Congenital bile acid synthesis defect 1

Summary

Congenital bile acid synthesis defect 1 (MONDO:0011906) is a disease caused by HSD3B7 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: HSD3B7 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 25
• Phenotypes (HPO): 16
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000952	Jaundice	Very frequent (80-99%)
HP:0001080	Biliary tract abnormality	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0002024	Malabsorption	Very frequent (80-99%)
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Very frequent (80-99%)
HP:0006566	Neonatal cholestatic liver disease	Very frequent (80-99%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0001928	Abnormality of coagulation	Frequent (30-79%)
HP:0002239	Gastrointestinal hemorrhage	Frequent (30-79%)
HP:0000662	Nyctalopia	Occasional (5-29%)
HP:0000939	Osteoporosis	Occasional (5-29%)
HP:0000989	Pruritus	Occasional (5-29%)
HP:0001394	Cirrhosis	Occasional (5-29%)
HP:0001892	Abnormal bleeding	Occasional (5-29%)
HP:0009830	Peripheral neuropathy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital bile acid synthesis defect 1
Mondo ID	MONDO:0011906
MeSH	C535442
OMIM	607765
Orphanet	79301
DOID	DOID:0111071
UMLS	C1843116
MedGen	335883
GARD	0009813
Is cancer (heuristic)	no

Also known as: 3-alpha beta-hydroxy-delta-5-C27-steroid oxidoreductase, deficiency of · 3-beta-hydroxy-delta-5-C27-steroid oxidoreductase deficiency type 1 · BASD1 · bile acid synthesis defect, congenital, 1 · bile acid synthesis defect, congenital, type 1 · CBAS1 · congenital bile acid synthesis defect 1 · congenital bile acid synthesis defect caused by mutation in HSD3B7 · congenital bile acid synthesis defect type 1 · congenital bile acid synthesis defect, type 1 · HSD3B7 congenital bile acid synthesis defect

Data availability: 25 ClinVar variants · 5 GenCC gene-disease records.

Disease family

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 › congenital bile acid synthesis defect 1

Related subtypes (5): congenital bile acid synthesis defect 4, congenital bile acid synthesis defect 2, 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

25 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 6 pathogenic, 6 likely pathogenic, 4 conflicting classifications of pathogenicity, 2 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1030914	NM_025193.4(HSD3B7):c.499G>T (p.Glu167Ter)	HSD3B7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191290	NM_025193.4(HSD3B7):c.694+2del	HSD3B7	Pathogenic	criteria provided, single submitter
2881	NM_025193.4(HSD3B7):c.1039_1040del (p.Leu347fs)	HSD3B7	Pathogenic	criteria provided, single submitter
2882	NM_025193.4(HSD3B7):c.294dup (p.Lys99fs)	HSD3B7	Pathogenic	criteria provided, multiple submitters, no conflicts
2884	NM_025193.4(HSD3B7):c.439G>A (p.Glu147Lys)	HSD3B7	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
4291805	NM_025193.4(HSD3B7):c.16C>T (p.Gln6Ter)	HSD3B7	Pathogenic	criteria provided, single submitter
2585402	NM_025193.4(HSD3B7):c.205C>T (p.Gln69Ter)	HSD3B7	Likely pathogenic	criteria provided, single submitter
2628801	NM_025193.4(HSD3B7):c.1025del (p.Phe342fs)	HSD3B7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2671755	NM_025193.4(HSD3B7):c.431+2T>C	HSD3B7	Likely pathogenic	criteria provided, single submitter
2883	NM_025193.4(HSD3B7):c.322+1G>T	HSD3B7	Likely pathogenic	criteria provided, single submitter
3580268	NM_025193.4(HSD3B7):c.323-1G>A	HSD3B7	Likely pathogenic	criteria provided, single submitter
3580269	NM_025193.4(HSD3B7):c.551del (p.Leu184fs)	HSD3B7	Likely pathogenic	criteria provided, single submitter
1687377	NM_025193.4(HSD3B7):c.682C>T (p.Arg228Trp)	HSD3B7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290373	NM_025193.4(HSD3B7):c.586G>A (p.Gly196Ser)	HSD3B7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
593732	NM_025193.4(HSD3B7):c.714C>T (p.His238=)	HSD3B7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
598247	NM_025193.4(HSD3B7):c.558G>A (p.Thr186=)	HSD3B7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030915	NM_025193.4(HSD3B7):c.557C>T (p.Thr186Met)	HSD3B7	Uncertain significance	criteria provided, single submitter
1339161	NM_025193.4(HSD3B7):c.689A>G (p.Tyr230Cys)	HSD3B7	Uncertain significance	criteria provided, single submitter
1342314	NM_025193.4(HSD3B7):c.1031A>G (p.Tyr344Cys)	HSD3B7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2432539	NM_025193.4(HSD3B7):c.143C>G (p.Pro48Arg)	HSD3B7	Uncertain significance	criteria provided, single submitter
2582472	NM_025193.4(HSD3B7):c.968C>T (p.Thr323Met)	HSD3B7	Uncertain significance	criteria provided, single submitter
2582473	NM_025193.4(HSD3B7):c.569G>A (p.Arg190His)	HSD3B7	Uncertain significance	criteria provided, single submitter
261870	NM_025193.4(HSD3B7):c.1068T>C (p.Arg356=)	HSD3B7	Benign	criteria provided, multiple submitters, no conflicts
261873	NM_025193.4(HSD3B7):c.748A>G (p.Thr250Ala)	HSD3B7	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
HSD3B7	Definitive	Autosomal recessive	congenital bile acid synthesis defect 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HSD3B7	Orphanet:79301	Congenital bile acid synthesis defect type 1

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
HSD3B7	HGNC:18324	ENSG00000099377	Q9H2F3	3 beta-hydroxysteroid dehydrogenase type 7	gencc,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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

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

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
left adrenal gland	1
liver	1
right lobe of liver	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HSD3B7	3,327

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

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 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
Synthesis of bile acids and bile salts via 24-hydroxycholesterol	1	878.5×	0.004	HSD3B7
Synthesis of bile acids and bile salts via 27-hydroxycholesterol	1	761.3×	0.004	HSD3B7
Bile acid and bile salt metabolism	1	496.5×	0.004	HSD3B7
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol	1	456.8×	0.004	HSD3B7
Synthesis of bile acids and bile salts	1	407.9×	0.004	HSD3B7
Metabolism of steroids	1	137.6×	0.010	HSD3B7
Metabolism of lipids	1	31.6×	0.036	HSD3B7
Metabolism	1	11.6×	0.086	HSD3B7

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
B cell chemotaxis	1	2808.7×	0.001	HSD3B7
bile acid biosynthetic process	1	624.1×	0.002	HSD3B7
steroid biosynthetic process	1	601.9×	0.002	HSD3B7

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
HSD3B7	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	HSD3B7

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)
HSD3B7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns