North Carolina macular dystrophy

Summary

North Carolina macular dystrophy (MONDO:0007630) is a disease caused by PRDM13 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PRDM13 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	North Carolina macular dystrophy
Mondo ID	MONDO:0007630
MeSH	C537835
OMIM	136550
Orphanet	75327
DOID	DOID:0070439
ICD-11	1931008217
SNOMED CT	312925009
UMLS	C0730294
MedGen	147590
GARD	0009179
Is cancer (heuristic)	no

Also known as: CAPE dystrophy · CAPED · caped · central areolar pigment epithelial dystrophy · central retinal pigment epithelial dystrophy · foveal dystrophy progressive · foveal dystrophy, progressive · macular dystrophy 1, North Carolina type · macular dystrophy retinal 1 North Carolina type · macular dystrophy, retinal, 1, NORTH Carolina type · MCDR1 · NCMD · North Carolina macular dystrophy · North Carolina macular dystrophy, retinal 1 · progressive foveal dystrophy · retinal pigment epithelial dystrophy central

Data availability: 7 ClinVar variants · 3 GenCC gene-disease records · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › hereditary macular dystrophy › macular dystrophy, retinal › North Carolina macular dystrophy

Related subtypes (4): retinal macular dystrophy type 2, macular dystrophy, retinal, 3, macular dystrophy, retinal, 5, macular dystrophy, retinal, 4

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

7 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
446239	NC_000006.12:g.99593030G>T	LOC111365204	Pathogenic	criteria provided, single submitter
446240	NC_000006.12:g.99593111G>C	LOC111365204	Pathogenic	criteria provided, multiple submitters, no conflicts
625874	NC_000006.12:g.99598907A>C	LOC111365204	Pathogenic	no assertion criteria provided
812377	NC_000006.12:g.99593098A>C	LOC111365204	Pathogenic/Likely pathogenic	no assertion criteria provided
1213881	NM_021620.4(PRDM13):c.1714G>A (p.Gly572Ser)	PRDM13	Uncertain significance	criteria provided, single submitter
446241	NC_000006.12:g.99593164C>T	PRDM13	Uncertain significance	criteria provided, single submitter
963020	NM_021620.4(PRDM13):c.870C>T (p.Gly290=)	PRDM13	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 0 · 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
PRDM13	Definitive	Autosomal dominant	North Carolina macular dystrophy	9

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
PRDM13	HGNC:13998	ENSG00000112238	Q9H4Q3	PR domain zinc finger protein 13	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRDM13	PR domain zinc finger protein 13	May be involved in transcriptional regulation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRDM13	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf

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)	1
broad (>20)	0
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
hair follicle	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRDM13	7	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRDM13	1,187

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRDM13	Q9H4Q3	53.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
hypothalamus cell differentiation	1	3370.4×	7e-04	PRDM13
GABAergic neuron differentiation	1	3370.4×	7e-04	PRDM13
methylation	1	170.2×	0.010	PRDM13
regulation of gene expression	1	83.4×	0.015	PRDM13
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	PRDM13

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
PRDM13	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
PRDM13	1	Binding:1

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	0
E	Difficult family or no structure, no drug	1	PRDM13

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)
PRDM13	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.