Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency

Summary

Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency (MONDO:0016203) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 15

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		24	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0001396	Cholestasis	Very frequent (80-99%)
HP:0001397	Hepatic steatosis	Very frequent (80-99%)
HP:0001403	Macrovesicular hepatic steatosis	Very frequent (80-99%)
HP:0002155	Hypertriglyceridemia	Very frequent (80-99%)
HP:0003124	Hypercholesterolemia	Very frequent (80-99%)
HP:0003141	Increased LDL cholesterol concentration	Very frequent (80-99%)
HP:0006573	Acute hepatic steatosis	Very frequent (80-99%)
HP:0011980	Cholesterol gallstones	Very frequent (80-99%)
HP:0012115	Hepatitis	Very frequent (80-99%)
HP:0001513	Obesity	Frequent (30-79%)
HP:0001677	Coronaryartery atherosclerosis	Frequent (30-79%)
HP:0004943	Accelerated atherosclerosis	Frequent (30-79%)
HP:0008372	Abnormality of vitamin A metabolism	Frequent (30-79%)
HP:0012397	Aortic atherosclerosis	Frequent (30-79%)
HP:0100514	Abnormality of vitamin E metabolism	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency
Mondo ID	MONDO:0016203
Orphanet	209902
UMLS	C4751204
MedGen	1653798
GARD	0020441
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

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 › familial hyperlipidemia › familial hypercholesterolemia › hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency

Related subtypes (4): hypercholesterolemia, familial, 1, hypercholesterolemia, autosomal dominant, type B, hypercholesterolemia, autosomal dominant, 3, homozygous familial hypercholesterolemia

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
CYP7A1	Supportive	Semidominant	hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYP7A1	Orphanet:209902	Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency

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
CYP7A1	HGNC:2651	ENSG00000167910	P22680	Cytochrome P450 7A1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYP7A1	Cytochrome P450 7A1	A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol and its oxygenated derivatives (oxysterols).

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CYP7A1	Enzyme (other)	yes	1.14.14.23	Cyt_P450, Cyt_P450_E_grp-IV, Cyt_P450_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
liver	1
primordial germ cell in gonad	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYP7A1	33	tissue_specific	marker	right lobe of liver, liver, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP7A1	2,612

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CYP7A1	P22680	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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 27-hydroxycholesterol	1	761.3×	0.003	CYP7A1
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol	1	456.8×	0.003	CYP7A1
Synthesis of bile acids and bile salts	1	407.9×	0.003	CYP7A1
Endogenous sterols	1	393.8×	0.003	CYP7A1
PPARA activates gene expression	1	94.4×	0.011	CYP7A1

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
regulation of bile acid biosynthetic process	1	2808.7×	0.002	CYP7A1
cholesterol catabolic process	1	1872.4×	0.002	CYP7A1
negative regulation of collagen biosynthetic process	1	1123.5×	0.002	CYP7A1
positive regulation of cholesterol biosynthetic process	1	1123.5×	0.002	CYP7A1
negative regulation of fatty acid biosynthetic process	1	887.0×	0.002	CYP7A1
sterol metabolic process	1	842.6×	0.002	CYP7A1
cellular response to cholesterol	1	842.6×	0.002	CYP7A1
bile acid biosynthetic process	1	624.1×	0.002	CYP7A1
cellular response to glucose stimulus	1	267.5×	0.005	CYP7A1
cholesterol homeostasis	1	156.0×	0.007	CYP7A1
response to ethanol	1	146.5×	0.007	CYP7A1

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
CYP7A1	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
CYP7A1	4	ADMET:3, Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CYP7A1	1.14.14.23	cholesterol 7alpha-monooxygenase

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	CYP7A1
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)
CYP7A1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.