Anterior segment dysgenesis 8

Summary

Anterior segment dysgenesis 8 (MONDO:0015017) is a disease caused by CPAMD8 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CPAMD8 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 24

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	anterior segment dysgenesis 8
Mondo ID	MONDO:0015017
OMIM	617319
Orphanet	519388
DOID	DOID:0080613
UMLS	C4310622
MedGen	934589
GARD	0017954
Is cancer (heuristic)	no

Also known as: anterior segment dysgenesis 8 · anterior segment dysgenesis caused by mutation in CPAMD8 · anterior segment dysgenesis type 8 · ASGD8 · CPAMD8 anterior segment dysgenesis · CPAMD8-related anterior segment dysgenesis

Data availability: 24 ClinVar variants · 3 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 8

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

24 retrieved; paginated sample, class counts are floors:

10 likely pathogenic, 7 uncertain significance, 3 pathogenic, 2 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1324164	NM_015692.5(CPAMD8):c.2070+1G>A	CPAMD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2574039	NM_015692.5(CPAMD8):c.1758+1_1758+4del	CPAMD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375309	NM_015692.5(CPAMD8):c.4210T>C (p.Ser1404Pro)	CPAMD8	Pathogenic	no assertion criteria provided
375310	NM_015692.5(CPAMD8):c.2211dup (p.Arg738fs)	CPAMD8	Pathogenic	criteria provided, multiple submitters, no conflicts
375311	NM_015692.5(CPAMD8):c.4408-1G>A	CPAMD8	Pathogenic	no assertion criteria provided
1333413	NM_015692.5(CPAMD8):c.2070+1G>C	CPAMD8	Likely pathogenic	criteria provided, single submitter
2442072	NM_015692.5(CPAMD8):c.-55G>A	CPAMD8	Likely pathogenic	criteria provided, single submitter
3235244	NM_015692.5(CPAMD8):c.4825C>T (p.Arg1609Ter)	CPAMD8	Likely pathogenic	criteria provided, single submitter
3235245	NM_015692.5(CPAMD8):c.534G>A (p.Trp178Ter)	CPAMD8	Likely pathogenic	criteria provided, single submitter
3250462	NM_015692.5(CPAMD8):c.2932C>T (p.Arg978Ter)	CPAMD8	Likely pathogenic	criteria provided, single submitter
3362554	NM_015692.5(CPAMD8):c.4396del (p.Gln1466fs)	CPAMD8	Likely pathogenic	criteria provided, single submitter
3382024	NM_015692.5(CPAMD8):c.3349C>T (p.Arg1117Ter)	CPAMD8	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4081285	NM_015692.5(CPAMD8):c.2070_2071insTTAA (p.Glu691fs)	CPAMD8	Likely pathogenic	criteria provided, single submitter
4292380	NM_015692.5(CPAMD8):c.3145-1G>T	CPAMD8	Likely pathogenic	criteria provided, single submitter
4849467	NM_015692.5(CPAMD8):c.2141del (p.Asp714fs)	CPAMD8	Likely pathogenic	criteria provided, single submitter
1027997	NM_015692.5(CPAMD8):c.173G>T (p.Arg58Met)	CPAMD8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2440522	NM_015692.5(CPAMD8):c.1994C>T (p.Thr665Met)	CPAMD8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2628068	NM_001123385.2(BCOR):c.716C>T (p.Thr239Ile)	BCOR	Uncertain significance	criteria provided, single submitter
1027996	NM_015692.5(CPAMD8):c.1916A>G (p.Gln639Arg)	CPAMD8	Uncertain significance	criteria provided, single submitter
2580881	NM_015692.5(CPAMD8):c.4028-1030T>C	CPAMD8	Uncertain significance	criteria provided, single submitter
2692330	NM_015692.5(CPAMD8):c.2066T>C (p.Phe689Ser)	CPAMD8	Uncertain significance	criteria provided, single submitter
3065142	NM_015692.5(CPAMD8):c.4710T>A (p.Asn1570Lys)	CPAMD8	Uncertain significance	criteria provided, single submitter
3065437	NM_015692.5(CPAMD8):c.1759-1G>A	CPAMD8	Uncertain significance	criteria provided, single submitter
3893072	NM_015692.5(CPAMD8):c.1395+5G>C	CPAMD8	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 5 · 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
CPAMD8	Strong	Autosomal recessive	anterior segment dysgenesis 8	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CPAMD8	Orphanet:519388	Autosomal recessive anterior segment dysgenesis
BCOR	Orphanet:2712	Oculofaciocardiodental syndrome
BCOR	Orphanet:457246	Clear cell sarcoma of kidney
BCOR	Orphanet:520	Acute promyelocytic leukemia
BCOR	Orphanet:568	Microphthalmia, Lenz type

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CPAMD8	HGNC:23228	ENSG00000160111	Q8IZJ3	C3 and PZP-like alpha-2-macroglobulin domain-containing protein 8	gencc,clinvar
BCOR	HGNC:20893	ENSG00000183337	Q6W2J9	BCL-6 corepressor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCOR	BCL-6 corepressor	Transcriptional corepressor.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Complement	1	134.0×	0.015
Scaffold/PPI	1	8.6×	0.112

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CPAMD8	Complement	yes		Macroglobln_a2, Kazal_dom, MG2
BCOR	Scaffold/PPI	no		Ankyrin_rpt, BCOR, PUFD

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
pancreatic ductal cell	1
right lung	1
buccal mucosa cell	1
cortical plate	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CPAMD8	227	broad	marker	apex of heart, pancreatic ductal cell, right lung
BCOR	265	ubiquitous	marker	buccal mucosa cell, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCOR	2,188
CPAMD8	692

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCOR	Q6W2J9	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CPAMD8	Q8IZJ3	72.99

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
specification of axis polarity	1	8426.0×	0.001	BCOR
negative regulation of tooth mineralization	1	4213.0×	0.001	BCOR
negative regulation of bone mineralization	1	468.1×	0.008	BCOR
blastocyst hatching	1	271.8×	0.008	BCOR
odontogenesis	1	263.3×	0.008	BCOR
eye development	1	175.5×	0.010	CPAMD8
roof of mouth development	1	123.9×	0.013	BCOR
heart development	1	39.4×	0.033	BCOR
chromatin remodeling	1	36.5×	0.033	BCOR
negative regulation of DNA-templated transcription	1	15.8×	0.069	BCOR
negative regulation of transcription by RNA polymerase II	1	8.9×	0.110	BCOR

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CPAMD8	0	0
BCOR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
BCOR	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	CPAMD8
E	Difficult family or no structure, no drug	1	BCOR

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CPAMD8	0	—
BCOR	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.