FSCN2

Chr 17

fascin actin-bundling protein 2, retinal

Also known as: RFSN, RP30

NCBI Gene: 25794UniProt: O14926

This gene encodes a member of the fascin protein family. Fascins crosslink actin into filamentous bundles within dynamic cell extensions. This family member is proposed to play a role in photoreceptor disk morphogenesis. A mutation in this gene results in one form of autosomal dominant retinitis pigmentosa and macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Retinitis pigmentosa 30MIM #607921
0
Active trials
21
Pathogenic / LP
459
ClinVar variants
1
Pubs (1 yr)
-0.1
Missense Z
1.48
LOEUF
Clinical Summary— FSCN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 308 VUS of 459 total submissions
📖
GeneReview available — FSCN2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.48LOEUF
pLI 0.000
Z-score -0.04
OE 1.01 (0.70–1.48)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.11Z-score
OE missense 1.02 (0.93–1.11)
344 obs / 338.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.01 (0.70–1.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.93–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.19
0≤1.21.6
LoF obs/exp: 19 / 18.8Missense obs/exp: 344 / 338.1Syn Z: -1.82

ClinVar Variant Classifications

459 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic6
VUS308
Likely Benign98
Benign17
Conflicting15
15
Pathogenic
6
Likely Pathogenic
308
VUS
98
Likely Benign
17
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
1
1
4
0
6
VUS
13
266
25
4
308
Likely Benign
0
5
15
78
98
Benign
1
3
1
12
17
Conflicting
—15
Total152756094459

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FSCN2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

FSCN2-related retinitis pigmentosa

limited
ADLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Retinitis pigmentosa 30

MIM #607921

Molecular basis of disorder known

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autosomal dominant macular degeneration associated with 208delG mutation in the FSCN2 gene.
Wada Y et al.·Arch Ophthalmol
2003Case report
PRPF31 reduction causes ciliary defects of photoreceptors via inhibiting expression of FSCN2.
Lan Y et al.·Exp Eye Res
2026
Allelic copy number variation in FSCN2 detected using allele-specific genotyping and multiplex real-time PCRs.
Jin ZB et al.·Invest Ophthalmol Vis Sci
2008
Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity.
Obuća M et al.·PLoS One
2022
Mutation of human retinal fascin gene (FSCN2) causes autosomal dominant retinitis pigmentosa.
Wada Y et al.·Invest Ophthalmol Vis Sci
2001
Whole exome sequencing in Thai patients with retinitis pigmentosa reveals novel mutations in six genes.
Jinda W et al.·Invest Ophthalmol Vis Sci
2014Cohort
Identification of photoreceptor genes affected by PRPF31 mutations associated with autosomal dominant retinitis pigmentosa.
Mordes D et al.·Neurobiol Dis
2007
[Genetic aspects of age-related macular degeneration].
Janik-Papis K et al.·Klin Oczna
2009Review
A QTL on Chr 5 modifies hearing loss associated with the fascin-2 variant of DBA/2J mice.
Johnson KR et al.·Mamm Genome
2015
Prevalence of disease-causing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families.
Sullivan LS et al.·Invest Ophthalmol Vis Sci
2006
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Inhibition of the ILK-AKT pathway by upregulation of PARVB contributes to the cochlear cell death in Fascin2 gene knockout mice
Liu R et al.·Cell Death Discov
2024
Loss of Fascin2 increases susceptibility to cisplatin-induced hearing impairment and cochlear cell apoptosis in mice.
Wang Y et al.·J Otol
2024
Prognostic significance of FSCN family in multiple myeloma
Deng C et al.·J Cancer
2021
Comprehensive analysis of the expression, prognosis and biological significance of FSCN family in clear cell renal cell carcinoma
Lin Y et al.·Oncol Lett
2023
Deregulated Gene Expression Profiles and Regulatory Networks in Adult and Pediatric RUNX1/RUNX1T1-Positive AML Patients
Kanellou P et al.·Cancers (Basel)
2023Cohort
Growth of spiral ganglion neurons induced by graphene oxide/oxidized bacterial cellulose composite hydrogel.
Shi L et al.·Carbohydr Polym
2023
Functional assays of non-canonical splice-site variants in inherited retinal dystrophies genes
Rodriguez-Muñoz A et al.·Sci Rep
2022Functional
Mediation by DNA methylation on the association of BMI and serum uric acid in Chinese monozygotic twins.
Wang W et al.·Gene
2023
Top 8 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients