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Retinal disorders

Gene: CFI

Red List (low evidence)

CFI (complement factor I)
EnsemblGeneIds (GRCh38): ENSG00000205403
EnsemblGeneIds (GRCh37): ENSG00000205403
OMIM: 217030, Gene2Phenotype
CFI is in 7 panels

2 reviews

Ida Ertmanska (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Macular degeneration was reported in two Tunisian patients, heterozygous for a CFI variant. The reported variant is also common in healthy Tunisian controls. Hence, the gene can only be rated as Red with the current evidence.
Created: 29 Aug 2025, 8:54 a.m. | Last Modified: 29 Aug 2025, 8:54 a.m.
Panel Version: 8.14
PMID: 25986072 – Two families with carriers of CFI:c.1234G>A p.(Val412Met). 24yo heterozygous carrier Fam3-01 displayed early-onset drusen maculopathy. Individual Fam1-01, 68yo, had advanced age-related macular degeneration – time of onset unknown. 10/200 unrelated Tunisian Jewish controls were reported to carry for the variant (5% allele freq) - too high to cause the disorder. The variant is also present in gnomAD v4.1.0: highest allele freq = 0.0004954 (Middle Eastern population; no homozygotes).
OMIM reports a gene association with disease susceptibility (OMIM:615439 Macular degeneration, age related, 13, susceptibility to; accessed 20th Aug 2025).
Created: 29 Aug 2025, 8:41 a.m. | Last Modified: 29 Aug 2025, 8:41 a.m.
Panel Version: 8.14

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Macular degeneration, age related, 13, susceptibility to, OMIM:615439; retinal disorder, MONDO:0005283

Publications

Siying Lin (Moorfields Eye Hospital)

I don't know

A rare heterozygous variant in CFI was identified in two Tunisian families: one affected by early-onset drusen maculopathy and the other by “advanced AMD,” although the age of onset in the latter is unknown (PMID: 25986072). Functional studies provide evidence that rare, highly penetrant CFI variants contribute to the genetic burden of AMD (PMIDs: 25788521, 23685748), supporting a potential mechanistic link between these variants and dominantly inherited early-onset drusen maculopathy.
Sources: Literature
Created: 22 May 2025, 12:03 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Early Onset Drsen Maculopathy

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
Phenotypes
  • Macular degeneration, age related, 13, susceptibility to, OMIM:615439
  • retinal disorder, MONDO:0005283
OMIM
217030
Clinvar variants
Variants in CFI
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

29 Aug 2025, Gel status: 1

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: cfi has been classified as Red List (Low Evidence).

29 Aug 2025, Gel status: 0

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: CFI were set to

29 Aug 2025, Gel status: 0

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: CFI were changed from Early Onset Drsen Maculopathy to Macular degeneration, age related, 13, susceptibility to, OMIM:615439; retinal disorder, MONDO:0005283

22 May 2025, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set Phenotypes, Set penetrance

Siying Lin (Moorfields Eye Hospital)

gene: CFI was added gene: CFI was added to Retinal disorders. Sources: Literature Mode of inheritance for gene: CFI was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: CFI were set to Early Onset Drsen Maculopathy Penetrance for gene: CFI were set to unknown Review for gene: CFI was set to AMBER