Macular dystrophy with central cone involvement
diseaseOn this page
Also known as CCMD
Summary
Macular dystrophy with central cone involvement (MONDO:0014515) is a disease caused by MFSD8 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: MFSD8 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 46
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | macular dystrophy with central cone involvement |
| Mondo ID | MONDO:0014515 |
| OMIM | 616170 |
| UMLS | C4015371 |
| MedGen | 863808 |
| GARD | 0024996 |
| Is cancer (heuristic) | no |
Also known as: CCMD · macular dystrophy with central cone involvement
Data availability: 46 ClinVar variants · 1 GenCC gene-disease record.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › degeneration of macula and posterior pole › age-related macular degeneration › macular dystrophy with central cone involvement
Related subtypes (14): wet macular degeneration, age related macular degeneration 2, age related macular degeneration 1, macular degeneration, age-related, 3, age related macular degeneration 7, age related macular degeneration 4, age related macular degeneration 9, age related macular degeneration 10, age related macular degeneration 11, age related macular degeneration 6, age related macular degeneration 8, age related macular degeneration 12, age related macular degeneration 14, dry age related macular degeneration
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
46 retrieved; paginated sample, class counts are floors:
12 uncertain significance, 10 pathogenic/likely pathogenic, 10 likely pathogenic, 6 pathogenic, 5 benign/likely benign, 3 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1003 | NM_001371596.2(MFSD8):c.894T>G (p.Tyr298Ter) | MFSD8 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1005 | NM_001371596.2(MFSD8):c.1235C>T (p.Pro412Leu) | MFSD8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1067690 | NM_001371596.2(MFSD8):c.864-1G>A | MFSD8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1373124 | NM_001371596.2(MFSD8):c.77T>G (p.Leu26Ter) | MFSD8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 162379 | NM_001371596.2(MFSD8):c.1141G>T (p.Glu381Ter) | MFSD8 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 162380 | NM_001371596.2(MFSD8):c.1102G>C (p.Asp368His) | MFSD8 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 162382 | NM_001371596.2(MFSD8):c.1444C>T (p.Arg482Ter) | MFSD8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1895455 | NM_001371596.2(MFSD8):c.698+2T>A | MFSD8 | Pathogenic | criteria provided, single submitter |
| 206175 | NM_001371596.2(MFSD8):c.217dup (p.Thr73fs) | MFSD8 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3590143 | NM_001371596.2(MFSD8):c.910C>T (p.Gln304Ter) | MFSD8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 418295 | NM_001371596.2(MFSD8):c.1361T>C (p.Met454Thr) | MFSD8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 504403 | NM_001371596.2(MFSD8):c.553+1G>A | MFSD8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 65897 | NM_001371596.2(MFSD8):c.754+2T>A | MFSD8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 802088 | NM_001371596.2(MFSD8):c.1124del (p.Pro375fs) | MFSD8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 846459 | NM_001371596.2(MFSD8):c.103C>T (p.Arg35Ter) | MFSD8 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 872266 | NM_001371596.2(MFSD8):c.754+1G>A | MFSD8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1048170 | NM_001371596.2(MFSD8):c.670A>T (p.Asn224Tyr) | MFSD8 | Likely pathogenic | criteria provided, single submitter |
| 2151991 | NM_001371596.2(MFSD8):c.154+1G>A | MFSD8 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3336668 | NM_001371596.2(MFSD8):c.193C>T (p.Gln65Ter) | MFSD8 | Likely pathogenic | criteria provided, single submitter |
| 3590141 | NM_001371596.2(MFSD8):c.1436G>A (p.Trp479Ter) | MFSD8 | Likely pathogenic | criteria provided, single submitter |
| 3590142 | NM_001371596.2(MFSD8):c.1102G>A (p.Asp368Asn) | MFSD8 | Likely pathogenic | criteria provided, single submitter |
| 3590144 | NM_001371596.2(MFSD8):c.698+1G>A | MFSD8 | Likely pathogenic | criteria provided, single submitter |
| 3590145 | NM_001371596.2(MFSD8):c.472G>A (p.Gly158Ser) | MFSD8 | Likely pathogenic | criteria provided, single submitter |
| 3590146 | NM_001371596.2(MFSD8):c.198+2T>G | MFSD8 | Likely pathogenic | criteria provided, single submitter |
| 3590147 | NM_001371596.2(MFSD8):c.28C>T (p.Gln10Ter) | MFSD8 | Likely pathogenic | criteria provided, single submitter |
| 3590148 | NM_001371596.2(MFSD8):c.25G>T (p.Glu9Ter) | MFSD8 | Likely pathogenic | criteria provided, single submitter |
| 162378 | NM_001371596.2(MFSD8):c.1006G>C (p.Glu336Gln) | MFSD8 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 206153 | NM_001371596.2(MFSD8):c.677T>C (p.Ile226Thr) | MFSD8 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 431131 | NM_001371596.2(MFSD8):c.416G>A (p.Arg139His) | MFSD8 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 206147 | NM_001371596.2(MFSD8):c.343G>A (p.Val115Met) | MFSD8 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 7 · Orphanet: 2 · 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 |
|---|---|---|---|---|
| MFSD8 | Strong | Autosomal recessive | macular dystrophy with central cone involvement | 7 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| MFSD8 | Orphanet:1872 | Cone rod dystrophy |
| MFSD8 | Orphanet:228366 | CLN7 disease |
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 |
|---|---|---|---|---|---|
| MFSD8 | HGNC:28486 | ENSG00000164073 | Q8NHS3 | Major facilitator superfamily domain-containing protein 8 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| MFSD8 | Major facilitator superfamily domain-containing protein 8 | Outward-rectifying chloride channel involved in endolysosomal chloride homeostasis, membrane fusion and function. |
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 |
|---|---|---|---|
| Transporter | 1 | 77.8× | 0.013 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| MFSD8 | Transporter | yes | MFS, MFS_dom, MFS_trans_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 |
|---|---|
| adrenal tissue | 1 |
| calcaneal tendon | 1 |
| oviduct epithelium | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| MFSD8 | 256 | ubiquitous | marker | oviduct epithelium, adrenal tissue, calcaneal tendon |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| MFSD8 | 1,405 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| MFSD8 | Q8NHS3 | 83.20 |
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 |
|---|---|---|---|---|
| maintenance of location | 1 | 16852.0× | 1e-03 | MFSD8 |
| glycolipid metabolic process | 1 | 8426.0× | 1e-03 | MFSD8 |
| inclusion body assembly | 1 | 8426.0× | 1e-03 | MFSD8 |
| regulation of lysosomal protein catabolic process | 1 | 5617.3× | 0.001 | MFSD8 |
| microglia differentiation | 1 | 1532.0× | 0.003 | MFSD8 |
| glycoprotein metabolic process | 1 | 1123.5× | 0.003 | MFSD8 |
| lysosomal protein catabolic process | 1 | 1053.2× | 0.003 | MFSD8 |
| TORC1 signaling | 1 | 802.5× | 0.004 | MFSD8 |
| astrocyte differentiation | 1 | 766.0× | 0.004 | MFSD8 |
| motor behavior | 1 | 561.7× | 0.004 | MFSD8 |
| neuromuscular process | 1 | 526.6× | 0.004 | MFSD8 |
| reactive oxygen species metabolic process | 1 | 468.1× | 0.004 | MFSD8 |
| determination of adult lifespan | 1 | 432.1× | 0.004 | MFSD8 |
| glycolytic process | 1 | 383.0× | 0.005 | MFSD8 |
| autophagosome maturation | 1 | 351.1× | 0.005 | MFSD8 |
| lysosome organization | 1 | 306.4× | 0.005 | MFSD8 |
| neuron development | 1 | 255.3× | 0.005 | MFSD8 |
| retina development in camera-type eye | 1 | 255.3× | 0.005 | MFSD8 |
| regulation of autophagy | 1 | 240.7× | 0.005 | MFSD8 |
| neuron apoptotic process | 1 | 185.2× | 0.007 | MFSD8 |
| mitochondrion organization | 1 | 151.8× | 0.008 | MFSD8 |
| multicellular organism growth | 1 | 137.0× | 0.008 | MFSD8 |
| negative regulation of neuron apoptotic process | 1 | 110.9× | 0.010 | MFSD8 |
| gene expression | 1 | 79.9× | 0.013 | MFSD8 |
| protein stabilization | 1 | 66.9× | 0.015 | MFSD8 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| MFSD8 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
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 | 1 | MFSD8 |
| E | Difficult family or no structure, no drug | 0 |
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) |
|---|---|---|
| MFSD8 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: MFSD8