Seipin
Function
Plays a crucial role in the formation of lipid droplets (LDs) which are storage organelles at the center of lipid and energy homeostasis (PubMed:19278620, PubMed:21533227, PubMed:30293840, PubMed:31708432). In association with LDAF1, defines the sites of LD formation in the ER (PubMed:31708432). Also required for growth and maturation of small nascent LDs into larger mature LDs (PubMed:27564575). Mediates the formation and/or stabilization of endoplasmic reticulum-lipid droplets (ER-LD) contacts, facilitating protein and lipid delivery from the ER into growing LDs (PubMed:27879284, PubMed:31178403). Regulates the maturation of ZFYVE1-positive nascent LDs and the function of the RAB18-ZFYVE1 complex in mediating the formation of ER-LD contacts (PubMed:30970241). Binds anionic phospholipids including phosphatidic acid (PubMed:30293840). Plays an important role in the differentiation and development of adipocytes (By similarity).
Involvement in disease
Lipodystrophy, congenital generalized, 2
CGL2
A form of congenital generalized lipodystrophy, a metabolic disorder characterized by a near complete absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes. Inheritance is autosomal recessive.
None
The disease is caused by variants affecting the gene represented in this entry.
Spastic paraplegia 17, autosomal dominant
SPG17
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Neuronopathy, distal hereditary motor, autosomal dominant 13
HMND13
A form of distal hereditary motor neuronopathy, 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. HMND13 is characterized by distal muscular atrophy primarily affecting the upper limbs. Lower limb involvement may occur at the same time or later. Clinical features are highly variable even within families, and include poor fine hand motor skills, difficulty walking, foot deformities, spasticity and hyperreflexia. Some HMND13 patients show axonal peripheral neuropathy and distal sensory impairment. HMND13 inheritance is autosomal dominant with incomplete penetrance.
None
The disease is caused by variants affecting the gene represented in this entry.
Encephalopathy, progressive, with or without lipodystrophy
PELD
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the seipin family.
Tissue Specificity
Expressed in motor neurons in the spinal cord and cortical neurons in the frontal lobe (at protein level). Highly expressed in brain, testis and adipose tissue.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Lipid droplet
- Localizes at endoplasmic reticulum-lipid droplets (ER-LD) contact sites.
Alternative names
Seipin, Bernardinelli-Seip congenital lipodystrophy type 2 protein, BSCL2