SACS (gene)
Encyclopedia
Sacsin also known as DnaJ homolog subfamily C member 29 (DNAJC29) is a protein
that in humans is encoded by the SACS gene
. Sacsin is a Hsp70
co-chaperone
.
at the C-terminus and a DnaJ
region upstream of the HEPN domain. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia
with spasticity
and peripheral neuropathy
.
regions of Quebec
or descendants of native settlers in this region. It is characterized by degeneration of the spinal cord and progressive damage of the peripheral nerves. The disorder is caused by a gene mutation on chromosome 13 (SACS) of the 22 chromosomes that determine characteristics that are not related to sex. This is an autosomal recessive disorder, meaning that both parents must be carriers of the gene in order to have a 25% chance of their child having the disorder at each pregnancy. Mutations of the gene is usually a deletion or replacement of a nucleotide in the SACS gene. The mutation of the SACS gene causes the production of an unstable, poorly functioning SACSIN protein. It is unclear as to how this mutation affects the central nervous system (CNS) and skeletal muscles presenting in the signs and symptoms of ARSACS.
ARSACS is usually diagnosed in early childhood, approximately 12-24 months of age when a child begins to take their first steps. It is a lack of coordination and balance during gait that is first noticed. Children with the disorder take frequent falls and appear to have an unsteady (Ataxic) gait. Some of the signs and symptoms include : Stiffness of the legs, appendicular and trunk ataxia
, hollow foot and hand deformities, ataxic dysarthria
, distal muscle wasting, horizontal gaze nystagmus
, and spasticity
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the SACS gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Sacsin is a Hsp70
Hsp70
The 70 kilodalton heat shock proteins are a family of ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms...
co-chaperone
Co-chaperone
Co-chaperones are proteins that assist chaperones in protein folding and other functions.-List of Co-chaperones:*Aha1*auxilin*BAG1*CAIR-1/Bag-3*CDC37/p50*Chp1*Cysteine string protein *Cyp40*Djp1*DnaJ*E3/E4-ubiquitin ligase*FKBP52*GAK*GroES...
.
Function
This gene consists of nine exons including a gigantic exon spanning more than 12.8k bp. It encodes the sacsin protein, which includes a UBQ region at the N-terminus, a HEPN domainHEPN domain
In molecular biology, the HEPN domain is a region of approximately 110 amino acids found in the C terminus of sacsin, a chaperonin implicated in an early-onset neurodegenerative disease in human, and in many bacterial and archeabacterial proteins...
at the C-terminus and a DnaJ
Chaperone DnaJ
In molecular biology, chaperone DnaJ, also known as Hsp40 , is a molecular chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans.-Function:...
region upstream of the HEPN domain. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia
Cerebellar ataxia
Cerebellar ataxia is a form of ataxia originating in the cerebellum.-References:...
with spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
and peripheral neuropathy
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
.
Clinical significance
Autosomal Recessive Spastic Ataxia of the Charlevoix Saguenay (ARSACS) is a hereditary progressive neurological disorder that primarily affects people from the Saguenay–Lac-Saint-Jean and CharlevoixCharlevoix
The Charlevoix region, located in Quebec, includes parts of the north shore of the Saint Lawrence River and the Laurentian Mountains region of the Canadian Shield...
regions of Quebec
Quebec
Quebec or is a province in east-central Canada. It is the only Canadian province with a predominantly French-speaking population and the only one whose sole official language is French at the provincial level....
or descendants of native settlers in this region. It is characterized by degeneration of the spinal cord and progressive damage of the peripheral nerves. The disorder is caused by a gene mutation on chromosome 13 (SACS) of the 22 chromosomes that determine characteristics that are not related to sex. This is an autosomal recessive disorder, meaning that both parents must be carriers of the gene in order to have a 25% chance of their child having the disorder at each pregnancy. Mutations of the gene is usually a deletion or replacement of a nucleotide in the SACS gene. The mutation of the SACS gene causes the production of an unstable, poorly functioning SACSIN protein. It is unclear as to how this mutation affects the central nervous system (CNS) and skeletal muscles presenting in the signs and symptoms of ARSACS.
ARSACS is usually diagnosed in early childhood, approximately 12-24 months of age when a child begins to take their first steps. It is a lack of coordination and balance during gait that is first noticed. Children with the disorder take frequent falls and appear to have an unsteady (Ataxic) gait. Some of the signs and symptoms include : Stiffness of the legs, appendicular and trunk ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, hollow foot and hand deformities, ataxic dysarthria
Dysarthria
Dysarthria is a motor speech disorder resulting from neurological injury of the motor component of the motor-speech system and is characterized by poor articulation of phonemes...
, distal muscle wasting, horizontal gaze nystagmus
Nystagmus
Nystagmus is a condition of involuntary eye movement, acquired in infancy or later in life, that may result in reduced or limited vision.There are two key forms of Nystagmus: pathological and physiological, with variations within each type. Nystagmus may be caused by congenital disorders,...
, and spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
.