Ehlers-Danlos syndrome, kyphoscoliotic type 1
disease diseaseOn this page
Also known as EDS 6EDS 6 (formerly)EDS VIEDS VIAEDS, kyphoscoliotic typeEDS, oculoscoliotic typeEDS6EDS6A, formerlyEDSKSCL1Ehlers-Danlos syndrome kyphoscoliotic typeEhlers-Danlos syndrome oculoscoliotic typeEhlers-Danlos syndrome type 6 (formerly)Ehlers-Danlos syndrome type 6AEhlers-Danlos syndrome type 6A (formerly)Ehlers-Danlos syndrome, kyphoscoliosis typeEhlers-Danlos syndrome, kyphoscoliotic typeEhlers-Danlos syndrome, ocular-scoliotic typeEhlers-Danlos syndrome, oculoscoliotic typeEhlers-Danlos syndrome, type 6
Summary
Ehlers-Danlos syndrome, kyphoscoliotic type 1 (MONDO:0016002) is a disease caused by PLOD1 (GenCC Definitive), with 4 cohort genes.
At a glance
- Prevalence: Unknown (Worldwide)
- Causal gene: PLOD1 (GenCC Definitive)
- Cohort genes: 4
- ClinVar variants: 1,030
- Phenotypes (HPO): 66
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Prevalence at birth | 1-9 / 100 000 | 1 | Worldwide | Not yet validated |
Signs & symptoms
Clinical features (HPO)
66 HPO clinical features (Orphanet curated; top 50 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000938 | Osteopenia | Very frequent (80-99%) |
| HP:0000939 | Osteoporosis | Very frequent (80-99%) |
| HP:0000974 | Hyperextensible skin | Very frequent (80-99%) |
| HP:0000978 | Bruising susceptibility | Very frequent (80-99%) |
| HP:0000987 | Atypical scarring of skin | Very frequent (80-99%) |
| HP:0001030 | Fragile skin | Very frequent (80-99%) |
| HP:0001252 | Hypotonia | Very frequent (80-99%) |
| HP:0001319 | Neonatal hypotonia | Very frequent (80-99%) |
| HP:0005659 | Thoracic kyphoscoliosis | Very frequent (80-99%) |
| HP:0012379 | Abnormal enzyme/coenzyme activity | Very frequent (80-99%) |
| HP:0001382 | Joint hypermobility | Very frequent (80-99%) |
| HP:0000482 | Microcornea | Frequent (30-79%) |
| HP:0001075 | Atrophic scars | Frequent (30-79%) |
| HP:0001324 | Muscle weakness | Frequent (30-79%) |
| HP:0001373 | Joint dislocation | Frequent (30-79%) |
| HP:0001519 | Disproportionate tall stature | Frequent (30-79%) |
| HP:0001762 | Talipes equinovarus | Frequent (30-79%) |
| HP:0002761 | Generalized joint laxity | Frequent (30-79%) |
| HP:0002827 | Hip dislocation | Frequent (30-79%) |
| HP:0002943 | Thoracic scoliosis | Frequent (30-79%) |
| HP:0032153 | Joint subluxation | Frequent (30-79%) |
| HP:0000023 | Inguinal hernia | Occasional (5-29%) |
| HP:0000501 | Glaucoma | Occasional (5-29%) |
| HP:0000540 | Hypermetropia | Occasional (5-29%) |
| HP:0000541 | Retinal detachment | Occasional (5-29%) |
| HP:0000545 | Myopia | Occasional (5-29%) |
| HP:0000592 | Blue sclerae | Occasional (5-29%) |
| HP:0000767 | Pectus excavatum | Occasional (5-29%) |
| HP:0001058 | Poor wound healing | Occasional (5-29%) |
| HP:0001315 | Reduced tendon reflexes | Occasional (5-29%) |
| HP:0001537 | Umbilical hernia | Occasional (5-29%) |
| HP:0001634 | Mitral valve prolapse | Occasional (5-29%) |
| HP:0001892 | Abnormal bleeding | Occasional (5-29%) |
| HP:0002194 | Delayed gross motor development | Occasional (5-29%) |
| HP:0002495 | Impaired vibratory sensation | Occasional (5-29%) |
| HP:0002617 | Dilatation | Occasional (5-29%) |
| HP:0002647 | Aortic dissection | Occasional (5-29%) |
| HP:0002999 | Patellar dislocation | Occasional (5-29%) |
| HP:0003199 | Decreased muscle mass | Occasional (5-29%) |
| HP:0003324 | Generalized muscle weakness | Occasional (5-29%) |
| HP:0003458 | EMG: myopathic abnormalities | Occasional (5-29%) |
| HP:0003690 | Limb muscle weakness | Occasional (5-29%) |
| HP:0003835 | Shoulder subluxation | Occasional (5-29%) |
| HP:0004942 | Aortic aneurysm | Occasional (5-29%) |
| HP:0005294 | Arterial dissection | Occasional (5-29%) |
| HP:0008780 | Congenital bilateral hip dislocation | Occasional (5-29%) |
| HP:0020152 | Distal joint laxity | Occasional (5-29%) |
| HP:0025019 | Arterial rupture | Occasional (5-29%) |
| HP:0025513 | Scleral rupture | Occasional (5-29%) |
| HP:0030043 | Hip subluxation | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Ehlers-Danlos syndrome, kyphoscoliotic type 1 |
| Mondo ID | MONDO:0016002 |
| MeSH | C536198 |
| OMIM | 225400 |
| Orphanet | 1900 |
| DOID | DOID:0080734 |
| NCIT | C125700 |
| SNOMED CT | 718211004 |
| UMLS | C0268342 |
| MedGen | 75672 |
| GARD | 0022216 |
| Is cancer (heuristic) | no |
Also known as: EDS 6 · EDS 6 (formerly) · EDS VI · EDS VIA · EDS, kyphoscoliotic type · EDS, oculoscoliotic type · EDS6 · EDS6A, formerly · EDSKSCL1 · Ehlers-Danlos syndrome kyphoscoliotic type · Ehlers-Danlos syndrome oculoscoliotic type · Ehlers-Danlos syndrome type 6 (formerly) · Ehlers-Danlos syndrome type 6A · Ehlers-Danlos syndrome type 6A (formerly) · Ehlers-Danlos syndrome, kyphoscoliosis type · Ehlers-Danlos syndrome, kyphoscoliotic type · Ehlers-Danlos syndrome, kyphoscoliotic type 1 · Ehlers-Danlos syndrome, ocular-scoliotic type · Ehlers-Danlos syndrome, oculoscoliotic type · Ehlers-Danlos syndrome, type 6 (+11 more)
Data availability: 1,030 ClinVar variants · 5 GenCC gene-disease records · 7 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › Ehlers-Danlos syndrome, kyphoscoliotic type 1
Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia
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:
346 likely benign, 141 uncertain significance, 34 pathogenic, 28 conflicting classifications of pathogenicity, 21 likely pathogenic, 11 benign/likely benign, 10 benign, 9 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1070287 | NM_000302.4(PLOD1):c.367C>T (p.Gln123Ter) | PLOD1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1073871 | NM_000302.4(PLOD1):c.145C>T (p.Gln49Ter) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 1377914 | NM_000302.4(PLOD1):c.467-2del | PLOD1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1404450 | NM_000302.4(PLOD1):c.2025C>G (p.Tyr675Ter) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 1413244 | NC_000001.10:g.(?12020683)(12027168_?)dup | PLOD1 | Pathogenic | criteria provided, single submitter |
| 14364 | NM_000302.4(PLOD1):c.955C>T (p.Arg319Ter) | PLOD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14365 | NC_000001.11:g.(11959822_11959973)_(11968469_11968718)dup | PLOD1 | Pathogenic | no assertion criteria provided |
| 14366 | NM_000302.4(PLOD1):c.2032G>A (p.Gly678Arg) | PLOD1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14368 | NM_000302.4(PLOD1):c.1651-2del | PLOD1 | Pathogenic | no assertion criteria provided |
| 14369 | NM_000302.3(PLOD1):c.1756_1902del | PLOD1 | Pathogenic | no assertion criteria provided |
| 14370 | NM_000302.4(PLOD1):c.1533C>G (p.Tyr511Ter) | PLOD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14371 | NM_000302.4(PLOD1):c.579+1G>A | PLOD1 | Pathogenic | criteria provided, single submitter |
| 14372 | NM_000302.4(PLOD1):c.1836G>C (p.Trp612Cys) | PLOD1 | Pathogenic | no assertion criteria provided |
| 14373 | NM_000302.4(PLOD1):c.2008C>T (p.Arg670Ter) | PLOD1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1452011 | NM_000302.4(PLOD1):c.1170_1192del (p.Asn391fs) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 1454300 | NM_000302.4(PLOD1):c.1646del (p.Glu549fs) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 1455652 | NM_000302.4(PLOD1):c.272del (p.Lys91fs) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 1460062 | NC_000001.10:g.(?12014867)(12014970_?)del | PLOD1 | Pathogenic | criteria provided, single submitter |
| 1980006 | NM_000302.4(PLOD1):c.331del (p.Arg111fs) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 2089294 | NM_000302.4(PLOD1):c.1711G>T (p.Glu571Ter) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 2108622 | NM_000302.4(PLOD1):c.1365C>G (p.Tyr455Ter) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 2111795 | NM_000302.4(PLOD1):c.1813C>T (p.Gln605Ter) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 2413497 | NM_000302.4(PLOD1):c.1261dup (p.Ala421fs) | PLOD1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2422835 | NC_000001.10:g.(?12008013)(12008144_?)del | PLOD1 | Pathogenic | criteria provided, single submitter |
| 264119 | NM_000302.4(PLOD1):c.404_423del (p.Asp135fs) | PLOD1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 265507 | NM_000302.4(PLOD1):c.1651-2A>G | PLOD1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2702181 | NM_000302.4(PLOD1):c.1698T>A (p.Cys566Ter) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 2733827 | NM_000302.4(PLOD1):c.153dup (p.Asn52fs) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 2735026 | NM_000302.4(PLOD1):c.180del (p.Glu62fs) | PLOD1 | Pathogenic | criteria provided, single submitter |
| 2750647 | NM_000302.4(PLOD1):c.274G>T (p.Glu92Ter) | PLOD1 | Pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · 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 |
|---|---|---|---|---|
| PLOD1 | Definitive | Autosomal recessive | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PLOD1 | Orphanet:1900 | Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency |
| DCLRE1C | Orphanet:275 | Severe combined immunodeficiency due to DCLRE1C deficiency |
| DCLRE1C | Orphanet:39041 | Omenn syndrome |
| CLCN6 | Orphanet:610573 | CLCN6-related childhood-onset progressive neurodegeneration-peripheral neuropathy syndrome |
| ABCD1 | Orphanet:139396 | X-linked cerebral adrenoleukodystrophy |
| ABCD1 | Orphanet:139399 | Adrenomyeloneuropathy |
| ABCD1 | Orphanet:369942 | CADDS |
| ABCD1 | Orphanet:388 | Hirschsprung disease |
Cohort genes → proteins
4 cohort genes, 4 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 4 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| PLOD1 | HGNC:9081 | ENSG00000083444 | Q02809 | Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 | gencc,clinvar |
| DCLRE1C | HGNC:17642 | ENSG00000152457 | Q96SD1 | Protein artemis | clinvar |
| CLCN6 | HGNC:2024 | ENSG00000011021 | P51797 | H(+)/Cl(-) exchange transporter 6 | clinvar |
| ABCD1 | HGNC:61 | ENSG00000101986 | P33897 | ATP-binding cassette sub-family D member 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| 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. |
| DCLRE1C | Protein artemis | Nuclease involved in DNA non-homologous end joining (NHEJ); required for double-strand break repair and V(D)J recombination. |
| CLCN6 | H(+)/Cl(-) exchange transporter 6 | Voltage-gated channel mediating the exchange of chloride ions against protons. |
| ABCD1 | ATP-binding cassette sub-family D member 1 | ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.25
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 |
|---|---|---|---|
| Transporter | 1 | 19.4× | 0.101 |
| Other/Unknown | 3 | 1.3× | 0.404 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PLOD1 | Other/Unknown | no | Procol_lys_dOase, Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph | |
| DCLRE1C | Other/Unknown | no | DRMBL, RibonucZ/Hydroxyglut_hydro | |
| CLCN6 | Other/Unknown | no | CBS_dom, ClC, Cl_channel-6 | |
| ABCD1 | Transporter | yes | 7.6.2.4 | ABC_transporter-like_ATP-bd, AAA+_ATPase, FA_transporter |
Expression context
Cohort genes with no expression data: 0.
4 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) | 4 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| apex of heart | 1 |
| smooth muscle tissue | 1 |
| stromal cell of endometrium | 1 |
| buccal mucosa cell | 1 |
| epithelium of nasopharynx | 1 |
| tendon of biceps brachii | 1 |
| left testis | 1 |
| right atrium auricular region | 1 |
| right testis | 1 |
| ileal mucosa | 1 |
| left adrenal gland | 1 |
| left adrenal gland cortex | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PLOD1 | 279 | ubiquitous | marker | stromal cell of endometrium, smooth muscle tissue, apex of heart |
| DCLRE1C | 284 | ubiquitous | marker | buccal mucosa cell, tendon of biceps brachii, epithelium of nasopharynx |
| CLCN6 | 239 | ubiquitous | marker | right testis, left testis, right atrium auricular region |
| ABCD1 | 201 | ubiquitous | marker | ileal mucosa, left adrenal gland cortex, left adrenal gland |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PLOD1 | 1,929 |
| DCLRE1C | 1,756 |
| ABCD1 | 1,181 |
| CLCN6 | 1,042 |
Structural data
PDB: 3 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| DCLRE1C | Q96SD1 | 14 |
| ABCD1 | P33897 | 14 |
| CLCN6 | P51797 | 3 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| PLOD1 | Q02809 | 93.04 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 21. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Defective ABCD1 causes ALD | 1 | 1427.5× | 0.015 | ABCD1 |
| alpha-linolenic (omega3) and linoleic (omega6) acid metabolism | 1 | 475.8× | 0.020 | ABCD1 |
| Linoleic acid (LA) metabolism | 1 | 285.5× | 0.020 | ABCD1 |
| Beta-oxidation of very long chain fatty acids | 1 | 219.6× | 0.020 | ABCD1 |
| alpha-linolenic acid (ALA) metabolism | 1 | 178.4× | 0.020 | ABCD1 |
| Peroxisomal lipid metabolism | 1 | 167.9× | 0.020 | ABCD1 |
| ABC transporters in lipid homeostasis | 1 | 150.3× | 0.020 | ABCD1 |
| Class I peroxisomal membrane protein import | 1 | 129.8× | 0.020 | ABCD1 |
| ABC transporter disorders | 1 | 109.8× | 0.021 | ABCD1 |
| Protein localization | 1 | 47.6× | 0.038 | ABCD1 |
| Collagen biosynthesis and modifying enzymes | 1 | 42.6× | 0.038 | PLOD1 |
| Signaling by BRAF and RAF1 fusions | 1 | 42.6× | 0.038 | CLCN6 |
| Nonhomologous End-Joining (NHEJ) | 1 | 42.0× | 0.038 | DCLRE1C |
| Disorders of transmembrane transporters | 1 | 34.8× | 0.040 | ABCD1 |
| Stimuli-sensing channels | 1 | 34.0× | 0.040 | CLCN6 |
| Fatty acid metabolism | 1 | 32.8× | 0.040 | ABCD1 |
| ABC-family protein mediated transport | 1 | 30.4× | 0.040 | ABCD1 |
| Metabolism of lipids | 1 | 7.9× | 0.141 | ABCD1 |
| Transport of small molecules | 1 | 6.3× | 0.166 | ABCD1 |
| Disease | 1 | 3.3× | 0.286 | ABCD1 |
| Metabolism | 1 | 2.9× | 0.302 | ABCD1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| peroxisomal membrane transport | 1 | 2106.5× | 0.006 | ABCD1 |
| very long-chain fatty-acyl-CoA catabolic process | 1 | 2106.5× | 0.006 | ABCD1 |
| obsolete hydroxylysine biosynthetic process | 1 | 1404.3× | 0.006 | PLOD1 |
| positive regulation of unsaturated fatty acid biosynthetic process | 1 | 1404.3× | 0.006 | ABCD1 |
| sterol homeostasis | 1 | 1053.2× | 0.006 | ABCD1 |
| long-chain fatty acid import into peroxisome | 1 | 842.6× | 0.006 | ABCD1 |
| regulation of fatty acid beta-oxidation | 1 | 702.2× | 0.006 | ABCD1 |
| long-chain fatty acid catabolic process | 1 | 702.2× | 0.006 | ABCD1 |
| myelin maintenance | 1 | 702.2× | 0.006 | ABCD1 |
| regulation of mitochondrial depolarization | 1 | 702.2× | 0.006 | ABCD1 |
| fatty acid elongation | 1 | 601.9× | 0.006 | ABCD1 |
| very long-chain fatty acid catabolic process | 1 | 601.9× | 0.006 | ABCD1 |
| V(D)J recombination | 1 | 526.6× | 0.006 | DCLRE1C |
| positive regulation of fatty acid beta-oxidation | 1 | 383.0× | 0.007 | ABCD1 |
| fatty acid derivative biosynthetic process | 1 | 383.0× | 0.007 | ABCD1 |
| regulation of cellular response to oxidative stress | 1 | 324.1× | 0.008 | ABCD1 |
| regulation of oxidative phosphorylation | 1 | 300.9× | 0.008 | ABCD1 |
| neuron projection maintenance | 1 | 280.9× | 0.008 | ABCD1 |
| collagen biosynthetic process | 1 | 263.3× | 0.009 | PLOD1 |
| negative regulation of reactive oxygen species biosynthetic process | 1 | 247.8× | 0.009 | ABCD1 |
| fatty acid homeostasis | 1 | 234.1× | 0.009 | ABCD1 |
| alpha-linolenic acid metabolic process | 1 | 221.7× | 0.009 | ABCD1 |
| peroxisome organization | 1 | 200.6× | 0.009 | ABCD1 |
| very long-chain fatty acid metabolic process | 1 | 191.5× | 0.009 | ABCD1 |
| linoleic acid metabolic process | 1 | 175.5× | 0.010 | ABCD1 |
| unsaturated fatty acid biosynthetic process | 1 | 162.0× | 0.010 | ABCD1 |
| cell volume homeostasis | 1 | 150.5× | 0.011 | CLCN6 |
| chloride transport | 1 | 113.9× | 0.013 | CLCN6 |
| long-chain fatty acid biosynthetic process | 1 | 110.9× | 0.013 | ABCD1 |
| interstrand cross-link repair | 1 | 108.0× | 0.013 | DCLRE1C |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 4
Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| PLOD1 | 0 | 0 |
| DCLRE1C | 0 | 0 |
| CLCN6 | 0 | 0 |
| ABCD1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PLOD1 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| ABCD1 | 7.6.2.4 | ABC-type fatty-acyl-CoA transporter |
Pharmacogenomics
Cohort genes with a PharmGKB record: 4; 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 | ABCD1 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 3 | PLOD1, DCLRE1C, CLCN6 |
Undrugged target profiles
4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| PLOD1 | 1 | — |
| DCLRE1C | 0 | — |
| CLCN6 | 0 | — |
| ABCD1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.