BSCL2

Chr 11ARAD

BSCL2 lipid droplet biogenesis associated, seipin

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

NCBI Gene: 26580ENSG00000168000UniProt: Q96G97

This gene encodes the multi-pass transmembrane protein seipin. This protein localizes to the endoplasmic reticulum and may be important for lipid droplet morphology. Mutations in this gene have been associated with congenital generalized lipodystrophy type 2 or Berardinelli-Seip syndrome, a rare autosomal recessive disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Naturally occurring read-through transcription occurs between this locus and the neighboring locus HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2).[provided by RefSeq, Jul 2024]

Primary Disease Associations & Inheritance

Encephalopathy, progressive, with or without lipodystrophyMIM #615924
AR
Lipodystrophy, congenital generalized, type 2MIM #269700
AR
Neuronopathy, distal hereditary motor, autosomal dominant 13MIM #619112
AD
Silver spastic paraplegia syndromeMIM #270685
AD
585
ClinVar variants
64
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— BSCL2
🧬
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.
📋
ClinVar Variants
64 Pathogenic / Likely Pathogenic· 290 VUS of 585 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
1.01LOEUF
pLI 0.000
Z-score 1.53
OE 0.68 (0.47–1.01)
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.
0.26Z-score
OE missense 0.95 (0.86–1.06)
248 obs / 259.8 exp
Tolerant

Mild missense constraint

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.0.68 (0.47–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.86–1.06)
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.1.06
0≤1.21.6
LoF obs/exp: 18 / 26.5Missense obs/exp: 248 / 259.8Syn Z: -0.45

ClinVar Variant Classifications

585 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic21
VUS290
Likely Benign171
Benign14
Conflicting46
43
Pathogenic
21
Likely Pathogenic
290
VUS
171
Likely Benign
14
Benign
46
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
3
21
2
43
Likely Pathogenic
13
2
5
1
21
VUS
9
245
30
6
290
Likely Benign
1
15
79
76
171
Benign
0
2
12
0
14
Conflicting
—46
Total4026714785585

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

View 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.

Gene2Phenotype Curations

BSCL2-related lipodystrophy, congenital generalised

definitive
ARLoss Of FunctionAbsent Gene Product
Skin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
BSCL2 GENE; BSCL2
MIM #606158 · *

Encephalopathy, progressive, with or without lipodystrophy

MIM #615924

Molecular basis of disorder known

Autosomal recessive

Lipodystrophy, congenital generalized, type 2

MIM #269700

Molecular basis of disorder known

Autosomal recessive

Neuronopathy, distal hereditary motor, autosomal dominant 13

MIM #619112

Molecular basis of disorder known

Autosomal dominant

Silver spastic paraplegia syndrome

MIM #270685

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — BSCL2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Distal hereditary motor neuropathies.
Tazir M et al.·Rev Neurol (Paris)
2024Review
Function of seipin: new insights from Bscl2/seipin knockout mouse models.
Dollet L et al.·Biochimie
2014Review
Whole-exome sequencing analysis identifies risk genes for schizophrenia.
Chick SL et al.·Nat Commun
2025
The genetic and clinical spectrum in a cohort of 39 families with complex inherited peripheral neuropathies.
Wang M et al.·J Neurol
2023Cohort
[Primary lipodystrophies].
Capeau J et al.·Ann Endocrinol (Paris)
2007
Features of BSCL2 related congenital generalized lipodystrophy in China: long-term follow-up of three patients and literature review.
Su X et al.·J Pediatr Endocrinol Metab
2022Review
Clinical and Molecular Characterization of BSCL2 Mutations in a Taiwanese Cohort with Hereditary Neuropathy.
Hsiao CT et al.·PLoS One
2016Cohort
Identification of genetic suppressors for a BSCL2 lipodystrophy pathogenic variant in Caenorhabditis elegans.
Bai X et al.·Dis Model Mech
2024
Ablation of Bscl2/seipin in hepatocytes does not cause metabolic dysfunction in congenital generalised lipodystrophy.
Mcilroy GD et al.·Dis Model Mech
2020
Clinical features of inherited neuropathy with BSCL2 mutations in Japan.
Ishihara S et al.·J Peripher Nerv Syst
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Lipodystrophy (Genetic or Acquired, Non HIV)

The LD Lync Study - Natural History Study of Lipodystrophy Syndromes

RECRUITING
NCT03087253University of MichiganStarted 2018-02-27

External Resources

Links to major genomics databases and tools