Persius/hicric huggingface dataset:
SGCG
Gamma-sarcoglycan is a protein that in humans is encoded by the SGCG gene. The  to -sarcoglycans are expressed predominantly () or exclusively (,  and ) in striated muscle. A mutation in any of the sarcoglycan genes may lead to a secondary deficiency of the other sarcoglycan proteins, presumably due to destabilisation of the sarcoglycan complex.  The disease-causing mutations in the  to  genes cause disruptions within the dystrophin-associated protein (DAP) complex in the muscle cell membrane. The transmembrane components of the DAP complex link the cytoskeleton to the extracellular matrix in adult muscle fibres, and are essential for the preservation of the integrity of the muscle cell membrane.

# Function
Gamma-sarcoglycan is one of several sarcolemmal transmembrane glycoproteins that interact with dystrophin, probably to provide a link between the membrane associated cytoskeleton and the extracellular matrix.  Defects in the protein can lead to early onset autosomal recessive muscular dystrophy, in particular limb-girdle muscular dystrophy, type 2C (LGMD2C).

# Structure

## Gene
Human SGCG gene maps to chromosome 13 at q12, spans over 100 kb of DNA and includes 8 exons.

## Protein
Gamma-sarcoglycan is a type II transmembrane protein and consists of 291 amino acids. It has a 35 amino acid intracellular N-terminal region, a 25 amino acid single transmembrane domain, and a 231 amino acid extra-cellular C-terminus.

# Clinical significance
Sarcoglycanopathies are autosomal recessive limb girdle muscular dystrophies (LGMDs) caused by mutations in any of the four sarcoglycan genes:  (LGMD2D),  (LGMD2E),  (LGMD2C) and  (LGMD2F). Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a progressive muscle-wasting disorder that segregates with microsatellite markers at -sarcoglycan gene. Mutations in the -sarcoglycan gene were first described in the Maghreb countries of North Africa, where -sarcoglycanopathy has a higher than usual incidence. One common mutation, -521T, which causes a severe phenotype, occurs both in the Maghreb population and in other countries. A Cys283Tyr mutation has been identified in the Gypsy population causing a severe phenotype and a Leu193Ser mutation which causes a mild phenotype.

# Interactions
SGCG has been shown to interact with FLNC.
SGCZ
Sarcoglycan zeta also known as SGCZ is a protein which in humans is encoded by the SGCZ gene.

# Function
The zeta-sarcoglycan gene measures over 465 kb and localizes to 8p22. This protein is part of the sarcoglycan complex, a group of 6 proteins. The sarcoglycans are all N-glycosylated transmembrane proteins with a short intra-cellular domain, a single transmembrane region and a large extra-cellular domain containing a carboxyl-terminal cluster with several conserved cysteine residues. The sarcoglycan complex is part of the dystrophin-associated glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix.

# Clinical significance
Zeta-sarcoglycan is reduced in mouse models of muscular dystrophy and SGCZ is found as a component of the vascular smooth muscle sarcoglycan complex. Hence SGCZ  may be important in the pathogenesis of muscular dystrophy.
SGEF
SGEF (Src homology 3 domain-containing Guanine nucleotide Exchange Factor) is a 97 kDa protein involved in intracellular signalling networks. It functions as a guanine nucleotide exchange factor (GEF) for RhoG,  a small G protein of the Rho family.

# Discovery
SGEF was discovered during a screen for androgen-responsive genes in human prostate cancer cells. Subsequent northern blot analysis revealed expression of SGEF in tissues of the heart, brain, placenta, lung, liver, kidney, pancreas, prostate, testis, small intestine and colon. SGEF is also expressed in endothelial cells of the vasculature. Several widely used cell lines express this protein, these include A431, HeLa, HUT78, HEK-293, Jurkat, THP, PC12, RAJI, U937 and Meg-01.
SGEF was identified to contribute to the formation of atherosclerosis through promoting endothelial docking structures that resulted in retention of leukocytes at athero-prone sites of inflammation . Genetic variants in SGEF have been associated with coronary artery disease

# Structure and Function
SGEF is part of a large class of proteins (GEFs) that function to activate small G proteins. In their resting state G proteins are bound to guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting nucleotide exchange.
SGEF has the canonical GEF structure of tandem DH and PH domains, which elicit nucleotide exchange and, in addition, contains an N-terminal proline-rich motif and a C-terminal SH3 domain. Proline regions and SH3 domains often mediate recruitment and binding to adaptor proteins suggesting that SGEF is probably involved in the formation of heteromultimeric protein complexes.

# Regulation of SGEF activity
Data from several studies suggest that SGEF is regulated by its recruitment to transmembrane receptor-linked adaptor proteins via its SH3 domain. In one study, mutation of the SH3 domain disrupted SGEF-dependent functions in NIH-3T3 fibroblasts. In endothelial cells SGEF was recruited to the intracellular domain of the transmembrane adhesion molecule ICAM-1 upon leukocyte adhesion to the endothelium.
SGK3
Serine/threonine-protein kinase Sgk3 is an enzyme that in humans is encoded by the SGK3 gene.

# Function
This gene is a member of the serine/threonine protein kinase family and encodes a phosphoprotein with a PX (phox homology) domain. The protein phosphorylates several target proteins and has a role in neutral amino acid transport and activation of potassium and chloride channels. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
In melanocytic cells SGK3 gene expression may be regulated by MITF.

# Interactions
SGK3 has been shown to interact with GSK3B.
SIM1
Single-minded homolog 1 also known as class E basic helix-loop-helix protein 14 (bHLHe14) is a protein that in humans is encoded by the SIM1 gene.

# Function
SIM1 and SIM2 genes are homologs of Drosophila melanogaster single-minded (sim), so named because cells in the midline of the sim mutant embryo fail to properly develop and eventually die, and thus the paired longitudinal axon bundles that span the anterior-posterior axis of the embryo (analogous to the embryo's spinal cord) are collapsed into a "single" rudimentary axon bundle at the midline.  Sim is a basic helix-loop-helix-PAS domain transcription factor that regulates gene expression in the midline cells.  Since the sim gene plays an important role in Drosophila development and has peak levels of expression during the period of neurogenesis, it was proposed that the human SIM2 gene, which resides in a critical region of chromosome 21, is a candidate for involvement in certain dysmorphic features (particularly facial and skull characteristics), abnormalities of brain development, and/or mental retardation of Down syndrome.

# Clinical significance
Haploinsufficiency of SIM1 has been shown to cause severe early-onset obesity in a human girl with a de novo balanced translocation between chromosomes 1p22.1 and 6q16.2  and has been suggested to cause a Prader-Willi-like phenotype in other cases. Additionally, studies in mice have shown that haploinsufficieny of Sim1 causes obesity that is due to hyperphagia and do not respond properly to increased dietary fat. Overexpression of SIM1 protects against diet induced obesity and rescues the hyperphagia of agouti yellow mice, who have disrupted melanocortin signaling. The obesity and hyperphagia may be mediated by impaired melanocortin activation of PVN neurons  and oxytocin deficiency in these mice. It has been demonstrated that modulating Sim1 levels postnatally also leads to hyperphagia and obesity, suggesting a physiological role for Sim1 separate from its role in development.

# Interactions
SIM1 has been shown to interact with Aryl hydrocarbon receptor nuclear translocator.
SIX1
Homeobox protein SIX1 (Sineoculis homeobox homolog 1) is a protein that in humans is encoded by the SIX1 gene.

# Function
The vertebrate SIX genes are homologs of the Drosophila 'sine oculis' (so) gene, which is expressed primarily in the developing visual system of the fly. Members of the SIX gene family encode proteins that are characterized by a divergent DNA-binding homeodomain and an upstream SIX domain, which may be involved both in determining DNA-binding specificity and in mediating proteinprotein interactions. Genes in the SIX family have been shown to play roles in vertebrate and insect development or have been implicated in maintenance of the differentiated state of tissues.

# Interactions
SIX1 has been shown to interact with EYA1, DACH, GRO and MDFI.
SIX3
Homeobox protein SIX3 is a protein that in humans is encoded by the SIX3 gene.

# Function
The SIX homeobox 3 (SIX3) gene is crucial in embryonic development by providing necessary instructions for the formation of the forebrain and eye development. SIX3 is a transcription factor that binds to specific DNA sequences, controlling whether the gene is active or inactive. Activity of the SIX3 gene represses Wnt1 gene activity which ensures development of the forebrain and establishes the proper anterior posterior identity in the mammalian brain. By blocking Wnt1 activity, SIX3 is able to prevent abnormal expansion of the posterior portion of the brain into the anterior brain area.
During retinal development, SIX3 has been proven to hold a key responsibility in the activation of Pax6, the master regulator of eye development. Furthermore, SIX3 assumes its activity in the PLE (presumptive lens ectoderm), the region in which the lens is expected to develop. If its presence is removed from this region, the lens fails to thicken and construct itself to its proper morphological state. Also, SIX3 plays a strategic role in the activation of SOX2.
SIX3 has also been proven to play a role in repression of selected members of the Wnt family. In retinal development, SIX3 is responsible for the repression of Wnt8b. Also, in forebrain development, SIX3 is responsible for the repression of Wnt1 and activation of SHH, Sonic Hedgehog gene.

# Clinical significance
Mutations in SIX3 are the cause of a severe brain malformation, called holoprosencephaly type 2 (HPE2). In HPE2, the brain fails to separate into two hemispheres during early embryonic development, leading to eye and brain malformations, which result in serious facial abnormalities.
A mutant zebrafish knockout model has been developed, in which the anterior part of the head was missing due to the atypical increase of Wnt1 activity. When injected with SIX3, these zebrafish embryos were able to successfully develop a normal forebrain. When SIX3 was turned off in mice, resulting in a lack of retina formation due to excessive expression of Wnt8b in the region where the forebrain normally develops. Both of these studies demonstrate the importance of SIX3 activity in brain and eye development.

# Interactions
SIX3 has been shown to interact with TLE1 and Neuron-derived orphan receptor 1.
SLBP
Histone RNA hairpin-binding protein or stem-loop binding protein (SLBP) is a protein that in humans is encoded by the SLBP gene.

# Species distribution
SLBP has been cloned from humans,  C. elegans, D. melanogaster, X. laevis, and sea urchins.  The full length human protein has 270 amino acids (31 kDa) with a centrally located RNA binding domain (RBD).  The 75 amino acid RBD is well conserved across species, however the remainder of SLBP is highly divergent in most organisms and not homologous to any other protein in the eukaryotic genomes.

# Function
This gene encodes a protein that binds to the histone 3' UTR stem-loop structure in replication-dependent histone mRNAs. Histone mRNAs do not contain introns or polyadenylation signals, and are processed by a single endonucleolytic cleavage event downstream of the stem-loop. The stem-loop structure is essential for efficient processing of the histone pre-mRNA but this structure also controls the transport, translation and stability of histone mRNAs. SLBP expression is regulated during S-phase of the cell cycle, increasing more than 10-fold during the latter part of G1.
All SLBP proteins are capable of forming a highly stable complex with histone stem-loop RNA. Complex formation with the histone mRNA stem-loop is achieved by a novel three-helix bundle fold.  SLBP proteins also recognize the tetraloop structure of the histone hairpin, the base of the stem, and the 5' flanking region. The crystal structure of human SLBP in complex with the stem-loop RNA as well as the exonuclease Eri1 reveals that the Arg181 residue of SLBP specifically interacts with the second guanine base in the RNA stem. The rest of the protein is intrinsically disordered in fruit-flies as well as in humans.  A unique feature of the SLBP RBD is that it is phosphorylated in its RNA binding domain at the Thr171 residue. The SLBP RBD also undergoes proline isomerization about this sequence and is a substrate for the prolyl isomerase Pin1.  The N-terminal domain of human SLBP is required for translation activation of histone mRNAs via its interaction with SLIP1.  SLBP also interacts with the CBP80 associated protein CTIF to facilitate rapid degradation of histone mRNAs.  SLBP is a phosphoprotein and besides T171, it is also phosphorylated at Ser7, Ser20, Ser23, Thr60, Thr61 in mammalian cells.  The phosphorylation at Thr60 is mediated by CK2 and Thr61 is by Cyclin A/Cdk1.
SLUD
SLUD (Salivation, Lacrimation, Urination, Defecation ) is a syndrome of pathological effects indicative of massive discharge of the parasympathetic nervous system.  Unlikely to occur naturally, SLUD is usually encountered only in cases of drug overdose or exposure to nerve gases.  Nerve gases irreversibly inhibit the enzyme  acetylcholinesterase; this results in a chronically high level of acetylcholine at cholinergic synapses throughout the body, thus chronically stimulating acetylcholine receptors throughout the body.  The symptoms of SLUD are due to chronic stimulation of muscarinic acetylcholine receptors, in organs and muscles innervated by the parasympathetic nervous system:
- Salivation:     stimulation of the salivary glands
- Lacrimation:    stimulation of the lacrimal glands
- Urination:      relaxation of the internal urinary sphincter, and contraction of the detrusor muscles
- Defecation:     relaxation of the internal anal sphincter
- Emesis:         stimulation of brainstem emesis center
One common cause of SLUD is exposure to organophosphorus insecticides, including parathion, malathion, and diazinon. These agents phosphorylate acetylcholinesterase, thereby raising the acetylcholine levels and causing SLUD.
SLX4
SLX4 (also known as BTBD12 and FANCP) is a protein involved in DNA repair, where it has important roles in the final steps of homologous recombination. Mutations in the gene are associated with the disease Fanconi anemia.
The version of SLX4 present in humans and other mammals acts as a sort of scaffold upon which other proteins form several different multiprotein complexes.  The SLX1-SLX4 complex acts as a Holliday junction resolvase.  As such, the complex cleaves the links between two homologous chromosomes that form during homologous recombination.  This allows the two linked chromosomes to resolve into two unconnected double-strand DNA molecules.  SLX4 also associates with RAD1, RAD10 and SAW1 in the single-strand annealing pathway of homologous recombination. The DNA repair function of SLX4 is involved in sensitivity to proton beam radiation.

# Model organisms
Model organisms have been prominent in the study of SLX4 function. It was identified in 2001 during a screen for lethal mutations in yeast cells lacking a functional copy of the Sgs1 protein.  Based on that, SLX4 was grouped with several other proteins produced by SLX (synthetic lethal of unknown function) genes.
A conditional knockout mouse line, called Slx4tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program, a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice and ten significant abnormalities were observed. A viability at weaning study found less homozygous mutant animals were present than predicted by Mendelian ratio. Homozygous mutant animals of both sexes were sub-fertile and homozygous females had a reduced body weight, body length, heart weight, platelet count and lean mass. Homozygotes of both sex had abnormal eye sizes, narrow eye openings, skeletal defects (including scoliosis and fusion of vertebrae), and displayed an increase in DNA instability as shown by a micronucleus test. This and further analysis revealed the mouse phenotype to model the human genetic illness, Fanconi anemia. The association was confirmed when patients with the disease were found to have mutations in their SLX4 gene.
SMC3
Structural maintenance of chromosomes protein 3 (SMC-3) is a nuclear protein that in humans is encoded by the SMC3 gene. A post-translated modified form that is excreted is known as basement membrane-associated chondroitin proteoglycan (bamacan).

# Function
This gene belongs to the SMC3 subfamily of SMC proteins. The encoded protein occurs in certain cell types as either an intracellular, nuclear protein or a secreted protein. The nuclear form, known as structural maintenance of chromosomes 3, is a component of the multimeric cohesin complex that holds together sister chromatids during mitosis, enabling proper chromosome segregation. Post-translational modification of the encoded protein by the addition of chondroitin sulfate chains gives rise to the secreted proteoglycan bamacan, an abundant basement membrane protein.
SMC3 protein appears to participate with other cohesins REC8, STAG3 and SMC1 in sister-chromatid cohesion throughout the whole meiotic process in human oocytes.

# Model organisms
Model organisms have been used in the study of SMC3 function. A conditional knockout mouse line, called Smc3tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on mutant mice and six significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and thus none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice. Females had a higher than normal incidence of pre-wean death in their offspring, and also had a decreased body weight. Males heterozygotes displayed a shortened, upturned snout.

# Cornelia de Lange syndrome
Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that presents with variable clinical abnormalities including dysmorphic features, severe growth retardation, global developmental delay, and intellectual disability.  SMC3 is one of five genes that have been implicated in CdLS.  In one case report, a novel SMC3 gene duplication was detected in a child with failure to thrive, hypotonia and facial dysmorphic features of CdLS.  The same duplication was also observed in the mother, who had milder dysmorphic facies.

# Interactions
SMC3 (gene) has been shown to interact with:
- KIFAP3,
- MXD1,
- MXI1,
- REC8,  and
- SMC1A.
SMC5
Structural maintenance of chromosomes protein 5 is a protein encoded by the SMC5 gene in human.
It is involved in the Alternative lengthening of telomeres cancer mechanism.

# Role in recombination and meiosis
Smc5 and Smc6 proteins form a heterodimeric ring-like structure and together with other non-SMC elements form the SMC-5/6 complex.  In the worm Caenorhabditis elegans this complex interacts with the HIM-6(BLM) helicase to promote meiotic recombination intermediate processing and chromosome maturation.  The SMC-5/6 complex in mouse oocytes is essential for the formation of segregation competent bivalents during meiosis.  In humans, a chromosome breakage syndrome characterized by severe lung disease in early childhood is associated with a mutation in a component of the SMC-5/6 complex.  Patients cells display chromosome rearrangements, micronuclei, sensitivity to DNA damage and defective homologous recombination.
SMC6
Structural maintenance of chromosomes protein 6 is a protein that in humans is encoded by the SMC6 gene.
It is involved in the Alternative lengthening of telomeres cancer mechanism.

# Role in recombination and meiosis
Smc6 and Smc5 proteins form a heterodimeric ring-like structure and together with other non-SMC elements form the SMC-5/6 complex.  In the worm Caenorhabditis elegans this complex interacts with the HIM-6(BLM) helicase to promote meiotic recombination intermediate processing and chromosome maturation.  The SMC-5/6 complex in mouse oocytes is essential for the formation of segregation competent bivalents during meiosis.  In the yeast Saccharomyces cerevisiae, SMC6 is necessary for resistance to DNA damage as well as for damage-induced interchromosomal and sister chromatid recombination.  In humans, a chromosome breakage syndrome characterized by severe lung disease in early childhood is associated with a mutation in a component of the SMC-5/6 complex.  Patients cells display chromosome rearrangements, micronuclei, sensitivity to DNA damage and defective homologous recombination.
SMG1
Serine/threonine-protein kinase SMG1 is an enzyme that in humans is encoded by the SMG1 gene. SMG1 belongs to the phosphatidylinositol 3-kinase-related kinase protein family.

# Function
This gene encodes a protein involved in nonsense-mediated mRNA decay (NMD) as part of the mRNA surveillance complex. The protein has kinase activity and is thought to function in NMD by phosphorylating the regulator of nonsense transcripts 1 protein. Alternative spliced transcript variants have been described, but their full-length natures have not been determined.

# Interactions
SMG1 (gene) has been shown to interact with PRKCI and UPF1.
SMN1
Survival of motor neuron 1 (SMN1), also known as component of gems 1 or GEMIN1, is a gene that encodes the SMN protein in humans.

# Gene
SMN1 is the telomeric copy of the gene encoding the SMN protein; the centromeric copy is termed SMN2. SMN1 and SMN2 are part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. SMN1 and SMN2 are nearly identical and encode the same protein. The critical sequence difference between the two is a single nucleotide in exon 7 which is thought to be an exon splice enhancer. It is thought that gene conversion events may involve the two genes, leading to varying copy numbers of each gene.

# Clinical significance
Mutations in SMN1 are associated with spinal muscular atrophy. Mutations in SMN2 alone do not lead to disease, although mutations in both SMN1 and SMN2 result in embryonic death.