hereditary hypercarotenemia and vitamin A deficiency

Summary

hereditary hypercarotenemia and vitamin A deficiency (MONDO:0007272) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary hypercarotenemia and vitamin A deficiency
Mondo ID	MONDO:0007272
MeSH	C567296
OMIM	115300
Orphanet	199285
SNOMED CT	726079008
UMLS	C2676023
MedGen	393944
GARD	0017090
Is cancer (heuristic)	no

Also known as: HCVAD

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › disorder of metabolite absorption and transport › disorder of vitamin and non-protein cofactor absorption and transport › hereditary hypercarotenemia and vitamin A deficiency

Related subtypes (3): disorder of folate metabolism and transport, disorder of thiamine metabolism and transport, inborn disorder of cobalamin metabolism and transport

Subtypes (1): hypercarotenemia and vitamin A deficiency, autosomal recessive

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

4 retrieved; paginated sample, class counts are floors:

4 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3064733	NM_017429.3(BCO1):c.425A>G (p.Asn142Ser)	BCO1	Uncertain significance	criteria provided, single submitter
3778887	NM_017429.3(BCO1):c.1478A>T (p.Asp493Val)	BCO1	Uncertain significance	criteria provided, single submitter
3778888	NM_017429.3(BCO1):c.818G>T (p.Cys273Phe)	BCO1	Uncertain significance	criteria provided, single submitter
4772	NM_017429.3(BCO1):c.509C>T (p.Thr170Met)	BCO1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
BCO1	Supportive	Autosomal dominant	hereditary hypercarotenemia and vitamin A deficiency	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCO1	Orphanet:199285	Hereditary hypercarotenemia and vitamin A 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
BCO1	HGNC:13815	ENSG00000135697	Q9HAY6	Beta,beta-carotene 15,15’-dioxygenase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCO1	Beta,beta-carotene 15,15’-dioxygenase	Symmetrically cleaves beta-carotene into two molecules of retinal using a dioxygenase mechanism.

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)
BCO1	Enzyme (other)	yes	1.13.11.63	Carotenoid_Oase

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
jejunal mucosa	1
pigmented layer of retina	1
retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCO1	130	tissue_specific	marker	pigmented layer of retina, retina, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCO1	821

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BCO1	Q9HAY6	90.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Metabolism of fat-soluble vitamins	1	380.7×	0.008	BCO1
Visual phototransduction	1	259.6×	0.008	BCO1
Retinoid metabolism and transport	1	248.3×	0.008	BCO1
Metabolism of vitamins and cofactors	1	116.5×	0.013	BCO1
Sensory Perception	1	95.2×	0.013	BCO1
Metabolism	1	11.6×	0.086	BCO1

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
vitamin A biosynthetic process	1	16852.0×	2e-04	BCO1
beta-carotene metabolic process	1	16852.0×	2e-04	BCO1
carotene catabolic process	1	8426.0×	2e-04	BCO1
retinal metabolic process	1	936.2×	0.002	BCO1
retinoid metabolic process	1	495.6×	0.002	BCO1
retinol metabolic process	1	495.6×	0.002	BCO1

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
BCO1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BCO1	1.13.11.63	beta-carotene 15,15’-dioxygenase

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	1	BCO1
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)
BCO1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.