FSCN1

Chr 7

fascin actin-bundling protein 1

Also known as: HSN, SNL, p55

NCBI Gene: 6624 ENSG00000075618 UniProt: Q16658 OMIM: 602689

The FSCN1 protein organizes actin filaments into parallel bundles and is essential for cell motility, migration, and formation of cellular protrusions including filopodia. Mutations cause autosomal recessive retinal dystrophy with early childhood onset, affecting vision and retinal function. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely poorly tolerated.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the fascin family of actin-binding proteins. Fascin proteins organize F-actin into parallel bundles, and are required for the formation of actin-based cellular protrusions. The encoded protein plays a critical role in cell migration, motility, adhesion and cellular interactions. Expression of this gene is known to be regulated by several microRNAs, and overexpression of this gene may play a role in the metastasis of multiple types of cancer by increasing cell motility. Expression of this gene is also a marker for Reed-Sternberg cells in Hodgkin's lymphoma. A pseudogene of this gene is located on the long arm of chromosome 15. [provided by RefSeq, Sep 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.41

Clinical Summary— FSCN1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.

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ClinVar Variants

64 VUS of 71 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.869

Z-score 3.17

OE 0.13 (0.05–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.98Z-score

OE missense 0.69 (0.62–0.77)

224 obs / 324.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.05–0.41)

0≤0.351.4

Missense OE?0.69 (0.62–0.77)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 2 / 15.4Missense obs/exp: 224 / 324.5Syn Z: -0.25

This gene — mechanism propensity

0.3991th %ile

GOF

0.4282th %ile

LOF

0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.41

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

71 submitted variants in ClinVar

ClinVar

Classification Summary

VUS64

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	64	0	64
Likely Benign	2	1	3
Benign	0	0	0
Total	66	1	67

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

View in ClinVar →

50 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap FSCN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →