Congenital bile acid synthesis defect 5

Summary

Congenital bile acid synthesis defect 5 (MONDO:0014564) 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	congenital bile acid synthesis defect 5
Mondo ID	MONDO:0014564
OMIM	616278
DOID	DOID:0111066
UMLS	C4225390
MedGen	904751
GARD	0025002
Is cancer (heuristic)	no

Also known as: ABCD3 congenital bile acid synthesis defect · bile acid synthesis defect, congenital, 5 · bile acid synthesis defect, congenital, type 5 · CBAS5 · congenital bile acid synthesis defect caused by mutation in ABCD3 · congenital bile acid synthesis defect type 5

Data availability: 5 ClinVar variants · 3 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 5

Related subtypes (5): 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 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

5 retrieved; paginated sample, class counts are floors:

3 benign, 1 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
187846	NM_002858.4(ABCD3):c.1903-573_*1108del	ABCD3	Pathogenic	no assertion criteria provided
1188883	NM_002858.4(ABCD3):c.1846-31C>G	ABCD3	Benign	criteria provided, multiple submitters, no conflicts
258821	NM_002858.4(ABCD3):c.162G>A (p.Lys54=)	ABCD3	Benign	criteria provided, multiple submitters, no conflicts
2921016	NM_002858.4(ABCD3):c.684+228G>A	ABCD3	Likely benign	criteria provided, single submitter
718421	NM_002858.4(ABCD3):c.155G>T (p.Gly52Val)	ABCD3	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
ABCD3	Moderate	Autosomal recessive	congenital bile acid synthesis defect 5	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCD3	Orphanet:98897	Oculopharyngodistal myopathy

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
ABCD3	HGNC:67	ENSG00000117528	P28288	ATP-binding cassette sub-family D member 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCD3	ATP-binding cassette sub-family D member 3	Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that catalyzes the transport of long-chain fatty acids (LCFA)-CoA, dicarboxylic acids-CoA, long-branched-chain fatty acids-CoA and bile acids fr…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCD3	Transporter	yes	7.6.2.4	ABC_transporter-like_ATP-bd, AAA+_ATPase, FA_transporter

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
epithelium of nasopharynx	1
jejunal mucosa	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCD3	295	ubiquitous	marker	secondary oocyte, jejunal mucosa, epithelium of nasopharynx

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCD3	1,856

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCD3	P28288	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
ABC transporters in lipid homeostasis	1	601.0×	0.011	ABCD3
Class I peroxisomal membrane protein import	1	519.1×	0.011	ABCD3
Protein localization	1	190.3×	0.018	ABCD3
RHOC GTPase cycle	1	146.4×	0.018	ABCD3
ABC-family protein mediated transport	1	121.5×	0.018	ABCD3
RHOA GTPase cycle	1	74.6×	0.025	ABCD3
RHO GTPase cycle	1	60.1×	0.026	ABCD3
Signaling by Rho GTPases	1	34.2×	0.036	ABCD3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.036	ABCD3
Transport of small molecules	1	25.1×	0.044	ABCD3
Signal Transduction	1	10.2×	0.098	ABCD3

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
phytanic acid metabolic process	1	8426.0×	0.001	ABCD3
long-chain fatty acid import into peroxisome	1	3370.4×	0.001	ABCD3
very long-chain fatty acid catabolic process	1	2407.4×	0.001	ABCD3
peroxisome organization	1	802.5×	0.002	ABCD3
very long-chain fatty acid metabolic process	1	766.0×	0.002	ABCD3
bile acid and bile salt transport	1	648.1×	0.002	ABCD3
bile acid biosynthetic process	1	624.1×	0.002	ABCD3
fatty acid beta-oxidation	1	374.5×	0.003	ABCD3
fatty acid biosynthetic process	1	351.1×	0.003	ABCD3
response to xenobiotic stimulus	1	69.1×	0.014	ABCD3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCD3	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
ABCD3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABCD3	7.6.2.4	ABC-type fatty-acyl-CoA transporter

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	1	ABCD3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
ABCD3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.