Larsen syndrome: genes and variants
Larsen syndrome is linked to 1 analyzed protein (FLNB). 12 DNA variants are known to cause it; 25 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Larsen syndrome
FLNB: Filamin-B
It crosslinks actin and organizes cytoskeletal signaling in cartilage, bone, and other tissues during development. Pathogenic variants cause a broad skeletal-dysplasia spectrum including atelosteogenesis, Larsen syndrome, and spondylocarpotarsal syndrome.
12 disease-causing and 25 uncertain variants in FLNB are linked to Larsen syndrome.
Where Larsen syndrome variants cluster
- FLNB Filamin 14 (positions 1512–1608): 4 of 12 disease-causing changes, 8.9× more than its size predicts.
- FLNB Filamin 15 (positions 1609–1704): 3 of 12 disease-causing changes, 6.8× more than its size predicts.
- FLNB Calponin-homology (CH) 2 (positions 139–242): 3 of 12 disease-causing changes, 6.2× more than its size predicts.
Known disease-causing variants in Larsen syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| FLNB G1691S | 1691 | Filamin 15 | Disease-causing (★★) |
| FLNB G1691D | 1691 | Filamin 15 | Disease-causing (★★) |
| FLNB E227K | 227 | Calponin-homology (CH) 2 | Disease-causing (★★) |
| FLNB G361D | 361 | Filamin 2 | Disease-causing (★★) |
| FLNB N164K | 164 | Calponin-homology (CH) 2 | Disease-causing (★) |
| FLNB N197K | 197 | Calponin-homology (CH) 2 | Disease-causing (★) |
| FLNB A1517D | 1517 | Filamin 14 | Disease-causing (★) |
| FLNB G1524S | 1524 | Filamin 14 | Disease-causing (★) |
| FLNB A1643V | 1643 | Filamin 15 | Disease-causing (★) |
| FLNB S1535N | 1535 | Filamin 14 | Disease-causing (★) |
| FLNB G1586R | 1586 | Filamin 14 | Disease-causing |
| FLNB G1834R | 1834 | Filamin 17 | Disease-causing |
Which prediction tools work for Larsen syndrome
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 78 out of 100
Same protein, different disease
- Atelosteogenesis type I is also caused by FLNB variants; they fall mostly in different places as the Larsen syndrome variants (6 disease-causing).
Diseases related to Larsen syndrome
- Connective tissue disorder, also linked to FLNB
- Atelosteogenesis type I, also linked to FLNB
- Boomerang dysplasia, also linked to FLNB
- Spondylocarpotarsal synostosis syndrome, also linked to FLNB
Frequently asked questions
Which genes are linked to Larsen syndrome?
In CATVariant, Larsen syndrome is linked to 1 analyzed protein: FLNB (Filamin-B).
How many genetic variants are linked to Larsen syndrome?
54 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 25 are of uncertain significance or have conflicting reports.
Which uncertain variants in Larsen syndrome look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Larsen syndrome?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.78, based on 12 disease-causing and 155 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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