Basal laminar drusen

Summary

Basal laminar drusen (MONDO:0007472) is a disease caused by CFH (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CFH (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 480

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	basal laminar drusen
Mondo ID	MONDO:0007472
MeSH	C563034
OMIM	126700
DOID	DOID:0060746
UMLS	C0730295
MedGen	152676
GARD	0015060
Anatomy (UBERON)	UBERON:0003957
Is cancer (heuristic)	no

Also known as: basal laminar drusen · drusen of Bruch membrane

Data availability: 480 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › uveal disorder › optic choroid disorder › retinal dystrophies primarily involving Bruch’s membrane › basal laminar drusen

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

480 retrieved; paginated sample, class counts are floors:

291 uncertain significance, 51 conflicting classifications of pathogenicity, 36 benign/likely benign, 34 benign, 25 likely benign, 19 likely pathogenic, low penetrance, 7 pathogenic/likely pathogenic, 7 likely pathogenic, 6 pathogenic, 1 likely pathogenic/likely pathogenic, low penetrance, 1 pathogenic/likely pathogenic/pathogenic, low penetrance, 1 pathogenic; risk factor, 1 pathogenic/likely pathogenic, low penetrance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068249	NM_000186.4(CFH):c.157C>T (p.Arg53Cys)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1162886	NM_000186.4(CFH):c.694C>T (p.Arg232Ter)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1343348	NM_000186.4(CFH):c.740del (p.Gly247fs)	CFH	Likely pathogenic/Likely pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
1417726	NM_000186.4(CFH):c.213G>A (p.Trp71Ter)	CFH	Pathogenic/Likely pathogenic/Pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
1450348	NM_000186.4(CFH):c.1873G>T (p.Glu625Ter)	CFH	Pathogenic	criteria provided, multiple submitters, no conflicts
1452931	NM_000186.4(CFH):c.1243del (p.Ala415fs)	CFH	Pathogenic	criteria provided, multiple submitters, no conflicts
1454075	NM_000186.4(CFH):c.2602dup (p.Ile868fs)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16545	NM_000186.4(CFH):c.3572C>T (p.Ser1191Leu)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16549	NM_000186.4(CFH):c.1204= (p.His402=)	CFH	Pathogenic; risk factor	no assertion criteria provided
16560	NM_000186.4(CFH):c.1222C>T (p.Gln408Ter)	CFH	Pathogenic	criteria provided, single submitter
2025535	NM_000186.4(CFH):c.2575C>T (p.Gln859Ter)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
294526	NM_000186.4(CFH):c.3643C>T (p.Arg1215Ter)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3765465	NM_000186.4(CFH):c.619+1G>A	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4291295	NM_000186.4(CFH):c.550del (p.Ile184fs)	CFH	Pathogenic	criteria provided, single submitter
4291308	NM_000186.4(CFH):c.607_610dup (p.Lys204fs)	CFH	Pathogenic	criteria provided, single submitter
4291426	NM_000186.4(CFH):c.1833C>A (p.Cys611Ter)	CFH	Pathogenic/Likely pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
4291656	NM_000186.4(CFH):c.350+1G>T	CFH	Pathogenic	criteria provided, single submitter
1936765	NM_000186.4(CFH):c.2236+1G>C	CFH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3381091	NM_000186.4(CFH):c.1673G>A (p.Trp558Ter)	CFH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3575053	NM_000186.4(CFH):c.39G>A (p.Trp13Ter)	CFH	Likely pathogenic	criteria provided, single submitter
3575077	NM_000186.4(CFH):c.139del (p.Gln47fs)	CFH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3575166	NM_000186.4(CFH):c.336T>A (p.Tyr112Ter)	CFH	Likely pathogenic	criteria provided, single submitter
3575263	NM_000186.4(CFH):c.620-2A>G	CFH	Likely pathogenic	criteria provided, single submitter
3575324	NM_000186.4(CFH):c.1337-2A>G	CFH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4291290	NM_000186.4(CFH):c.514C>T (p.Gln172Ter)	CFH	Likely pathogenic, low penetrance	criteria provided, single submitter
4291298	NM_000186.4(CFH):c.67G>T (p.Glu23Ter)	CFH	Likely pathogenic, low penetrance	criteria provided, single submitter
4291309	NM_000186.4(CFH):c.615T>A (p.Cys205Ter)	CFH	Likely pathogenic, low penetrance	criteria provided, single submitter
4291311	NM_000186.4(CFH):c.617_618dup (p.Glu207fs)	CFH	Likely pathogenic, low penetrance	criteria provided, single submitter
4291321	NM_000186.4(CFH):c.705T>A (p.Tyr235Ter)	CFH	Likely pathogenic, low penetrance	criteria provided, single submitter
4291352	NM_000186.4(CFH):c.1056T>A (p.Tyr352Ter)	CFH	Likely pathogenic, low penetrance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 7 · 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
CFH	Strong	Autosomal dominant	basal laminar drusen	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFH	Orphanet:200421	Immunodeficiency with factor H anomaly
CFH	Orphanet:244242	HELLP syndrome
CFH	Orphanet:244275	De novo thrombotic microangiopathy after kidney transplantation
CFH	Orphanet:329903	Immunoglobulin-mediated membranoproliferative glomerulonephritis
CFH	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
CFH	Orphanet:75376	Familial drusen
CFH	Orphanet:93571	Dense deposit 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
CFH	HGNC:4883	ENSG00000000971	P08603	Complement factor H	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFH	Complement factor H	Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation.

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
Complement	1	268.0×	0.004

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFH	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med

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
calcaneal tendon	1
right coronary artery	1
urethra	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFH	267	ubiquitous	marker	urethra, calcaneal tendon, right coronary artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFH	1,844

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFH	P08603	51

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Regulation of Complement cascade	1	233.1×	0.004	CFH

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
regulation of complement activation, alternative pathway	1	8426.0×	9e-04	CFH
regulation of complement-dependent cytotoxicity	1	3370.4×	0.001	CFH
regulation of complement activation	1	2106.5×	0.001	CFH
complement activation, alternative pathway	1	991.3×	0.002	CFH
central nervous system myelination	1	991.3×	0.002	CFH
complement activation	1	624.1×	0.002	CFH
inflammatory response	1	37.7×	0.029	CFH
proteolysis	1	34.2×	0.029	CFH

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
CFH	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
CFH	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	1	CFH
D	Druggable family + AlphaFold only, no drug	0
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)
CFH	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.