Autosomal recessive inherited pseudoxanthoma elasticum

Summary

Autosomal recessive inherited pseudoxanthoma elasticum (MONDO:0009925) is a disease caused by ABCC6 (GenCC Definitive), with 6 cohort genes and 27 clinical trials. Top therapeutic interventions include aflibercept, etidronic acid, and magnesium oxide.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: ABCC6 (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 765
• Phenotypes (HPO): 41
• Clinical trials: 27

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	2.5	Europe	Validated

Signs & symptoms

Clinical features (HPO)

41 HPO clinical features (Orphanet curated; top 41 by frequency):

HPO ID	Term	Frequency
HP:0000474	Thickened nuchal skin fold	Very frequent (80-99%)
HP:0000488	Retinopathy	Very frequent (80-99%)
HP:0000573	Retinal hemorrhage	Very frequent (80-99%)
HP:0000951	Abnormality of the skin	Very frequent (80-99%)
HP:0001102	Angioid streaks of the fundus	Very frequent (80-99%)
HP:0007392	Excessive wrinkled skin	Very frequent (80-99%)
HP:0030680	Abnormal cardiovascular system morphology	Very frequent (80-99%)
HP:0100545	Arterial stenosis	Very frequent (80-99%)
HP:0100659	Abnormality of the cerebral vasculature	Very frequent (80-99%)
HP:0100679	Lack of skin elasticity	Very frequent (80-99%)
HP:0000978	Bruising susceptibility	Frequent (30-79%)
HP:0001065	Striae distensae	Frequent (30-79%)
HP:0001582	Redundant skin	Frequent (30-79%)
HP:0004417	Intermittent claudication	Frequent (30-79%)
HP:0025473	Hyperpigmented papule	Frequent (30-79%)
HP:0033027	Retinal peau d’orange	Frequent (30-79%)
HP:0000121	Nephrocalcinosis	Occasional (5-29%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000592	Blue sclerae	Occasional (5-29%)
HP:0000765	Abnormal thorax morphology	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0000974	Hyperextensible skin	Occasional (5-29%)
HP:0001012	Multiple lipomas	Occasional (5-29%)
HP:0001297	Stroke	Occasional (5-29%)
HP:0001482	Subcutaneous nodule	Occasional (5-29%)
HP:0001634	Mitral valve prolapse	Occasional (5-29%)
HP:0001645	Sudden cardiac death	Occasional (5-29%)
HP:0001650	Aortic valve stenosis	Occasional (5-29%)
HP:0001681	Angina pectoris	Occasional (5-29%)
HP:0001723	Restrictive cardiomyopathy	Occasional (5-29%)
HP:0001872	Abnormality of thrombocytes	Occasional (5-29%)
HP:0002172	Postural instability	Occasional (5-29%)
HP:0002239	Gastrointestinal hemorrhage	Occasional (5-29%)
HP:0002326	Transient ischemic attack	Occasional (5-29%)
HP:0002514	Cerebral calcification	Occasional (5-29%)
HP:0004306	Abnormality of the endocardium	Occasional (5-29%)
HP:0011506	Choroidal neovascularization	Occasional (5-29%)
HP:0012508	Metamorphopsia	Occasional (5-29%)
HP:0100585	Telangiectasia of the skin	Occasional (5-29%)
HP:0100817	Renovascular hypertension	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive inherited pseudoxanthoma elasticum
Mondo ID	MONDO:0009925
MeSH	D011561
OMIM	264800
Orphanet	758
DOID	DOID:2738
ICD-11	1516160852
NCIT	C85036
SNOMED CT	402782006, 72744008
GARD	0024699
MedDRA	10037150
NORD	1629
Is cancer (heuristic)	no

Also known as: AR inherited pseudoxanthoma elasticum · Gronblad Strandberg syndrome · Gronblad-Strandberg syndrome · Gronblad-Strandberg-Touraine syndrome · Pseudoxanthoma Elasticum · pseudoxanthoma elasticum · PXE

Data availability: 765 ClinVar variants · 6 GenCC gene-disease records · 28 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive inherited pseudoxanthoma elasticum

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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

600 retrieved; paginated sample, class counts are floors:

293 uncertain significance, 60 likely pathogenic, 58 conflicting classifications of pathogenicity, 55 pathogenic, 43 benign, 39 likely benign, 33 pathogenic/likely pathogenic, 19 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
194471	NM_000392.5(ABCC2):c.1967+1G>A	ABCC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067354	NM_001171.6(ABCC6):c.1255C>T (p.Arg419Trp)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179156	GRCh37/hg19 16p13.11(chr16:16248464-16259810)	ABCC6	Pathogenic	no assertion criteria provided
1456552	NM_001171.6(ABCC6):c.3887G>A (p.Gly1296Asp)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457838	NM_001171.6(ABCC6):c.3987dup (p.Ile1330fs)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802149	NM_001171.6(ABCC6):c.2738_2739del (p.Pro913fs)	ABCC6	Pathogenic	criteria provided, single submitter
208558	NM_001171.6(ABCC6):c.3306+1del	ABCC6	Pathogenic	criteria provided, single submitter
2420625	NM_001171.6(ABCC6):c.3510G>A (p.Trp1170Ter)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2572576	NM_001171.6(ABCC6):c.2035G>T (p.Glu679Ter)	ABCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
2580302	GRCh37/hg19 16p13.11(chr16:15475455-16308356)x1	ABCC6	Pathogenic	criteria provided, single submitter
265018	NM_001171.6(ABCC6):c.1553G>A (p.Arg518Gln)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265021	NM_001171.6(ABCC6):c.4016G>A (p.Arg1339His)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30337	NM_001171.6(ABCC6):c.2294G>A (p.Arg765Gln)	ABCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
30338	NM_001171.6(ABCC6):c.4216C>A (p.Gln1406Lys)	ABCC6	Pathogenic	no assertion criteria provided
30339	NM_001171.6(ABCC6):c.1552C>T (p.Arg518Ter)	ABCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
3376887	NM_001171.6(ABCC6):c.2279G>C (p.Arg760Pro)	ABCC6	Pathogenic	criteria provided, single submitter
3578536	NM_001171.6(ABCC6):c.4404-1G>A	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3578626	NM_001171.6(ABCC6):c.341_345+8delinsG	ABCC6	Pathogenic	criteria provided, single submitter
372294	NM_001171.6(ABCC6):c.1132C>T (p.Gln378Ter)	ABCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
372295	NM_001171.6(ABCC6):c.3491G>A (p.Arg1164Gln)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3780487	NM_001171.6(ABCC6):c.1741C>T (p.Gln581Ter)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
379930	NM_001171.6(ABCC6):c.2018T>C (p.Leu673Pro)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
381638	NM_001171.6(ABCC6):c.2420G>A (p.Arg807Gln)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
418938	NM_001171.6(ABCC6):c.196dup (p.Ser66fs)	ABCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
430158	NM_001171.6(ABCC6):c.1256G>A (p.Arg419Gln)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
433200	NM_001171.6(ABCC6):c.105del (p.Val37fs)	ABCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
433209	NM_001171.6(ABCC6):c.654G>T (p.Trp218Cys)	ABCC6	Pathogenic	no assertion criteria provided
433211	NM_001171.6(ABCC6):c.3722G>A (p.Trp1241Ter)	ABCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
433215	NM_001171.6(ABCC6):c.960del (p.Ser321fs)	ABCC6	Pathogenic	criteria provided, single submitter
433218	NM_001171.6(ABCC6):c.1087C>T (p.Gln363Ter)	ABCC6	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · Orphanet: 11 · 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
ABCC6	Definitive	Semidominant	inherited pseudoxanthoma elasticum	9
ENPP1	Supportive	Autosomal recessive	autosomal recessive inherited pseudoxanthoma elasticum	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCC6	Orphanet:51608	Generalized arterial calcification of infancy
ABCC6	Orphanet:758	Pseudoxanthoma elasticum
ENPP1	Orphanet:289176	Autosomal recessive hypophosphatemic rickets
ENPP1	Orphanet:324561	Hypopigmentation-punctate palmoplantar keratoderma syndrome
ENPP1	Orphanet:51608	Generalized arterial calcification of infancy
ENPP1	Orphanet:758	Pseudoxanthoma elasticum
XYLT1	Orphanet:1425	Desbuquois syndrome
XYLT1	Orphanet:370930	XYLT1-CDG
XYLT2	Orphanet:85194	Spondylo-ocular syndrome
ABCC1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
ABCC2	Orphanet:234	Dubin-Johnson syndrome

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABCC6	HGNC:57	ENSG00000091262	O95255	ATP-binding cassette sub-family C member 6	gencc,clinvar
ENPP1	HGNC:3356	ENSG00000197594	P22413	Ectonucleotide pyrophosphatase/phosphodiesterase family member 1	gencc
XYLT1	HGNC:15516	ENSG00000103489	Q86Y38	Xylosyltransferase 1	clinvar
XYLT2	HGNC:15517	ENSG00000015532	Q9H1B5	Xylosyltransferase 2	clinvar
ABCC1	HGNC:51	ENSG00000103222	P33527	Multidrug resistance-associated protein 1	clinvar
ABCC2	HGNC:53	ENSG00000023839	Q92887	ATP-binding cassette sub-family C member 2	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.
ENPP1	Ectonucleotide pyrophosphatase/phosphodiesterase family member 1	Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels.
XYLT1	Xylosyltransferase 1	Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN.
XYLT2	Xylosyltransferase 2	Catalyzes the first step in the biosynthesis of chondroitin sulfate, heparan sulfate and dermatan sulfate proteoglycans, such as DCN.
ABCC1	Multidrug resistance-associated protein 1	Mediates export of organic anions and drugs from the cytoplasm.
ABCC2	ATP-binding cassette sub-family C member 2	ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes.

Protein-family classification

Druggable: 6 · 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	3	38.9×	1e-04
Phosphatase	1	14.0×	0.083
Enzyme (other)	2	4.0×	0.083

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
ENPP1	Phosphatase	yes	3.6.1.9	Somatomedin_B_dom, Endo_G_ENPP1-like_dom, Phosphodiest/P_Trfase
XYLT1	Enzyme (other)	yes	2.4.2.26	Glyco_trans_14, XylT_C, XYLT
XYLT2	Enzyme (other)	yes	2.4.2.26	Glyco_trans_14, XylT_C, XYLT
ABCC1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP
ABCC2	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP

Expression context

Cohort genes with no expression data: 0.

6 cohort genes 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	2
right lobe of liver	2
cartilage tissue	2
tibia	2
duodenum	1
decidua	1
hair follicle	1
body of stomach	1
fundus of stomach	1
stomach	1
lower esophagus	1
lower esophagus mucosa	1
lower esophagus muscularis layer	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCC6	136		marker	right lobe of liver, liver, duodenum
ENPP1	227	ubiquitous	marker	tibia, decidua, cartilage tissue
XYLT1	272	broad	marker	tibia, cartilage tissue, hair follicle
XYLT2	237	ubiquitous	marker	body of stomach, stomach, fundus of stomach
ABCC1	134	ubiquitous	marker	lower esophagus mucosa, lower esophagus, lower esophagus muscularis layer
ABCC2	171	broad	marker	right lobe of liver, liver, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCC1	3,018
ABCC2	2,725
ENPP1	1,911
XYLT2	850
XYLT1	704
ABCC6	186

Intra-cohort edges

A	B	Sources
XYLT1	XYLT2	biogrid_interaction

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCC2	Q92887	16
XYLT1	Q86Y38	9
ENPP1	P22413	7
ABCC1	P33527	5
ABCC6	O95255	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
XYLT2	Q9H1B5	84.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 6 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Metabolism of porphyrins	2	475.8×	2e-04	ABCC1, ABCC2
ABC-family protein mediated transport	3	60.7×	2e-04	ABCC6, ABCC1, ABCC2
Heme degradation	2	271.9×	2e-04	ABCC1, ABCC2
ABC transporter disorders	2	146.4×	5e-04	ABCC6, ABCC2
Paracetamol ADME	2	141.0×	5e-04	ABCC1, ABCC2
Glycosaminoglycan-protein linkage region biosynthesis	2	131.3×	5e-04	XYLT1, XYLT2
Drug ADME	2	76.1×	0.001	ABCC1, ABCC2
Defective ABCC2 causes DJS	1	1903.3×	0.002	ABCC2
Defective ABCC6 causes PXE	1	1903.3×	0.002	ABCC6
Disorders of transmembrane transporters	2	46.4×	0.003	ABCC6, ABCC2
Transport of small molecules	3	12.6×	0.004	ABCC6, ABCC1, ABCC2
Vitamin B2 (riboflavin) metabolism	1	271.9×	0.010	ENPP1
Atorvastatin ADME	1	237.9×	0.010	ABCC2
Transport of RCbl within the body	1	237.9×	0.010	ABCC1
NFE2L2 regulating MDR associated enzymes	1	237.9×	0.010	ABCC1
Vitamin B5 (pantothenate) metabolism	1	126.9×	0.017	ENPP1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1	105.7×	0.019	ABCC1
Synthesis of Leukotrienes (LT) and Eoxins (EX)	1	95.2×	0.019	ABCC1
Arachidonate metabolism	1	95.2×	0.019	ABCC1
Nuclear events mediated by NFE2L2	1	56.0×	0.030	ABCC1
Aspirin ADME	1	52.9×	0.030	ABCC2
Sphingolipid de novo biosynthesis	1	47.6×	0.032	ABCC1
Cytoprotection by HMOX1	1	30.7×	0.046	ABCC1
Metabolism of water-soluble vitamins and cofactors	1	30.2×	0.046	ABCC1
Sphingolipid metabolism	1	28.0×	0.048	ABCC1
Cellular response to chemical stress	1	23.8×	0.054	ABCC1
Fatty acid metabolism	1	21.9×	0.056	ABCC1
KEAP1-NFE2L2 pathway	1	20.0×	0.059	ABCC1
Metabolism of vitamins and cofactors	1	19.4×	0.059	ABCC1
Disease	2	4.4×	0.081	ABCC6, ABCC2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
leukotriene transport	3	1203.7×	1e-07	ABCC6, ABCC1, ABCC2
inorganic diphosphate transport	2	2808.7×	6e-06	ABCC6, ENPP1
gene expression	4	53.2×	1e-05	ABCC6, ENPP1, ABCC1, ABCC2
glycosaminoglycan-protein linkage region biosynthetic process	2	1404.3×	2e-05	XYLT1, XYLT2
xenobiotic transport across blood-brain barrier	2	936.2×	4e-05	ABCC1, ABCC2
transmembrane transport	3	84.3×	7e-05	ABCC6, ABCC1, ABCC2
intracellular phosphate ion homeostasis	2	510.7×	8e-05	ABCC6, ENPP1
heme catabolic process	2	510.7×	8e-05	ABCC1, ABCC2
transepithelial transport	2	401.2×	1e-04	ABCC1, ABCC2
phosphate ion homeostasis	2	351.1×	1e-04	ABCC6, ENPP1
glycosaminoglycan biosynthetic process	2	280.9×	2e-04	XYLT1, XYLT2
chondroitin sulfate proteoglycan biosynthetic process	2	208.1×	3e-04	XYLT1, XYLT2
heparan sulfate proteoglycan biosynthetic process	2	187.2×	4e-04	XYLT1, XYLT2
ATP metabolic process	2	156.0×	5e-04	ABCC6, ENPP1
glutathione metabolic process	2	117.0×	9e-04	ABCC1, ABCC2
glucuronoside transport	1	2808.7×	0.002	ABCC2
antigen processing and presentation of lipid antigen via MHC class Ib	1	2808.7×	0.002	ABCC1
cyclic nucleotide transport	1	2808.7×	0.002	ABCC1
sphingolipid translocation	1	2808.7×	0.002	ABCC1
intracellular nitrogen homeostasis	1	2808.7×	0.002	ABCC1
obsolete negative regulation of hh target transcription factor activity	1	2808.7×	0.002	ENPP1
transport across blood-brain barrier	2	59.8×	0.002	ABCC1, ABCC2
mercury ion transport	1	1404.3×	0.003	ABCC2
bilirubin transport	1	1404.3×	0.003	ABCC2
pigment accumulation	1	1404.3×	0.003	ABCC1
response to wortmannin	1	1404.3×	0.003	ABCC2
xenobiotic metabolic process	2	49.7×	0.003	ABCC1, ABCC2
granuloma formation	1	936.2×	0.004	ABCC1
glutathione transport	1	936.2×	0.004	ABCC2
xenobiotic export from cell	1	936.2×	0.004	ABCC2

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Etidronic Acid	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aflibercept, Magnesium Oxide.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 3

Druggability breadth: 4 of 6 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ABCC1	RIMONABANT
ABCC2	SIMVASTATIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCC2	35	4
ABCC1	23	4
ENPP1	1	3
ABCC6	0	0
XYLT1	0	0
XYLT2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1, ABCC2
CYCLOSPORINE	4	ABCC1, ABCC2
DAUNORUBICIN	4	ABCC1, ABCC2
ETRAVIRINE	4	ABCC1, ABCC2
BENZBROMARONE	4	ABCC1, ABCC2
ESTRONE SULFURIC ACID	4	ABCC1
DOXORUBICIN	4	ABCC1
MITOXANTRONE	4	ABCC1
INDOMETHACIN	4	ABCC1
IVERMECTIN	4	ABCC1, ABCC2
VERAPAMIL	4	ABCC1
VINCRISTINE	4	ABCC1
SIMVASTATIN	4	ABCC2
VALRUBICIN	4	ABCC2
LEUPROLIDE ACETATE	4	ABCC2
TEMSIROLIMUS	4	ABCC2
REPAGLINIDE	4	ABCC2
CLOFAZIMINE	4	ABCC2
CEFIXIME	4	ABCC2
RIFAXIMIN	4	ABCC2
RIFAPENTINE	4	ABCC2
EVEROLIMUS	4	ABCC2
TACROLIMUS ANHYDROUS	4	ABCC2
RIFAMPIN	4	ABCC2
DAPTOMYCIN	4	ABCC2
RIFABUTIN	4	ABCC2
ETHACRYNIC ACID	4	ABCC2
ERLOTINIB	4	ABCC2
EPALRESTAT	4	ABCC2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ABCC1	459	Binding:270, Functional:166, ADMET:23
ENPP1	167	Binding:154, ADMET:13
ABCC2	159	Functional:84, ADMET:40, Binding:35
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
ENPP1	3.6.1.9	nucleotide diphosphatase
XYLT1	2.4.2.26	protein xylosyltransferase
XYLT2	2.4.2.26	protein xylosyltransferase
ABCC1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter
ABCC2	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ENPP1	167
ABCC1	459
ABCC2	159

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1, ABCC2
CYCLOSPORINE	4	ABCC1, ABCC2
DAUNORUBICIN	4	ABCC1, ABCC2
ETRAVIRINE	4	ABCC1, ABCC2
BENZBROMARONE	4	ABCC1, ABCC2
ESTRONE SULFURIC ACID	4	ABCC1
DOXORUBICIN	4	ABCC1
MITOXANTRONE	4	ABCC1
INDOMETHACIN	4	ABCC1
IVERMECTIN	4	ABCC1, ABCC2
VERAPAMIL	4	ABCC1
VINCRISTINE	4	ABCC1
SIMVASTATIN	4	ABCC2
VALRUBICIN	4	ABCC2
LEUPROLIDE ACETATE	4	ABCC2
TEMSIROLIMUS	4	ABCC2
REPAGLINIDE	4	ABCC2
CLOFAZIMINE	4	ABCC2
CEFIXIME	4	ABCC2
RIFAXIMIN	4	ABCC2
RIFAPENTINE	4	ABCC2
EVEROLIMUS	4	ABCC2
TACROLIMUS ANHYDROUS	4	ABCC2
RIFAMPIN	4	ABCC2
DAPTOMYCIN	4	ABCC2
RIFABUTIN	4	ABCC2
ETHACRYNIC ACID	4	ABCC2
ERLOTINIB	4	ABCC2
EPALRESTAT	4	ABCC2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	ABCC1, ABCC2
B	Phased (≥1) drug, not yet approved	1	ENPP1
C	Druggable family + PDB, no drug	2	ABCC6, XYLT1
D	Druggable family + AlphaFold only, no drug	1	XYLT2
E	Difficult family or no structure, no drug	0

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ABCC6	10	—
XYLT1	0	—
XYLT2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 27.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	18
PHASE2	5
PHASE1/PHASE2	2
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05832580	PHASE3	RECRUITING	The Prevention of Systemic Ectopic Mineralization in Pseudoxanthoma Elasticum
NCT06462547	PHASE2	RECRUITING	ADAPT Study: Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 Deficiency
NCT00470977	PHASE1/PHASE2	COMPLETED	Treatment of Exudative and Vasogenic Chorioretinal Diseases Including Variants of AMD and Other CNV Related Maculopathy
NCT01525875	PHASE2	COMPLETED	Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)
NCT02537054	PHASE2	COMPLETED	Intravitreal Aflibercept for Therapy of Patients With Pseudoxanthoma Elasticum (PXE)
NCT04441671	PHASE2	WITHDRAWN	Oral Pyrophosphate Absorption in PXE Disease
NCT05030831	PHASE1/PHASE2	COMPLETED	Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in Adults With ABCC6 Deficiency Causing PXE
NCT05569252	PHASE2	COMPLETED	A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum
NCT05734196	PHASE1	RECRUITING	The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 Deficiency
NCT04868578	Not specified	RECRUITING	PPI Supplementation to Fight ECtopIc Calcification in PXE
NCT05662085	Not specified	ACTIVE_NOT_RECRUITING	Progression Rate of Pseudoxanthoma Elasticum-associated Choroidal and Retinal Degeneration
NCT06636344	Not specified	RECRUITING	Impact of Optimized Recruitment and Follow-up of Patients With Pseudoxanthoma Elasticum (PXE)
NCT07006649	Not specified	RECRUITING	CHOPXE - Analysis of Choriocapillaris Flow Deficits in Patients With Pseudoxanthoma Elasticum
NCT07048106	Not specified	RECRUITING	Progression Assessment of PXE-associated Alterations
NCT07323082	Not specified	RECRUITING	Purinergic Compounds in Pseudoxanthoma Elasticum
NCT00341419	Not specified	COMPLETED	Genetic Analysis of Patients With Pseudoxanthoma Elasticum
NCT00555113	Not specified	COMPLETED	Evolution of Visual Impairment During Pseudoxanthoma Elasticum
NCT01446380	Not specified	UNKNOWN	Phenotypic Expressions in a French Pseudoxanthoma-Elasticum Cohort
NCT01446393	Not specified	COMPLETED	Functional and Structural Characterization of Arteriopathy in Pseudoxanthoma Elasticum (PXE)
NCT01731080	Not specified	UNKNOWN	Arterial Wall Calcium Load in Pseudoxanthoma Elasticum
NCT02108392	Not specified	UNKNOWN	Characterization of Pseudoxanthoma Elasticum
NCT03070860	Not specified	COMPLETED	What’s Happen Under the Calcification Process in Pseudoxanthoma Elasticum
NCT03364504	Not specified	UNKNOWN	Biological Collection of Kidney Cells
NCT03758534	Not specified	UNKNOWN	Natural History of GACI With or Without ARHR2 or PXE
NCT03813550	Not specified	UNKNOWN	Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)
NCT05025722	Not specified	COMPLETED	Pseudoxanthoma Elasticum (PXE) Natural History Biomarkers in PXE Individuals and Their Biological Non-PXE Siblings
NCT05246189	Not specified	COMPLETED	Employment of Patients With Pseudoxanthoma Elasticum

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AFLIBERCEPT	4	1
ETIDRONIC ACID	4	1
MAGNESIUM OXIDE	4	1
INZ-701	3	3
SODIUM ACID PYROPHOSPHATE	2	1