Patterned macular dystrophy 3

Summary

Patterned macular dystrophy 3 (MONDO:0014920) is a disease caused by MAPKAPK3 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MAPKAPK3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		14	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	patterned macular dystrophy 3
Mondo ID	MONDO:0014920
OMIM	617111
Orphanet	466718
DOID	DOID:0060865
UMLS	C4310713
MedGen	934680
GARD	0017826
Is cancer (heuristic)	no

Also known as: macular dystrophy, patterned, 3 · macular dystrophy, patterned, type 3 · MAPKAPK3 patterned macular dystrophy · Martinique crinkled retinal pigment epitheliopathy · MCRPE · MDPT3 · patterned macular dystrophy caused by mutation in MAPKAPK3 · patterned macular dystrophy type 3

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

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › patterned macular dystrophy › patterned macular dystrophy 3

Related subtypes (2): patterned macular dystrophy 1, patterned macular dystrophy 2

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

3 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
254177	NM_001243925.2(MAPKAPK3):c.518T>C (p.Leu173Pro)	MAPKAPK3	Pathogenic	no assertion criteria provided
1587693	NM_001243925.2(MAPKAPK3):c.82C>G (p.Pro28Ala)	MAPKAPK3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2627452	NM_001243925.2(MAPKAPK3):c.900C>G (p.Asn300Lys)	MAPKAPK3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
MAPKAPK3	Strong	Autosomal dominant	patterned macular dystrophy 3	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAPKAPK3	Orphanet:466718	Martinique crinkled retinal pigment epitheliopathy

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
MAPKAPK3	HGNC:6888	ENSG00000114738	Q16644	MAP kinase-activated protein kinase 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAPKAPK3	MAP kinase-activated protein kinase 3	Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAPKAPK3	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_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)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
cardiac ventricle	1
heart left ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAPKAPK3	278	ubiquitous	marker	apex of heart, heart left ventricle, cardiac ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAPKAPK3	1,130

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAPKAPK3	Q16644	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 36. 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
p38MAPK events	1	878.5×	0.010	MAPKAPK3
Signalling to RAS	1	671.8×	0.010	MAPKAPK3
Signalling to ERKs	1	601.0×	0.010	MAPKAPK3
activated TAK1 mediates p38 MAPK activation	1	496.5×	0.010	MAPKAPK3
MAP kinase activation	1	308.6×	0.010	MAPKAPK3
Interleukin-17 signaling	1	253.8×	0.010	MAPKAPK3
Signaling by VEGF	1	219.6×	0.010	MAPKAPK3
Toll Like Receptor 10 (TLR10) Cascade	1	215.5×	0.010	MAPKAPK3
Toll Like Receptor 5 (TLR5) Cascade	1	215.5×	0.010	MAPKAPK3
MyD88 cascade initiated on plasma membrane	1	203.9×	0.010	MAPKAPK3
Signaling by NTRK1 (TRKA)	1	196.9×	0.010	MAPKAPK3
Toll Like Receptor 3 (TLR3) Cascade	1	193.6×	0.010	MAPKAPK3
TRIF (TICAM1)-mediated TLR4 signaling	1	190.3×	0.010	MAPKAPK3
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	190.3×	0.010	MAPKAPK3
MyD88 dependent cascade initiated on endosome	1	190.3×	0.010	MAPKAPK3
MyD88-independent TLR4 cascade	1	184.2×	0.010	MAPKAPK3
Toll Like Receptor 7/8 (TLR7/8) Cascade	1	184.2×	0.010	MAPKAPK3
Signaling by NTRKs	1	181.3×	0.010	MAPKAPK3
Toll Like Receptor 9 (TLR9) Cascade	1	175.7×	0.010	MAPKAPK3
Toll Like Receptor TLR6:TLR2 Cascade	1	175.7×	0.010	MAPKAPK3
Toll Like Receptor 2 (TLR2) Cascade	1	173.0×	0.010	MAPKAPK3
Toll Like Receptor TLR1:TLR2 Cascade	1	167.9×	0.010	MAPKAPK3
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	152.3×	0.010	MAPKAPK3
VEGFA-VEGFR2 Pathway	1	139.3×	0.010	MAPKAPK3
Cellular Senescence	1	137.6×	0.010	MAPKAPK3
Toll Like Receptor 4 (TLR4) Cascade	1	131.3×	0.011	MAPKAPK3
Toll-like Receptor Cascades	1	124.1×	0.011	MAPKAPK3
Oxidative Stress Induced Senescence	1	90.6×	0.014	MAPKAPK3
Signaling by Interleukins	1	64.2×	0.019	MAPKAPK3
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.023	MAPKAPK3

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
macropinocytosis	1	1872.4×	0.004	MAPKAPK3
toll-like receptor signaling pathway	1	601.9×	0.005	MAPKAPK3
vascular endothelial growth factor receptor signaling pathway	1	481.5×	0.005	MAPKAPK3
response to cytokine	1	374.5×	0.005	MAPKAPK3
MAPK cascade	1	153.2×	0.010	MAPKAPK3
response to lipopolysaccharide	1	124.8×	0.011	MAPKAPK3
intracellular signal transduction	1	38.1×	0.030	MAPKAPK3
signal transduction	1	16.1×	0.062	MAPKAPK3

Therapeutics

Drug target analysis

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

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
MAPKAPK3	4	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TESEVATINIB	3	MAPKAPK3
SILMITASERTIB	2	MAPKAPK3
LAUROGUADINE	2	MAPKAPK3
BAFETINIB	2	MAPKAPK3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MAPKAPK3	239	Binding:232, Functional:7

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MAPKAPK3	239

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

4 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)
TESEVATINIB	3	MAPKAPK3
SILMITASERTIB	2	MAPKAPK3
LAUROGUADINE	2	MAPKAPK3
BAFETINIB	2	MAPKAPK3

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	1	MAPKAPK3
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.