BSCL2 Berardinelli-Seip congenital lipodystrophy 2 (seipin) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: BSCL2provided by HGNC
Official Full Name: Berardinelli-Seip congenital lipodystrophy 2 (seipin)provided by HGNC
Primary source: HGNC:15832
See related: Ensembl:ENSG00000168000; HPRD:05858; MIM:606158; Vega:OTTHUMG00000150624
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HMN5; SPG17; GNG3LG
Summary: This gene encodes the multi-pass transmembrane protein 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, Mar 2011]

Genomic context

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Location :: 11q13

Sequence :: Chromosome: 11; NC_000011.9 (62457734..62477091, complement)

See BSCL2 in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

role of seipin in human disease
Title: Seipin: from human disease to molecular mechanism.
the increased expression of seipin markedly reduced the mass of white adipose tissue and the size of adipocytes and lipid droplets
Title: Overexpression of a short human seipin/BSCL2 isoform in mouse adipose tissue results in mild lipodystrophy.
the biochemical characteristics of seipin and its mis-sense mutants
Title: Molecular characterization of seipin and its mutants: implications for seipin in triacylglycerol synthesis.
N88S seipin mutant transgenic mice develop motor neuron disease via endoplasmic reticulum stress.
Title: N88S seipin mutant transgenic mice develop features of seipinopathy/BSCL2-related motor neuron disease via endoplasmic reticulum stress.
Case Report: novel BSCL2 mutation in an Indian patient with congenital generalized lipodystrophy associated with normal intellectual ability.
Title: Congenital generalized lipodystrophy in an Indian patient with a novel mutation in BSCL2 gene.
DNA sequencing of BSCL2 was performed and a heterozygous N88S missense mutation in BSCL2 gene was detected in all three patients with distal hereditary motor neuropathy type V
Title: N88S mutation in the BSCL2 gene in a Serbian family with distal hereditary motor neuropathy type V or Silver syndrome.
study of an Italian family with a Charcot-Marie-Tooth disease type 2 phenotype with pyramidal signs; in the 3 affected siblings an S90L mutation was revealed; confirms variability of phenotypes associated with Ser90Leu mutation
Title: Seipin S90L mutation in an Italian family with CMT2/dHMN and pyramidal signs.
Japanese CGL patients with BSCL2 mutations presented with severe insulin resistance, even during infancy, prior to the development of diabetes mellitus
Title: Two Japanese infants with congenital generalized lipodystrophy due to BSCL2 mutations.
This report suggests that a different type of distal hereditary motor neuropathy could exist within one family carrying N88S mutations in BSCL2.
Title: Clincial and pathological study of distal motor neuropathy with N88S mutation in BSCL2.
These results expand the clinical spectrum of HMN and suggest a digenic inheritance of HMN in this family with a BSCL2 mutation and a chromosome 16 locus likely contributing to the phenotype.
Title: A novel 16p locus associated with BSCL2 hereditary motor neuronopathy: a genetic modifier?

Submit: New GeneRIF Correction See all (36)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Congenital generalized lipodystrophy type 2

MIM: 269700

Genetic Testing Registry

Summary from GeneReviews: Berardinelli-Seip Congenital Lipodystrophy

Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.

Diagnosis Testing

The diagnosis of BSCL is established by clinical findings including lipoatrophy affecting the trunk, limbs, and face; acromegaloid features; hepatomegaly; elevated serum concentration of triglycerides; and insulin resistance. AGPAT2 and BSCL2 are the genes in which mutations are known to cause Berardinelli-Seip congenital generalized lipodystrophy type 1 and type 2 respectively.

Genetic Counseling

BSCL is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.

References

PMID: 20301391

Distal hereditary motor neuronopathy type 5

MIM: 600794

Genetic Testing Registry

Summary from GeneReviews: GARS-Associated Axonal Neuropathy

Disease Characteristics

GARS-associated axonal neuropathy (Charcot-Marie-Tooth neuropathy type 2D/distal spinal muscular atrophy V [CMT2D/dSMA-V]) is characterized by adolescent or early-adult onset of bilateral weakness and atrophy of thenar and first dorsal interosseus muscles, sparing of the hypothenar eminence until later in the course of illness, and mild to moderate impairment of vibration sense in the hands and feet later in the disease course in a minority of individuals. The phenotype is considered the CMT2D subtype when sensory deficits (reduction of pinprick, temperature, touch, and vibration perception in a stocking and [less often] glove pattern) are present and dSMA-V when sensory deficits are absent. The lower limbs are involved in about half of affected individuals. The earliest elicited manifestations in many individuals are transient cramping and pain in the hands on exposure to cold and cramping in calf muscles on exertion.

Diagnosis Testing

The diagnosis of GARS-associated axonal neuropathy is based on clinical findings, electromyography (EMG), and molecular genetic testing of GARS, encoding glycyl-tRNA synthetase.

Genetic Counseling

GARS-associated axonal neuropathy is inherited in an autosomal dominant manner. Most individuals diagnosed with the disorder have an affected parent. The proportion of cases caused by de novo mutations is unknown. Each child of an individual with GARS-associated axonal neuropathy has a 50% chance of inheriting the mutation. Prenatal testing is possible if the disease-causing mutation has been identified in an affected family member.

References

PMID: 20301420

Summary from GeneReviews: BSCL2-Related Neurologic Disorders/Seipinopathy

Disease Characteristics

The spectrum of BSCL2-related neurologic disorders includes Silver syndrome and variants of Charcot-Marie-Tooth disease type 2, distal hereditary motor neuropathy (dHMN) type V, and spastic paraplegia 17. Features of these disorders include onset of symptoms ranging from the first to the seventh decade, slow disease progression, upper motor neuron involvement (gait disturbance with pyramidal signs ranging from mild to severe spasticity with hyperreflexia in the lower limbs and variable extensor plantar responses), lower motor neuron involvement (amyotrophy of the peroneal muscles and small muscles of the hand), abnormal vibration sense, and pes cavus and other foot deformities. Disease severity is variable among and within families.

Diagnosis Testing

The BSCL2-related neurologic disorders are diagnosed by clinical findings, electrophysiologic studies, and molecular genetic testing. Molecular genetic testing of BSCL2 detects 100% of mutations in individuals with these disorders.

Genetic Counseling

BSCL2-related neurologic disorders are inherited in an autosomal dominant manner. Each child of an individual with a BSCL2-related neurologic disorder has a 50% chance of inheriting the mutation. Penetrance is incomplete, with more than 20% of individuals with the mutation showing no clinical abnormalities or only minor clinical signs. Prenatal testing for pregnancies at increased risk is possible in families in which the disease-causing mutation is known; however, requests for prenatal testing for adult-onset disorders are not common.

References

PMID: 20301484

Spastic paraplegia 17

MIM: 270685

Genetic Testing Registry

Summary from GeneReviews: BSCL2-Related Neurologic Disorders/Seipinopathy

Disease Characteristics

The spectrum of BSCL2-related neurologic disorders includes Silver syndrome and variants of Charcot-Marie-Tooth disease type 2, distal hereditary motor neuropathy (dHMN) type V, and spastic paraplegia 17. Features of these disorders include onset of symptoms ranging from the first to the seventh decade, slow disease progression, upper motor neuron involvement (gait disturbance with pyramidal signs ranging from mild to severe spasticity with hyperreflexia in the lower limbs and variable extensor plantar responses), lower motor neuron involvement (amyotrophy of the peroneal muscles and small muscles of the hand), abnormal vibration sense, and pes cavus and other foot deformities. Disease severity is variable among and within families.

Diagnosis Testing

The BSCL2-related neurologic disorders are diagnosed by clinical findings, electrophysiologic studies, and molecular genetic testing. Molecular genetic testing of BSCL2 detects 100% of mutations in individuals with these disorders.

Genetic Counseling

BSCL2-related neurologic disorders are inherited in an autosomal dominant manner. Each child of an individual with a BSCL2-related neurologic disorder has a 50% chance of inheriting the mutation. Penetrance is incomplete, with more than 20% of individuals with the mutation showing no clinical abnormalities or only minor clinical signs. Prenatal testing for pregnancies at increased risk is possible in families in which the disease-causing mutation is known; however, requests for prenatal testing for adult-onset disorders are not common.

References

PMID: 20301484

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
Q96G97	Q9BZL3	SMIM3	HPRD	PubMed
Q96G97	Transmembrane protein 19	TMEM19	HPRD	PubMed
Q96G97	MDS032	USE1	HPRD	PubMed
BioGRID:117749	BioGRID:107271	CANX	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117749	BioGRID:200362	Hoxa1	BioGRID	PubMed	Two-hybrid
BioGRID:117749	BioGRID:124436	SMIM3	BioGRID	PubMed	Two-hybrid
BioGRID:117749	BioGRID:120555	TMEM19	BioGRID	PubMed	Two-hybrid
BioGRID:117749	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:117749	BioGRID:120952	USE1	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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Adipogenesis, organism-specific biosystem (from WikiPathways)
Adipogenesis, organism-specific biosystemThe different classess of factors involved in adipogenesis are shown. Adipogenesis is the process by which fat cells differentiate from predadipocytes to adipocytes (fat cells). Adipose tissue, compo...

General gene information

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Markers

D11S1765 (e-PCR), detects polymorphism
- UniSTS:25367

D11S4063 (e-PCR)
- UniSTS:154160

D11S4928 (e-PCR)
- UniSTS:31824

RH12537 (e-PCR)
- UniSTS:39883

G40260 (e-PCR)
- UniSTS:61688

D11S987 (e-PCR), detects polymorphism
- UniSTS:61688

D11S1084 (e-PCR)
- UniSTS:65274

RH12527 (e-PCR)
- UniSTS:58367

Genotypes

Readthrough HNRNPUL2-BSCL2

Readthrough gene: HNRNPUL2-BSCL2, Included gene: HNRNPUL2

Homology

Homologs of the BSCL2 gene: The BSCL2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

MGC4694, FLJ16651

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
molecular_function	ND No biological Data available more info

Process	Evidence Code	Pubs
biological_process	ND No biological Data available more info
cell death	IEA Inferred from Electronic Annotation more info
fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
lipid catabolic process	IEA Inferred from Electronic Annotation more info
lipid particle organization	IMP Inferred from Mutant Phenotype more info	PubMed
lipid storage	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of lipid catabolic process	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
integral to endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: seipin

Names: seipin; Bernardinelli-Seip congenital lipodystrophy type 2 protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008461.1 RefSeqGene

Range

4956..24313

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001122955.3 → NP_001116427.1 seipin isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

BC093048, BG699373, DB296305

Consensus CDS

CCDS44627.1

UniProtKB/Swiss-Prot

Q96G97

Related

ENSP00000354032, OTTHUMP00000198004, ENST00000360796, OTTHUMT00000319182

Conserved Domains (1) summary

pfam06775
Location:101 – 307
Blast Score: 634

Seipin; Putative adipose-regulatory protein (Seipin)
NM_001130702.2 → NP_001124174.2 seipin isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) has multiple differences, compared to variant 1, one of which results in a translational frameshift. The resulting protein (isoform 3) is shorter at the N-terminus and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AK027524, DB296305

Consensus CDS

CCDS55769.1

UniProtKB/Swiss-Prot

Q96G97

Related

ENSP00000278893, OTTHUMP00000198009, ENST00000278893, OTTHUMT00000319187

Conserved Domains (1) summary

pfam06775
Location:37 – 224
Blast Score: 532

Seipin; Putative adipose-regulatory protein (Seipin)
NM_032667.6 → NP_116056.3 seipin isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate 5' exon and uses a downstream AUG start codon, as compared to variant 1. The resulting isoform (2) has a shorter N-terminus, as compared to isoform 1.

Source sequence(s)

AK027524, BC041640, DB296305

Consensus CDS

CCDS8031.1

UniProtKB/Swiss-Prot

Q96G97

Related

ENSP00000384080, OTTHUMP00000198006, ENST00000407022, OTTHUMT00000319184

Conserved Domains (2) summary

pfam05395
Location:264 – 360
Blast Score: 83

DARPP-32; Protein phosphatase inhibitor 1/DARPP-32

pfam06775
Location:37 – 243
Blast Score: 616

Seipin; Putative adipose-regulatory protein (Seipin)

RNA

NR_037948.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs at the 5' end, compared to variant 1. This variant (4) is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK315423, AP001458, BP370169, DB296305
NR_037949.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs at the 5' end and uses an alternate splice site in an internal exon, compared to variant 1. This variant (5) is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AP001458, BC009866, BP370169, DB296305

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p10 Primary Assembly

Range

62457734..62477091, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

58786515..58805891, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018922.1 Alternate CHM1_1.0

Range

62378010..62397353, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01003238.1 (3290..10773)	None
genomic	ABBA01003239.1	None
genomic	ABBA01003240.1 (4303..10383)	None
genomic	AMYH01003690.1 (229227..248570)	None
genomic	AP001458.6 (97541..114613)	None
genomic	CH471076.1	EAW74070.1
		EAW74072.1
		EAW74073.1
		EAW74074.1
		EAW74075.1
		EAW74078.1
		EAW74080.1
		EAW74081.1
genomic	CQ783924.1	CAF86927.1
genomic	CS072299.1	CAI93437.1
mRNA	AF052149.1	None
mRNA	AK027524.1	BAB55175.1
mRNA	AK075317.1	BAC11543.1
mRNA	AK223606.1	BAD97326.1
mRNA	AK225029.1	None
mRNA	AK315423.1	None
mRNA	BC004911.2	AAH04911.1
mRNA	BC009866.2	None
mRNA	BC012140.1	AAH12140.1
mRNA	BC041640.1	AAH41640.1
mRNA	BC093048.1	AAH93048.1
mRNA	BG699373.1	None
mRNA	BM763152.1	None
mRNA	BP370169.1	None
mRNA	CD107822.1	None
mRNA	DB178846.1	None
mRNA	DB296305.1	None
other-genetic	DQ893483.2	ABM84409.1
other-genetic	EU176769.1	ABW03570.1