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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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FSCN2
fascin actin-bundling protein 2, retinal
Chromosome 17 Β· 17q25.3
NCBI Gene: 25794Ensembl: ENSG00000186765.12HGNC: HGNC:3960UniProt: O14926
32PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingactin bindingactin filament bindingestablishment or maintenance of cell polarityretinitis pigmentosaRetinal dystrophyhearing lossmacular degeneration
✦AI Summary

FSCN2 encodes retinal fascin, a photoreceptor-specific actin-bundling protein that cross-links F-actin into highly ordered bundles 1. The protein is essential for photoreceptor disk morphogenesis and maintaining the structural integrity of photoreceptor outer segments 1. FSCN2 is also localized in stereocilia of hair cells, where it maintains auditory function 2. Mutations in FSCN2 cause autosomal dominant retinitis pigmentosa (ADRP), with the 208delG mutation identified in 3.3% of Japanese ADRP patients 3. The same mutation produces phenotypic variability, also causing autosomal dominant macular degeneration in some families 4. A novel missense mutation (p.Pro406Leu) has been associated with cone dystrophy featuring central ellipsoid zone loss 5. Mouse models with FSCN2 mutations demonstrate progressive photoreceptor degeneration with structural abnormalities of outer segment disks and depressed electroretinogram responses, suggesting haploinsufficiency mechanisms 6. Beyond vision, null mutations in Fscn2 cause progressive hearing loss in mice through hair cell degeneration and stereocilia loss 2. Large-scale sequencing studies identified rare FSCN2 coding variants associated with adult hearing loss 7, establishing the gene's role in both visual and auditory systems.

Sources cited
1
FSCN2 encodes photoreceptor-specific actin-bundling protein; function in disk morphogenesis and gene structure/localization
PMID: 10783262
2
208delG mutation causes autosomal dominant retinitis pigmentosa; prevalence of 3.3% in Japanese ADRP patients
PMID: 11527955
3
FSCN2 mutations cause progressive photoreceptor degeneration with outer segment abnormalities and depressed ERG responses
PMID: 16043865
4
Novel FSCN2 mutation (p.Pro406Leu) associated with cone dystrophy and central ellipsoid zone loss
PMID: 29016529
5
FSCN2 localization in stereocilia; null mutations cause progressive hearing loss and hair cell degeneration; retinal thinning in mice
PMID: 30082328
6
208delG mutation produces phenotypic variability including both retinitis pigmentosa and autosomal dominant macular degeneration
PMID: 14609921
7
Rare FSCN2 coding variants associated with adult hearing loss in large-scale exome sequencing
PMID: 35661827
Disease Associationsβ“˜21
retinitis pigmentosaOpen Targets
0.53Moderate
Retinal dystrophyOpen Targets
0.39Weak
hearing lossOpen Targets
0.38Weak
macular degenerationOpen Targets
0.34Weak
age-related hearing impairmentOpen Targets
0.28Weak
Sensorineural hearing impairmentOpen Targets
0.18Weak
Meniere diseaseOpen Targets
0.16Weak
ankylosing spondylitisOpen Targets
0.13Weak
Leber congenital amaurosisOpen Targets
0.12Weak
X-linked retinal dysplasiaOpen Targets
0.07Suggestive
Stargardt diseaseOpen Targets
0.07Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.07Suggestive
Cone rod dystrophyOpen Targets
0.07Suggestive
Familial drusenOpen Targets
0.07Suggestive
deafnessOpen Targets
0.07Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.06Suggestive
Sorsby's fundus dystrophyOpen Targets
0.06Suggestive
age-related macular degenerationOpen Targets
0.06Suggestive
Sorsby fundus dystrophyOpen Targets
0.06Suggestive
X-linked retinoschisisOpen Targets
0.06Suggestive
Retinitis pigmentosa 30UniProt
Pathogenic Variants3
NM_012418.4(FSCN2):c.22C>T (p.Gln8Ter)Likely pathogenic
Retinal dystrophy
β˜…β˜†β˜†β˜†2023β†’ Residue 8
NM_001077182.3(FSCN2):c.827-1delGLikely pathogenic
Retinal dystrophy
β˜…β˜†β˜†β˜†2023
NM_012418.4(FSCN2):c.1415G>C (p.Gly472Ala)Likely pathogenic
Retinal dystrophy
β˜…β˜†β˜†β˜†2023β†’ Residue 472
View on ClinVar β†—
Related Genes
TPRNProtein interaction100%EZRProtein interaction97%GRXCR2Protein interaction93%EYSProtein interaction86%CA4Protein interaction85%PCAREProtein interaction84%
Tissue Expression6 tissues
Ovary
100%
Lung
55%
Heart
27%
Brain
26%
Liver
16%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
FSCN2TPRNEZRGRXCR2EYSCA4PCARE
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O14926
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.78LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.40 [1.11–1.78]
RankingsWhere FSCN2 stands among ~20K protein-coding genes
  • #11,518of 20,598
    Most Researched32
  • #4,108of 5,498
    Most Pathogenic Variants3
  • #16,476of 17,882
    Most Constrained (LOEUF)1.78
Genes detectedFSCN2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301590
1.00
2
Characterization of human retinal fascin gene (FSCN2) at 17q25: close physical linkage of fascin and cytoplasmic actin genes.
PMID: 10783262
Genomics Β· 2000
0.90
3
Mutation of human retinal fascin gene (FSCN2) causes autosomal dominant retinitis pigmentosa.
PMID: 11527955
Invest Ophthalmol Vis Sci Β· 2001
0.80
4
Targeted disruption of FSCN2 gene induces retinopathy in mice.
PMID: 16043865
Invest Ophthalmol Vis Sci Β· 2005
0.70
5
NOVEL CONE DYSTROPHY WITH CENTRAL ELLIPSOID ZONE LOSS ASSOCIATED WITH HUMAN RETINAL FASCIN GENE (FSCN2) MUTATION.
PMID: 29016529
Retin Cases Brief Rep Β· 2018
0.60