WBM coverage of the IMDs
For every inherited metabolic disease (IMD) in the catalogue, is its causal gene present in a whole-body-model (WBM) reaction? A disease is WBM-covered when its gene appears in a WBM reaction GPR (the four reference models 3/4/187/188). Of the 2350 IMDs with a known causal gene, 1047 (45%) are covered — the other 1303 are the real modelling gap. (1047/2607 = 40% of all IMDs, but 257 have no recorded causal gene, so they can never be in a WBM.)
Coverage means the gene is in the model — not that the model reproduces the disease phenotype (that is a stronger, flux-level claim). Live view of the current database. Research & education over a public knowledge base — not clinical, diagnostic, or individual guidance.
What the 2,607 IMDs are
The IMD universe is every reconws_diseases row tagged diseaseType = 'Inherited metabolic disease' — the ICIMD / IEMbase inherited-metabolic-disease nosology (ICIMD is the classification built on IEMbase's IEM#### codes), cross-referenced to OMIM and Orphanet. These identifiers overlap (a disease can carry all three), so the rows below do not partition the set and should not be summed.
| Identifier | IMDs with it | What it is |
|---|---|---|
| IEM code (IEMbase / ICIMD) | 2,331 | The inherited-metabolic-disease nosology code (1,902 distinct; some codes span several subtype rows) |
| OMIM | 2,334 | Online Mendelian Inheritance in Man disease id |
| Orphanet | 1,248 | Orphanet rare-disease id |
| Total rows | 2,607 | Distinct IMD rows (the denominator on this page); 276 carry no IEM code |
Note on diseaseSource: the source label (ICIMD 2,273, IEMBASE 334) records which import created each row, not which knowledge base the disease belongs to — so it is not "only 334 IEMbase diseases." 2,331 of the 2,607 IMDs carry an IEM code, spread across both labels. If a disease is re-curated in or out of the nosology the denominator follows (this page is live).
The gap: recon-backfill vs missing
The 1,303 IMDs whose gene is not in the WBMs split into two very different kinds of gap. Filter the table below to gap and sort by the Gap type column to work the list.
Flux-level coverage (note): all 1,047 covered genes have at least one WBM reaction whose bounds allow flux, so none are structurally trapped behind blocked-only reactions. But bounds open ≠ phenotype reproduced — a true flux-level claim needs a flux-balance solve per disease. See the biomarker prediction analysis for the WBM's actual predictive behaviour.
IMDs vs other diseases
The WBM is a metabolic model, so it covers inherited metabolic diseases far more densely than the other diseases in the catalogue (OMIM / ORPHA / MONDO and gene-association entries), most of which are non-metabolic.
| Gene in a WBM | of all | of gene-bearing | |
|---|---|---|---|
| IMDs | 1,047 / 2,607 | 40% | 45% |
| Other diseases | 600 / 10,690 | 6% | 21% |
Coverage by ICIMD category
Where the WBM is strong and weak, by top-level ICIMD nosology category. Coverage is over the gene-bearing IMDs in each category (bar), sorted by number covered.
| ICIMD category | IMDs | Gene in WBM | of gene-bearing |
|---|---|---|---|
| Disorders of lipid metabolism | 185 | 139/184 | 76% |
| Disorders of amino acid metabolism | 156 | 135/149 | 91% |
| No ICIMD category | 446 | 98/207 | 47% |
| Congenital disorders of glycosylation | 171 | 95/171 | 56% |
| Disorders of carbohydrate metabolism | 103 | 82/101 | 81% |
| Disorders of nucleobase, nucleotide and nucleic acid metabolism | 196 | 59/195 | 30% |
| Disorders of complex molecule degradation | 114 | 59/114 | 52% |
| Nuclear-encoded disorders of oxidative phosphorylation | 98 | 52/98 | 53% |
| Disorders of vitamin and cofactor metabolism | 96 | 52/96 | 54% |
| Disorders of carnitine, mitochondrial fatty acid and ketone body metabolism | 47 | 45/45 | 100% |
| Disorders of energy substrate metabolism | 43 | 40/43 | 93% |
| Endocrine metabolic disorders | 88 | 37/87 | 43% |
| Disorders of tetrapyrrole metabolism | 33 | 30/33 | 91% |
| Miscellaneous disorders of intermediary metabolism | 25 | 23/25 | 92% |
| Disorders of peptide and polyamine metabolism | 24 | 18/22 | 82% |
| Disorders of trace elements and metals | 49 | 16/48 | 33% |
| Other disorders of mitochondrial function | 59 | 14/59 | 24% |
| Neurotransmitter disorders | 74 | 13/74 | 18% |
| mtDNA-related disorders | 53 | 11/53 | 21% |
| Disorders of lipoprotein metabolism | 46 | 11/46 | 24% |
| Disorders of mitochondrial DNA maintenance and replication | 20 | 8/20 | 40% |
| Disorders of organelle biogenesis, dynamics and interactions | 141 | 4/141 | 3% |
| Disorders of mitochondrial cofactor biosynthesis | 33 | 3/33 | 9% |
| Disorders of mitochondrial gene expression | 69 | 2/69 | 3% |
| ICIMD category 25 (unnamed) | 28 | 1/27 | 4% |
| ICIMD category 26 (unnamed) | 210 | 0/210 | 0% |
Category = top-level icimdNosologyNumber mapped through reconws_icimd_nosology. Codes 25 & 26 are used by diseases but absent from that table (it stops at 24), so they show as "ICIMD category 25/26 (unnamed)" — a gap in the nosology table worth backfilling; 446 IMDs carry no ICIMD number at all.
IEMbase · ICIMD · WBM
Three disease sets across the whole catalogue, by identifier (not by diseaseSource): IEMbase = has an iemCode (2,343); ICIMD = has an icimdNosologyNumber (2,161); WBM = causal gene is in a WBM reaction (1,647). Every ICIMD disease also has an IEM code, so ICIMD nests entirely inside IEMbase.
Click a region to list the diseases in it. Across all 13,297 diseases; there is no ICIMD-only region (ICIMD ⊆ IEMbase).
The 614 "WBM only" diseases sit outside IEMbase but their causal gene is in a WBM reaction (mostly non-IEM OMIM / gene-association entries). There is no ICIMD-only or ICIMD-and-WBM-outside-IEMbase region — those are 0 by construction (ICIMD ⊆ IEMbase).
Modelled & treatable
WBM-covered IMDs that also have an orphan drug (from orphan drugs & the WBM) — both modelled and treatable, the cleanest demonstration cases. Drug→disease matching is lossy, so this is a lower bound.
| Disease | Gene | Orphan drug(s) |
|---|---|---|
| Alkaptonuria | HGD | Nitisinone |
| Fabry disease | GLA | Migalastat |
| Hereditary orotic aciduria | UMPS | Uridine triacetate |
| Homocystinuria, classical | CBS | Betaine |
| Maternal PKU syndrome | PAH | Sapropterin |
| Nephropathic cystinosis | CTNS | Mercaptamine |
| Phenylalanine hydroxylase deficiency | PAH | Sapropterin |
| Tyrosinemia type 1 | FAH | Nitisinone |
IMD universe = reconws_diseases where diseaseType = 'Inherited metabolic disease' (2607). Causal gene = gtr2, else the Entrez gene_id resolved to a symbol. WBM gene set = the 2019 distinct gene symbols in the reference WBM GPRs (wbm_reaction, models 3/4/187/188). WBM organs = the organs whose GPRs mention the gene (hover the count). Coverage is reported over the 2350 gene-bearing IMDs (1047/2350 = 45%), since the 257 with no recorded causal gene cannot be placed in a model; over all 2607 IMDs it is 1047/2607 = 40% (the figure on the /e/orphanDrugs tile).