Anterior segment dysgenesis 7

Summary

Anterior segment dysgenesis 7 (MONDO:0010015) is a disease caused by PXDN (GenCC Strong), with 3 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: PXDN (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 255

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	anterior segment dysgenesis 7
Mondo ID	MONDO:0010015
OMIM	269400
Orphanet	289499
DOID	DOID:0080612
UMLS	C3151617
MedGen	462967
GARD	0017327
Is cancer (heuristic)	no

Also known as: anterior segment dysgenesis 7 · anterior segment dysgenesis 7, with sclerocornea · anterior segment dysgenesis caused by mutation in PXDN · ASGD7 · CCMCO · COPOA · corneal opacification with other ocular anomalies · PXDN anterior segment dysgenesis · PXDN-related ocular dysgenesis · sclerocornea with other ocular anomalies

Data availability: 255 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › anterior segment dysgenesis › anterior segment dysgenesis 7

Related subtypes (7): anterior segment dysgenesis 1, iridogoniodysgenesis, Peters anomaly, congenital primary aphakia, anterior segment dysgenesis 6, anterior segment dysgenesis 8, isolated iridoschisis

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

255 retrieved; paginated sample, class counts are floors:

101 likely benign, 63 uncertain significance, 44 benign, 18 pathogenic, 18 benign/likely benign, 6 conflicting classifications of pathogenicity, 5 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1074765	NM_012293.3(PXDN):c.2350del (p.His784fs)	PXDN	Pathogenic	criteria provided, single submitter
1342666	NM_012293.3(PXDN):c.1109del (p.Pro370fs)	PXDN	Pathogenic	no assertion criteria provided
1399091	NM_012293.3(PXDN):c.2824C>T (p.Gln942Ter)	PXDN	Pathogenic	criteria provided, single submitter
140741	NM_012293.3(PXDN):c.2568del (p.Cys857fs)	PXDN	Pathogenic	no assertion criteria provided
140742	NM_012293.3(PXDN):c.2638C>T (p.Arg880Cys)	PXDN	Pathogenic	no assertion criteria provided
140743	NM_012293.3(PXDN):c.1021C>T (p.Arg341Ter)	PXDN	Pathogenic	no assertion criteria provided
140744	NM_012293.3(PXDN):c.2375_2397del (p.Leu792fs)	PXDN	Pathogenic	no assertion criteria provided
2015134	NM_012293.3(PXDN):c.1927C>T (p.Arg643Ter)	PXDN	Pathogenic	criteria provided, single submitter
2156476	NM_012293.3(PXDN):c.2353C>T (p.Arg785Ter)	PXDN	Pathogenic	criteria provided, single submitter
3064201	NM_012293.3(PXDN):c.3609-1G>C	PXDN	Pathogenic	criteria provided, single submitter
3610735	NM_012293.3(PXDN):c.2568dup (p.Cys857fs)	PXDN	Pathogenic	criteria provided, single submitter
694375	NM_012293.3(PXDN):c.2276C>T (p.Ser759Leu)	PXDN	Pathogenic	criteria provided, single submitter
694376	NM_012293.3(PXDN):c.4216_4225dup (p.Arg1409delinsProTer)	PXDN	Pathogenic	criteria provided, single submitter
694377	NM_012293.3(PXDN):c.2569del (p.Cys857fs)	PXDN	Pathogenic	criteria provided, multiple submitters, no conflicts
694378	NM_012293.3(PXDN):c.693_697dup (p.Val233fs)	PXDN	Pathogenic	criteria provided, single submitter
694379	NM_012293.3(PXDN):c.1A>G (p.Met1Val)	PXDN	Pathogenic	criteria provided, single submitter
932291	NM_012293.3(PXDN):c.4085_4086del (p.Gln1362fs)	PXDN	Pathogenic	criteria provided, multiple submitters, no conflicts
984974	NM_012293.3(PXDN):c.2098G>T (p.Gly700Ter)	PXDN	Pathogenic	criteria provided, single submitter
2432899	NM_012293.3(PXDN):c.3743+2T>G	PXDN	Likely pathogenic	criteria provided, single submitter
3064154	NM_012293.3(PXDN):c.1018+1G>A	PXDN	Likely pathogenic	criteria provided, single submitter
3255593	NM_012293.3(PXDN):c.3355_3356del (p.Arg1119fs)	PXDN	Likely pathogenic	criteria provided, single submitter
3362525	NM_012293.3(PXDN):c.3964del (p.Arg1322fs)	PXDN	Likely pathogenic	criteria provided, single submitter
4846916	NM_012293.3(PXDN):c.20del (p.Gly7fs)	PXDN	Likely pathogenic	criteria provided, single submitter
3428625	NM_012293.3(PXDN):c.1261G>A (p.Val421Ile)	PXDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
471914	NM_012293.3(PXDN):c.2827C>T (p.Arg943Trp)	PXDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
707047	NM_012293.3(PXDN):c.19G>T (p.Gly7Cys)	PXDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
707206	NM_012293.3(PXDN):c.1495C>G (p.Gln499Glu)	PXDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
771076	NM_012293.3(PXDN):c.481G>A (p.Glu161Lys)	PXDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
771087	NM_012293.3(PXDN):c.1112C>T (p.Pro371Leu)	PXDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1018179	NM_012293.3(PXDN):c.2369A>T (p.His790Leu)	PXDN	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 16 · 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
PXDN	Strong	Autosomal recessive	anterior segment dysgenesis 7	5
ATOH7	Supportive	Autosomal recessive	anterior segment dysgenesis 7	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PXDN	Orphanet:289499	Congenital cataract microcornea with corneal opacity
PXDN	Orphanet:699850	2p25.3 microduplication syndrome
ATOH7	Orphanet:289499	Congenital cataract microcornea with corneal opacity
ATOH7	Orphanet:91495	Persistent hyperplastic primary vitreous
RYR1	Orphanet:169186	Autosomal recessive centronuclear myopathy
RYR1	Orphanet:169189	Autosomal dominant centronuclear myopathy
RYR1	Orphanet:178145	Moderate multiminicore disease with hand involvement
RYR1	Orphanet:324581	Benign Samaritan congenital myopathy
RYR1	Orphanet:33108	Lethal multiple pterygium syndrome
RYR1	Orphanet:423	Malignant hyperthermia of anesthesia
RYR1	Orphanet:424107	Congenital myopathy with myasthenic-like onset
RYR1	Orphanet:466650	Exercise-induced malignant hyperthermia
RYR1	Orphanet:597	Central core disease
RYR1	Orphanet:700188	Calf-predominant weakness-gastrocnemius medialis atrophy-distal myopathy
RYR1	Orphanet:98905	Congenital multicore myopathy with external ophthalmoplegia
RYR1	Orphanet:99741	King-Denborough syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PXDN	HGNC:14966	ENSG00000130508	Q92626	Peroxidasin homolog	gencc,clinvar
ATOH7	HGNC:13907	ENSG00000179774	Q8N100	Transcription factor ATOH7	gencc
RYR1	HGNC:10483	ENSG00000196218	P21817	Ryanodine receptor 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PXDN	Peroxidasin homolog	Catalyzes the two-electron oxidation of bromide by hydrogen peroxide and generates hypobromite as a reactive intermediate which mediates the formation of sulfilimine cross-links between methionine and hydroxylysine residues within an uncro…
ATOH7	Transcription factor ATOH7	Transcription factor that binds to DNA at the consensus sequence 5’-CAG[GC]TG-3'.
RYR1	Ryanodine receptor 1	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.67

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
Ion channel	1	37.2×	0.080
Antibody/Immunoglobulin	1	9.7×	0.149
Transcription factor	1	2.8×	0.321

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PXDN	Antibody/Immunoglobulin	yes	1.11.1.7	Cys-rich_flank_reg_C, VWF_dom, Leu-rich_rpt
ATOH7	Transcription factor	no		bHLH_dom, ATOH7_bHLH, HLH_DNA-bd_sf
RYR1	Ion channel	yes		RIH_dom, B30.2/SPRY, Ryanodine_rcpt

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hair follicle	1
stromal cell of endometrium	1
tendon of biceps brachii	1
Brodmann (1909) area 9	1
male germ line stem cell (sensu Vertebrata) in testis	1
prefrontal cortex	1
gastrocnemius	1
gluteal muscle	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PXDN	265	ubiquitous	marker	stromal cell of endometrium, hair follicle, tendon of biceps brachii
ATOH7	104	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, prefrontal cortex, Brodmann (1909) area 9
RYR1	214	broad	marker	gluteal muscle, gastrocnemius, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PXDN	9,915
RYR1	2,177
ATOH7	1,076

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RYR1	P21817	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PXDN	Q92626	80.43
ATOH7	Q8N100	72.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	1	439.2×	0.014	PXDN
Crosslinking of collagen fibrils	1	285.5×	0.014	PXDN
Ion homeostasis	1	102.0×	0.026	RYR1
Stimuli-sensing channels	1	68.0×	0.028	RYR1
Cardiac conduction	1	54.4×	0.028	RYR1
Ion channel transport	1	48.0×	0.028	RYR1
Muscle contraction	1	38.6×	0.029	RYR1
Transport of small molecules	1	12.6×	0.078	RYR1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of retinal ganglion cell axon guidance	1	5617.3×	0.007	ATOH7
response to caffeine	1	802.5×	0.011	RYR1
basement membrane assembly	1	624.1×	0.011	PXDN
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	561.7×	0.011	RYR1
cellular response to caffeine	1	510.7×	0.011	RYR1
ossification involved in bone maturation	1	468.1×	0.011	RYR1
optic nerve development	1	401.2×	0.011	ATOH7
protein homotrimerization	1	330.4×	0.011	PXDN
neural retina development	1	312.1×	0.011	ATOH7
striated muscle contraction	1	280.9×	0.011	RYR1
neuron fate commitment	1	267.5×	0.011	ATOH7
response to auditory stimulus	1	244.2×	0.011	ATOH7
entrainment of circadian clock by photoperiod	1	244.2×	0.011	ATOH7
sensory organ development	1	224.7×	0.011	ATOH7
hydrogen peroxide catabolic process	1	224.7×	0.011	PXDN
skeletal muscle fiber development	1	181.2×	0.013	RYR1
basement membrane organization	1	170.2×	0.013	PXDN
axon development	1	151.8×	0.013	ATOH7
skin development	1	147.8×	0.013	RYR1
regulation of cytosolic calcium ion concentration	1	127.7×	0.015	RYR1
eye development	1	117.0×	0.015	PXDN
release of sequestered calcium ion into cytosol	1	114.6×	0.015	RYR1
outflow tract morphogenesis	1	102.1×	0.016	RYR1
circadian rhythm	1	81.4×	0.019	ATOH7
protein homotetramerization	1	79.1×	0.019	RYR1
collagen fibril organization	1	74.9×	0.019	PXDN
muscle contraction	1	69.3×	0.020	RYR1
cellular response to calcium ion	1	66.9×	0.020	RYR1
calcium ion transport	1	60.4×	0.022	RYR1
response to oxidative stress	1	43.5×	0.029	PXDN

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PXDN	0	0
ATOH7	0	0
RYR1	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
RYR1	16	Binding:13, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PXDN	1.11.1.7	peroxidase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
RYR1	1

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	RYR1
D	Druggable family + AlphaFold only, no drug	1	PXDN
E	Difficult family or no structure, no drug	1	ATOH7

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)
PXDN	0	—
ATOH7	0	—
RYR1	16	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.