BSCL2

BSCL2 lipid droplet biogenesis associated, seipin

Basic information

Region (hg38): 11:62689289-62709845

Previous symbols: [ "GNG3LG", "SPG17" ]

Links

ENSG00000168000 ∙ NCBI:26580 ∙ OMIM:606158 ∙ HGNC:15832 ∙ Uniprot:Q96G97 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neonatal diabetes mellitus (Strong), mode of inheritance: AR
• generalized lipodystrophy (Strong), mode of inheritance: AR
• congenital generalized lipodystrophy type 2 (Strong), mode of inheritance: AR
• Berardinelli-Seip congenital lipodystrophy (Supportive), mode of inheritance: AR
• hereditary spastic paraplegia 17 (Supportive), mode of inheritance: AD
• neuronopathy, distal hereditary motor, type 5A (Supportive), mode of inheritance: AD
• severe neurodegenerative syndrome with lipodystrophy (Supportive), mode of inheritance: AR
• hereditary spastic paraplegia 17 (Strong), mode of inheritance: AD
• congenital generalized lipodystrophy type 2 (Strong), mode of inheritance: AR
• severe neurodegenerative syndrome with lipodystrophy (Strong), mode of inheritance: AR
• neuronopathy, distal hereditary motor, type 5C (Strong), mode of inheritance: AD
• distal hereditary motor neuropathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lipodystrophy, congenital generalized, type 2; Encephalopathy, progressive, with or without lipodystrophy	AR	Cardiovascular; Endocrine	Dietary measures (eg, restriction of fat intake) and medications (eg, leptin) may be beneficial; Individuals may have cardiomyopathy, and surveillance and early medical management may be beneficial	Cardiovascular; Endocrine; Neurologic	5964029; 10908191; 14602785; 12362029; 14981520; 15732094; 16427281; 17671040; 19396477; 19041432; 21126715; 20301391; 23142943; 23564749

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BSCL2 gene.

• Charcot-Marie-Tooth disease type 2 (17 variants)
• Berardinelli-Seip congenital lipodystrophy (13 variants)
• Congenital generalized lipodystrophy type 2 (12 variants)
• not provided (4 variants)
• Neuronopathy, distal hereditary motor, type 5C (3 variants)
• Severe neurodegenerative syndrome with lipodystrophy (2 variants)
• Inborn genetic diseases (2 variants)
• Hereditary spastic paraplegia 17 (2 variants)
• not specified (1 variants)
• Monogenic diabetes (1 variants)
• Neuronopathy, distal hereditary motor, type 5A (1 variants)
• Peripheral neuropathy (1 variants)
• Hereditary spastic paraplegia (1 variants)
• Charcot-Marie-Tooth disease (1 variants)
• Congenital generalized lipodystrophy type 2;Neuronopathy, distal hereditary motor, type 5C;Severe neurodegenerative syndrome with lipodystrophy;Hereditary spastic paraplegia 17 (1 variants)
• Neuronopathy, distal hereditary motor, type 5C;Congenital generalized lipodystrophy type 2;Hereditary spastic paraplegia 17;Severe neurodegenerative syndrome with lipodystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BSCL2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	85	1	89
missense	3	3	210	3	1	220
nonsense	7		2			9
start loss			2			2
frameshift	12	3	1			16
inframe indel			8			8
splice donor/acceptor (+/-2bp)	2	7	1			10
splice region			18	18		36
non coding		1	8	60	16	85
Total	24	14	235	148	18

Highest pathogenic variant AF is 0.0000197

Variants in BSCL2

This is a list of pathogenic ClinVar variants found in the BSCL2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-62690309-C-T		Congenital generalized lipodystrophy type 2 • Neuronopathy, distal hereditary motor, type 5A	Uncertain significance (Jan 13, 2018)
11-62690318-A-C		Neuronopathy, distal hereditary motor, type 5A • Congenital generalized lipodystrophy type 2	Uncertain significance (Jan 12, 2018)
11-62690369-AGGAACTAGAGCAGGTGGGGCGCTGTC-A		Charcot-Marie-Tooth disease type 2	Pathogenic (Sep 25, 2023)
11-62690371-G-T		Neuronopathy, distal hereditary motor, type 5C;Severe neurodegenerative syndrome with lipodystrophy;Congenital generalized lipodystrophy type 2;Hereditary spastic paraplegia 17	Uncertain significance (Aug 02, 2021)
11-62690377-G-A			Uncertain significance (Jan 24, 2024)
11-62690380-C-G		Inborn genetic diseases	Uncertain significance (Feb 02, 2022)
11-62690380-C-T		Charcot-Marie-Tooth disease type 2	Uncertain significance (Sep 07, 2022)
11-62690382-G-A		Charcot-Marie-Tooth disease type 2	Likely benign (May 09, 2018)
11-62690383-G-A		Charcot-Marie-Tooth disease type 2	Uncertain significance (Sep 29, 2019)
11-62690385-G-T		Charcot-Marie-Tooth disease type 2	Likely benign (Mar 26, 2023)
11-62690387-G-A			Uncertain significance (Mar 01, 2017)
11-62690388-G-A		Charcot-Marie-Tooth disease type 2	Likely benign (Dec 13, 2020)
11-62690389-C-T		Monogenic diabetes • Charcot-Marie-Tooth disease type 2 • Hereditary spastic paraplegia • Congenital generalized lipodystrophy type 2 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 21, 2023)
11-62690395-C-A			Uncertain significance (Aug 22, 2016)
11-62690395-C-T		Charcot-Marie-Tooth disease type 2	Uncertain significance (Dec 19, 2023)
11-62690396-G-A		Severe neurodegenerative syndrome with lipodystrophy • Charcot-Marie-Tooth disease type 2	Conflicting classifications of pathogenicity (Feb 11, 2023)
11-62690397-G-C		Charcot-Marie-Tooth disease type 2	Likely benign (May 13, 2021)
11-62690402-C-A		Charcot-Marie-Tooth disease type 2 • BSCL2-related Developmental and epileptic encephalopathy • Inborn genetic diseases	Uncertain significance (Nov 05, 2023)
11-62690404-C-G		Charcot-Marie-Tooth disease type 2	Uncertain significance (Nov 17, 2023)
11-62690415-T-C		Charcot-Marie-Tooth disease type 2	Likely benign (Aug 21, 2022)
11-62690426-C-T		Charcot-Marie-Tooth disease type 2 • Inborn genetic diseases	Uncertain significance (Oct 08, 2021)
11-62690431-G-A			Uncertain significance (Dec 24, 2015)
11-62690436-T-C		Charcot-Marie-Tooth disease type 2	Likely benign (May 14, 2022)
11-62690439-G-T		PPARG-related familial partial lipodystrophy • Inborn genetic diseases	Likely benign (Jul 11, 2019)
11-62690441-C-T		Inborn genetic diseases	Uncertain significance (May 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BSCL2	protein_coding	protein_coding	ENST00000433053	11	19571

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.10e-9	0.765	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.260	248	260	0.955	0.0000160	2949
Missense in Polyphen		56	80.224	0.69805		894
Synonymous	-0.450	110	104	1.06	0.00000662	960
Loss of Function	1.53	18	26.5	0.680	0.00000153	285

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000362	0.000362
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000598	0.000598
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000125	0.000123
Middle Eastern	0.000598	0.000598
South Asian	0.000263	0.000261
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Is a regulator of lipid catabolism essential for adipocyte differentiation. May also be involved in the central regulation of energy homeostasis (By similarity). Necessary for correct lipid storage and lipid droplets maintenance; may play a tissue-autonomous role in controlling lipid storage in adipocytes and in preventing ectopic lipid droplet formation in non-adipose tissues. {ECO:0000250, ECO:0000269|PubMed:19278620, ECO:0000269|PubMed:21533227}.
• Disease: DISEASE: Spastic paraplegia 17, autosomal dominant (SPG17) [MIM:270685]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG17 is characterized by prominent amyotrophy of the hand muscles, the presence of mild to severe pyramidal tract signs and spastic paraplegia. SPG17 is a motor neuron disease overlapping with distal spinal muscular atrophy type 5. {ECO:0000269|PubMed:14981520, ECO:0000269|PubMed:17663003, ECO:0000269|PubMed:18585921, ECO:0000269|PubMed:24604904}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Neuronopathy, distal hereditary motor, 5A (HMN5A) [MIM:600794]: A disorder characterized by distal muscular atrophy mainly affecting the upper extremities, in contrast to other distal motor neuronopathies. These constitute a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:14981520, ECO:0000269|PubMed:17663003}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Encephalopathy, progressive, with or without lipodystrophy (PELD) [MIM:615924]: A neurodegenerative disease characterized by developmental regression of motor and cognitive skills in the first years of life, often leading to death in the first decade, hyperactive behavior, seizures, tremor and ataxic gait. Patients may show a mild or typical lipodystrophic appearance. {ECO:0000269|PubMed:23564749}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Adipogenesis (Consensus)

Intolerance Scores

• loftool: 0.0708
• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.36

Haploinsufficiency Scores

• pHI: 0.0775
• hipred: N
• hipred_score: 0.328
• ghis: 0.543

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.912

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Bscl2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: lipid catabolic process;lipid storage;lipid droplet organization;fat cell differentiation;negative regulation of lipid catabolic process;positive regulation of cold-induced thermogenesis
• Cellular component: integral component of endoplasmic reticulum membrane
• Molecular function: molecular_function;protein binding