BSCL2

Chr 11ARAD

BSCL2 lipid droplet biogenesis associated, seipin

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

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]

GeneReviewsOMIMResearchGenerating clinical summary…

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

Clinical highlights

Gene-disease validity (ClinGen)
distal hereditary motor neuropathy · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
26
Pubs (1 yr)
P/LP submissions
P/LP missense
1.01
LOEUF
LOF
Mechanism· G2P
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GeneReview available — BSCL2
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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 OE?0.68 (0.471.01)
00.351.4
Missense OE?0.95 (0.861.06)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 18 / 26.5Missense obs/exp: 248 / 259.8Syn Z: -0.45

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.