BSCL2

Chr 11ARAD

BSCL2 lipid droplet biogenesis associated, seipin

Also known as: GNG3LG, HMN5, HMN5C, HMND13, PELD, SPG17

Seipin is an endoplasmic reticulum transmembrane protein that plays a crucial role in lipid droplet formation and maturation, which are essential for lipid and energy homeostasis. Mutations cause a spectrum of disorders including congenital generalized lipodystrophy type 2 (Berardinelli-Seip syndrome), progressive encephalopathy with or without lipodystrophy, distal hereditary motor neuronopathy, and Silver spastic paraplegia syndrome. The gene shows both autosomal recessive and autosomal dominant inheritance patterns depending on the specific condition.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 1.014 OMIM phenotypes
Clinical SummaryBSCL2
🧬
Gene-Disease Validity (ClinGen)
distal hereditary motor neuropathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.000
Z-score 1.53
OE 0.68 (0.471.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.26Z-score
OE missense 0.95 (0.861.06)
248 obs / 259.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.471.01)
00.351.4
Missense OE0.95 (0.861.06)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 18 / 26.5Missense obs/exp: 248 / 259.8Syn Z: -0.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBSCL2-related lipodystrophy, congenital generalisedLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6356th %ile
GOF
0.6345th %ile
LOF
0.3259th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

GOFIto and Suzuki (2007) concluded that the N88S and S90L mutations, which result in motor neuron disease, have a gain-of-function effect, resulting in conformational protein changes, activation of the unfolded protein response, cell death, and neurodegeneration.PMID:18585921

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BSCL2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Distal hereditary motor neuropathies.
Tazir M et al.·Rev Neurol (Paris)
2024Review
Celia's Encephalopathy (BSCL2-Gene-Related): Current Understanding.
Sánchez-Iglesias S et al.·J Clin Med
2021Review
Neonatal diabetes mellitus around the world: Update 2024.
Barbetti F et al.·J Diabetes Investig
2024Review
Top 5 results · since 2015Search PubMed ↗