Pseudoxanthoma elasticum (inherited or acquired)

Summary

Pseudoxanthoma elasticum (inherited or acquired) (MONDO:0024308) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Cohort genes: 1
• ClinVar variants: 4
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pseudoxanthoma elasticum (inherited or acquired)
Mondo ID	MONDO:0024308
SNOMED CT	252246005
UMLS	C0033847
MedGen	18733
Is cancer (heuristic)	no

Also known as: PXE

Data availability: 4 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › pseudoxanthoma elasticum (inherited or acquired)

Related subtypes (35): Neu-Laxova syndrome, cutaneous mycosis, integumentary system benign neoplasm, integumentary system cancer, nipple neoplasm, nail disorder, disorder of pilosebaceous unit, Bartholin duct cyst, benign mammary dysplasia, skin disorder, breast fibrosis, breast mucosa-associated lymphoid tissue lymphoma, panniculitis, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, autosomal dominant deafness - onychodystrophy syndrome, keratoderma hereditarium mutilans, Rombo syndrome, Sjogren-Larsson syndrome, mucosulfatidosis, ichthyosis prematurity syndrome, ANE syndrome, frontonasal dysplasia with alopecia and genital anomaly, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, cutis laxa, X-linked ichthyosis syndrome, demodicidosis, Proteus-like syndrome, familial atypical multiple mole melanoma syndrome, familial tumoral calcinosis, subcutaneous tissue disorder, Bartholin gland neoplasm, skin appendage disorder, keratinization disease, paraneoplastic cutaneous syndrome

Subtypes (2): acquired pseudoxanthoma elasticum, inherited pseudoxanthoma elasticum

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:

2 pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3251661	NC_000016.9:g.(16244630_16248484)_(16259791_16263502)del	ABCC6	Pathogenic	criteria provided, single submitter
6560	NM_001171.6(ABCC6):c.2787+1G>T	ABCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
6559	NM_001171.6(ABCC6):c.3421C>T (p.Arg1141Ter)	ABCC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1017015	NM_001171.6(ABCC6):c.2530A>C (p.Lys844Gln)	ABCC6	Uncertain significance	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
ABCC6	Orphanet:51608	Generalized arterial calcification of infancy
ABCC6	Orphanet:758	Pseudoxanthoma elasticum

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
ABCC6	HGNC:57	ENSG00000091262	O95255	ATP-binding cassette sub-family C member 6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCC6	ATP-binding cassette sub-family C member 6	ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells.

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)
ABCC6	Transporter	yes	7.6.2.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP

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
duodenum	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCC6	136		marker	right lobe of liver, liver, duodenum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCC6	186

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCC6	O95255	4

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
Defective ABCC6 causes PXE	1	11420.0×	5e-04	ABCC6
ABC transporter disorders	1	439.2×	0.007	ABCC6
Disorders of transmembrane transporters	1	139.3×	0.012	ABCC6
ABC-family protein mediated transport	1	121.5×	0.012	ABCC6
Transport of small molecules	1	25.1×	0.048	ABCC6
Disease	1	13.1×	0.076	ABCC6

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
inorganic diphosphate transport	1	8426.0×	0.001	ABCC6
inhibition of non-skeletal tissue mineralization	1	4213.0×	0.001	ABCC6
leukotriene transport	1	2407.4×	0.001	ABCC6
response to sodium phosphate	1	1685.2×	0.001	ABCC6
intracellular phosphate ion homeostasis	1	1532.0×	0.001	ABCC6
ATP transport	1	1404.3×	0.001	ABCC6
response to magnesium ion	1	1404.3×	0.001	ABCC6
phosphate ion homeostasis	1	1053.2×	0.002	ABCC6
ATP metabolic process	1	468.1×	0.003	ABCC6
calcium ion homeostasis	1	443.5×	0.003	ABCC6
transmembrane transport	1	168.5×	0.008	ABCC6
gene expression	1	79.9×	0.014	ABCC6
visual perception	1	79.5×	0.014	ABCC6
response to xenobiotic stimulus	1	69.1×	0.014	ABCC6

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
ABCC6	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
ABCC6	10	Functional:9, Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABCC6	7.6.2.3	ABC-type glutathione-S-conjugate 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	ABCC6
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)
ABCC6	10	—

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
NCT00341419	Not specified	COMPLETED	Genetic Analysis of Patients With Pseudoxanthoma Elasticum