) | 1 |
| broad (>20) | 12 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| duodenum | 2 |
| right hemisphere of cerebellum | 2 |
| adrenal tissue | 2 |
| male germ line stem cell (sensu Vertebrata) in testis | 2 |
| bone marrow cell | 1 |
| buccal mucosa cell | 1 |
| primordial germ cell in gonad | 1 |
| calcaneal tendon | 1 |
| embryo | 1 |
| tibia | 1 |
| apex of heart | 1 |
| cardiac ventricle | 1 |
| heart left ventricle | 1 |
| mucosa of transverse colon | 1 |
| cerebellar cortex | 1 |
| cerebellar hemisphere | 1 |
| kidney epithelium | 1 |
| renal medulla | 1 |
| lower esophagus | 1 |
| lower esophagus muscularis layer | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| RP1L1 | 30 | tissue_specific | yes | primordial germ cell in gonad, buccal mucosa cell, bone marrow cell |
| BCLAF1 | 295 | ubiquitous | marker | calcaneal tendon, tibia, embryo |
| DCUN1D2 | 270 | ubiquitous | marker | apex of heart, heart left ventricle, cardiac ventricle |
| ADCK5 | 136 | ubiquitous | marker | mucosa of transverse colon, duodenum, right hemisphere of cerebellum |
| ARHGAP21 | 225 | ubiquitous | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
| FREM2 | 160 | broad | marker | adrenal tissue, kidney epithelium, renal medulla |
| ARHGAP10 | 202 | ubiquitous | marker | mucosa of stomach, lower esophagus muscularis layer, lower esophagus |
| MIR661 | 89 | yes | adrenal tissue, vermiform appendix, blood | |
| CATSPERQ | 123 | tissue_specific | yes | right testis, left testis, male germ line stem cell (sensu Vertebrata) in testis |
| GPR33 | 10 | tissue_specific | yes | duodenum, leukocyte, colonic epithelium |
| IDS | 238 | ubiquitous | marker | right frontal lobe, cortical plate, descending thoracic aorta |
| CCDST | 111 | broad | yes | male germ line stem cell (sensu Vertebrata) in testis, lower esophagus mucosa, quadriceps femoris |
| PLEC | 283 | ubiquitous | marker | sural nerve, hindlimb stylopod muscle, tibial nerve |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| BCLAF1 | 4,230 |
| PLEC | 3,529 |
| ARHGAP21 | 1,768 |
| FREM2 | 1,652 |
| IDS | 1,123 |
| RP1L1 | 1,004 |
| ADCK5 | 978 |
| DCUN1D2 | 612 |
| ARHGAP10 | 493 |
| GPR33 | 394 |
Structural data
PDB: 6 · AlphaFold-only: 5 · No structure: 2
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| PLEC | Q15149 | 14 |
| ARHGAP21 | Q5T5U3 | 3 |
| BCLAF1 | Q9NYF8 | 2 |
| IDS | P22304 | 2 |
| DCUN1D2 | Q6PH85 | 1 |
| ARHGAP10 | A1A4S6 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| GPR33 | Q49SQ1 | 87.59 |
| ADCK5 | Q3MIX3 | 82.08 |
| CATSPERQ | Q2WGJ8 | 79.42 |
| RP1L1 | Q8IWN7 | 38.97 |
| FREM2 | Q5SZK8 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 13 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| MPS II - Hunter syndrome (HS-GAG degradation) | 1 | 2284.0× | 0.005 | IDS |
| MPS II - Hunter syndrome (CS/DS degradation) | 1 | 2284.0× | 0.005 | IDS |
| Regulation of PAK-2p34 activity by PS-GAP/RHG10 | 1 | 1142.0× | 0.006 | ARHGAP10 |
| RHOA GTPase cycle | 2 | 29.9× | 0.008 | ARHGAP21, ARHGAP10 |
| CDC42 GTPase cycle | 2 | 28.9× | 0.008 | ARHGAP21, ARHGAP10 |
| RAC1 GTPase cycle | 2 | 24.4× | 0.009 | ARHGAP21, ARHGAP10 |
| Type I hemidesmosome assembly | 1 | 207.6× | 0.014 | PLEC |
| Caspase-mediated cleavage of cytoskeletal proteins | 1 | 190.3× | 0.014 | PLEC |
| CS/DS degradation | 1 | 108.8× | 0.022 | IDS |
| HS-GAG degradation | 1 | 99.3× | 0.022 | IDS |
| RHOF GTPase cycle | 1 | 51.9× | 0.035 | ARHGAP21 |
| RND3 GTPase cycle | 1 | 51.9× | 0.035 | ARHGAP21 |
| RHOD GTPase cycle | 1 | 40.8× | 0.036 | ARHGAP21 |
| Assembly of collagen fibrils and other multimeric structures | 1 | 40.1× | 0.036 | PLEC |
| RHOJ GTPase cycle | 1 | 40.1× | 0.036 | ARHGAP21 |
| RHOQ GTPase cycle | 1 | 36.2× | 0.038 | ARHGAP21 |
| RHOB GTPase cycle | 1 | 30.9× | 0.039 | ARHGAP21 |
| RHOG GTPase cycle | 1 | 29.7× | 0.039 | ARHGAP21 |
| RHOC GTPase cycle | 1 | 29.3× | 0.039 | ARHGAP21 |
| RAC2 GTPase cycle | 1 | 25.4× | 0.043 | ARHGAP21 |
| RAC3 GTPase cycle | 1 | 23.8× | 0.043 | ARHGAP21 |
| Neddylation | 1 | 9.5× | 0.101 | DCUN1D2 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| protein-containing complex organization | 1 | 1872.4× | 0.018 | PLEC |
| actomyosin contractile ring assembly actin filament organization | 1 | 1872.4× | 0.018 | PLEC |
| skeletal myofibril assembly | 1 | 936.2× | 0.018 | PLEC |
| leukocyte migration involved in immune response | 1 | 624.1× | 0.018 | PLEC |
| cellular response to hydrostatic pressure | 1 | 624.1× | 0.018 | PLEC |
| dermatan sulfate proteoglycan catabolic process | 1 | 468.1× | 0.018 | IDS |
| photoreceptor cell development | 1 | 468.1× | 0.018 | RP1L1 |
| maintenance of Golgi location | 1 | 468.1× | 0.018 | ARHGAP21 |
| regulation of small GTPase mediated signal transduction | 2 | 32.0× | 0.018 | ARHGAP21, ARHGAP10 |
| tight junction organization | 1 | 374.5× | 0.018 | PLEC |
| positive regulation of protein neddylation | 1 | 374.5× | 0.018 | DCUN1D2 |
| glycosaminoglycan catabolic process | 1 | 267.5× | 0.021 | IDS |
| hemidesmosome assembly | 1 | 267.5× | 0.021 | PLEC |
| Golgi localization | 1 | 234.1× | 0.021 | ARHGAP21 |
| heparan sulfate proteoglycan catabolic process | 1 | 208.1× | 0.021 | IDS |
| establishment of Golgi localization | 1 | 208.1× | 0.021 | ARHGAP21 |
| positive regulation of DNA-templated transcription initiation | 1 | 208.1× | 0.021 | BCLAF1 |
| keratinocyte development | 1 | 170.2× | 0.023 | PLEC |
| peripheral nervous system myelin maintenance | 1 | 170.2× | 0.023 | PLEC |
| cellular response to fluid shear stress | 1 | 144.0× | 0.025 | PLEC |
| organelle transport along microtubule | 1 | 133.8× | 0.025 | ARHGAP21 |
| complement receptor mediated signaling pathway | 1 | 124.8× | 0.025 | GPR33 |
| T cell chemotaxis | 1 | 124.8× | 0.025 | PLEC |
| regulation of vascular permeability | 1 | 124.8× | 0.025 | PLEC |
| photoreceptor cell outer segment organization | 1 | 117.0× | 0.026 | RP1L1 |
| intermediate filament cytoskeleton organization | 1 | 104.0× | 0.026 | PLEC |
| regulation of protein neddylation | 1 | 104.0× | 0.026 | DCUN1D2 |
| cell communication | 1 | 93.6× | 0.026 | FREM2 |
| fibroblast migration | 1 | 93.6× | 0.026 | PLEC |
| respiratory electron transport chain | 1 | 93.6× | 0.026 | PLEC |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 11
Druggability breadth: 4 of 13 evidence-associated genes (31%) 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 |
|---|---|
| ADCK5 | NERATINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| ADCK5 | 2 | 4 |
| BCLAF1 | 1 | 2 |
| RP1L1 | 0 | 0 |
| DCUN1D2 | 0 | 0 |
| ARHGAP21 | 0 | 0 |
| FREM2 | 0 | 0 |
| ARHGAP10 | 0 | 0 |
| MIR661 | 0 | 0 |
| CATSPERQ | 0 | 0 |
| GPR33 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| NERATINIB | 4 | ADCK5 |
| LINSITINIB | 3 | ADCK5 |
| MOLIBRESIB | 2 | BCLAF1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PLEC | 12 | Binding:12 |
| BCLAF1 | 8 | Binding:8 |
| DCUN1D2 | 5 | Binding:5 |
| ADCK5 | 2 | Binding:2 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| IDS | 3.1.6.13 | iduronate-2-sulfatase |
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
3 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) |
|---|---|---|
| NERATINIB | 4 | ADCK5 |
| LINSITINIB | 3 | ADCK5 |
| MOLIBRESIB | 2 | BCLAF1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | ADCK5 |
| B | Phased (≥1) drug, not yet approved | 1 | BCLAF1 |
| C | Druggable family + PDB, no drug | 1 | IDS |
| D | Druggable family + AlphaFold only, no drug | 1 | GPR33 |
| E | Difficult family or no structure, no drug | 9 | RP1L1, DCUN1D2, ARHGAP21, FREM2, ARHGAP10, MIR661, CATSPERQ, CCDST, PLEC |
Undrugged target profiles
11 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| RP1L1 | 0 | — |
| DCUN1D2 | 5 | — |
| ARHGAP21 | 0 | — |
| FREM2 | 0 | — |
| ARHGAP10 | 0 | — |
| MIR661 | 0 | — |
| CATSPERQ | 0 | — |
| GPR33 | 0 | — |
| IDS | 0 | — |
| CCDST | 0 | — |
| PLEC | 12 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.