Hypercholanemia, familial
disease diseaseOn this page
Also known as familial hypercholanemia
Summary
Hypercholanemia, familial (MONDO:0100327) is a disease with 1 cohort gene.
At a glance
- Cohort genes: 1
- ClinVar variants: 5
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | hypercholanemia, familial |
| Mondo ID | MONDO:0100327 |
| OMIM | 607748 |
| UMLS | C1843139 |
| MedGen | 334689 |
| GARD | 0026146 |
| Is cancer (heuristic) | no |
Also known as: familial hypercholanemia · hypercholanemia, familial
Data availability: 5 ClinVar variants.
Disease family
An umbrella term covering 2 Mondo subtypes.
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of bile acid synthesis › hypercholanemia, familial
Related subtypes (4): cerebrotendinous xanthomatosis, hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency, bile acid CoA ligase deficiency and defective amidation, idiopathic malabsorption due to bile acid synthesis defects
Subtypes (2): hypercholanemia, familial, 2, hypercholanemia, familial 1
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
5 retrieved; paginated sample, class counts are floors:
4 pathogenic, 1 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2577971 | NM_016145.4(WDR83OS):c.255-4_260del | WDR83 | Pathogenic | criteria provided, single submitter |
| 3336829 | NM_016145.4(WDR83OS):c.50+1G>T | WDR83 | Pathogenic | criteria provided, single submitter |
| 3336830 | NM_016145.4(WDR83OS):c.156+2T>A | WDR83 | Pathogenic | criteria provided, single submitter |
| 3337986 | NM_016145.4(WDR83OS):c.235C>T (p.Gln79Ter) | WDR83 | Pathogenic | criteria provided, single submitter |
| 1329852 | NM_016145.4(WDR83OS):c.156+1G>T | WDR83 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| WDR83 | HGNC:32672 | ENSG00000123154 | Q9BRX9 | WD repeat domain-containing protein 83 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| WDR83 | WD repeat domain-containing protein 83 | Molecular scaffold protein for various multimeric protein complexes. |
Protein-family classification
Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0
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 | 1 | 17.3× | 0.058 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| WDR83 | Scaffold/PPI | no | WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene 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) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| cerebellar cortex | 1 |
| cerebellar hemisphere | 1 |
| right hemisphere of cerebellum | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| WDR83 | 182 | ubiquitous | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| WDR83 | 1,882 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| WDR83 | Q9BRX9 | 93.44 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| MAP2K and MAPK activation | 1 | 285.5× | 0.004 | WDR83 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| inflammatory response to wounding | 1 | 2106.5× | 0.003 | WDR83 |
| placenta blood vessel development | 1 | 1404.3× | 0.003 | WDR83 |
| RNA splicing, via transesterification reactions | 1 | 624.1× | 0.004 | WDR83 |
| regulation of canonical NF-kappaB signal transduction | 1 | 481.5× | 0.004 | WDR83 |
| neural tube closure | 1 | 187.2× | 0.009 | WDR83 |
| response to lipopolysaccharide | 1 | 124.8× | 0.011 | WDR83 |
| response to hypoxia | 1 | 95.8× | 0.011 | WDR83 |
| mRNA splicing, via spliceosome | 1 | 91.6× | 0.011 | WDR83 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| WDR83 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; 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 | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | WDR83 |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| WDR83 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.