Congenital bile acid synthesis defect
disease diseaseOn this page
Also known as BASDbile acid synthesis defect, congenitalcholestasis with delta(4)-3-oxosteroid-5-beta-reductase deficiency
Summary
Congenital bile acid synthesis defect (MONDO:0018841) is a disease (an umbrella term covering 6 Mondo subtypes) with 2 cohort genes.
At a glance
- Umbrella term: 6 Mondo subtypes
- Cohort genes: 2
- ClinVar variants: 2
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | congenital bile acid synthesis defect |
| Mondo ID | MONDO:0018841 |
| EFO | EFO:0009039 |
| OMIM | 607765 |
| Orphanet | 485631 |
| DOID | DOID:0050674 |
| UMLS | C5680095 |
| MedGen | 1826069 |
| GARD | 0021996 |
| Is cancer (heuristic) | no |
Also known as: BASD · bile acid synthesis defect, congenital · cholestasis with delta(4)-3-oxosteroid-5-beta-reductase deficiency
Data availability: 2 ClinVar variants.
Disease family
An umbrella term covering 6 Mondo subtypes.
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › steroid inherited metabolic disorder › congenital bile acid synthesis defect
Related subtypes (2): apparent mineralocorticoid excess, congenital adrenal hyperplasia
Subtypes (6): congenital bile acid synthesis defect 4, congenital bile acid synthesis defect 2, congenital bile acid synthesis defect 1, congenital bile acid synthesis defect 3, congenital bile acid synthesis defect 5, congenital bile acid synthesis defect 6
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
2 retrieved; paginated sample, class counts are floors:
1 pathogenic, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 5378 | NM_005989.4(AKR1D1):c.781C>T (p.Arg261Cys) | AKR1D1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2885 | NM_025193.4(HSD3B7):c.45_46del (p.Gly17fs) | HSD3B7 | Pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| HSD3B7 | Orphanet:79301 | Congenital bile acid synthesis defect type 1 |
| AKR1D1 | Orphanet:79303 | Congenital bile acid synthesis defect type 2 |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| HSD3B7 | HGNC:18324 | ENSG00000099377 | Q9H2F3 | 3 beta-hydroxysteroid dehydrogenase type 7 | clinvar |
| AKR1D1 | HGNC:388 | ENSG00000122787 | P51857 | Aldo-keto reductase family 1 member D1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| HSD3B7 | 3 beta-hydroxysteroid dehydrogenase type 7 | The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. |
| AKR1D1 | Aldo-keto reductase family 1 member D1 | Catalyzes the stereospecific NADPH-dependent reduction of the C4-C5 double bond of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure to yield an A/B cis-ring junction. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5
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 |
|---|---|---|---|
| Enzyme (other) | 1 | 6.0× | 0.320 |
| Other/Unknown | 1 | 0.9× | 0.805 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| HSD3B7 | Other/Unknown | no | 3Beta_OHSteriod_DH/Estase, NAD(P)-bd_dom_sf, NAD(P)_dehydrat-like | |
| AKR1D1 | Enzyme (other) | yes | 1.3.1.3 | Aldo/ket_reductase_CS, AKR, NADP_OxRdtase_dom |
Expression context
Cohort genes with no expression data: 0.
2 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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| liver | 2 |
| right lobe of liver | 2 |
| left adrenal gland | 1 |
| primordial germ cell in gonad | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| HSD3B7 | 177 | ubiquitous | marker | right lobe of liver, liver, left adrenal gland |
| AKR1D1 | 85 | tissue_specific | marker | liver, right lobe of liver, primordial germ cell in gonad |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| HSD3B7 | 3,327 |
| AKR1D1 | 1,544 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| AKR1D1 | HSD3B7 | string_interaction |
Structural data
PDB: 1 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| AKR1D1 | P51857 | 14 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| HSD3B7 | Q9H2F3 | 94.01 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Synthesis of bile acids and bile salts via 24-hydroxycholesterol | 2 | 878.5× | 6e-06 | HSD3B7, AKR1D1 |
| Synthesis of bile acids and bile salts via 27-hydroxycholesterol | 2 | 761.3× | 6e-06 | HSD3B7, AKR1D1 |
| Bile acid and bile salt metabolism | 2 | 496.5× | 9e-06 | HSD3B7, AKR1D1 |
| Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol | 2 | 456.8× | 9e-06 | HSD3B7, AKR1D1 |
| Synthesis of bile acids and bile salts | 2 | 407.9× | 9e-06 | HSD3B7, AKR1D1 |
| Metabolism of steroids | 2 | 137.6× | 7e-05 | HSD3B7, AKR1D1 |
| Metabolism of lipids | 2 | 31.6× | 0.001 | HSD3B7, AKR1D1 |
| Metabolism | 2 | 11.6× | 0.007 | HSD3B7, AKR1D1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| bile acid biosynthetic process | 2 | 624.1× | 2e-05 | HSD3B7, AKR1D1 |
| bile acid catabolic process | 1 | 4213.0× | 9e-04 | AKR1D1 |
| C21-steroid hormone metabolic process | 1 | 1685.2× | 0.001 | AKR1D1 |
| B cell chemotaxis | 1 | 1404.3× | 0.001 | HSD3B7 |
| cholesterol catabolic process | 1 | 936.2× | 0.002 | AKR1D1 |
| androgen metabolic process | 1 | 443.5× | 0.003 | AKR1D1 |
| digestion | 1 | 312.1× | 0.003 | AKR1D1 |
| steroid biosynthetic process | 1 | 300.9× | 0.003 | HSD3B7 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| HSD3B7 | 0 | 0 |
| AKR1D1 | 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 |
|---|---|---|
| AKR1D1 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| AKR1D1 | 1.3.1.3 | DELTA4-3-oxosteroid 5beta-reductase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 2; 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 | AKR1D1 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | HSD3B7 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| HSD3B7 | 0 | — |
| AKR1D1 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.