S100B

Summary

S100B (S100 calcium binding protein B, HGNC:10500) is a protein-coding gene on chromosome 21q22.3, encoding Protein S100-B (P04271). Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain.

The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21; however, this gene is located at 21q22.3. This protein may function in Neurite extension, proliferation of melanoma cells, stimulation of Ca2+ fluxes, inhibition of PKC-mediated phosphorylation, astrocytosis and axonal proliferation, and inhibition of microtubule assembly. Chromosomal rearrangements and altered expression of this gene have been implicated in several neurological, neoplastic, and other types of diseases, including Alzheimer’s disease, Down’s syndrome, epilepsy, amyotrophic lateral sclerosis, melanoma, and type I diabetes.

Source: NCBI Gene 6285 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 12 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006272

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10500
Approved symbol	S100B
Name	S100 calcium binding protein B
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	S100beta
Ensembl gene	ENSG00000160307
Ensembl biotype	protein_coding
OMIM	176990
Entrez	6285

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000291700, ENST00000367071, ENST00000397648, ENST00000877391, ENST00000877392, ENST00000877393, ENST00000877394, ENST00000877395, ENST00000877396, ENST00000928840, ENST00000963271, ENST00000963272, ENST00000963273

RefSeq mRNA: 1 — MANE Select: NM_006272 NM_006272

CCDS: CCDS13736

Canonical transcript exons

ENST00000291700 — 3 exons

Exon	Start	End
ENSE00001051347	46602278	46602416
ENSE00003554900	46598604	46599503
ENSE00003846634	46605013	46605082

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 99.93.

FANTOM5 (CAGE): breadth broad, TPM avg 48.4465 / max 3522.6288, expressed in 445 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190942	48.3938	445
190941	0.0527	30

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.93	gold quality
inferior vagus X ganglion	UBERON:0005363	99.85	gold quality
olfactory bulb	UBERON:0002264	99.84	gold quality
subthalamic nucleus	UBERON:0001906	99.77	gold quality
trigeminal ganglion	UBERON:0001675	99.75	gold quality
medial globus pallidus	UBERON:0002477	99.74	gold quality
spinal cord	UBERON:0002240	99.73	gold quality
globus pallidus	UBERON:0001875	99.72	gold quality
medulla oblongata	UBERON:0001896	99.71	gold quality
superior vestibular nucleus	UBERON:0007227	99.69	gold quality
pons	UBERON:0000988	99.67	gold quality
midbrain	UBERON:0001891	99.67	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.67	gold quality
substantia nigra	UBERON:0002038	99.67	gold quality
cranial nerve II	UBERON:0000941	99.62	gold quality
ventral tegmental area	UBERON:0002691	99.61	gold quality
tibial nerve	UBERON:0001323	99.60	gold quality
lateral globus pallidus	UBERON:0002476	99.60	gold quality
substantia nigra pars compacta	UBERON:0001965	99.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.48	gold quality
hypothalamus	UBERON:0001898	99.44	gold quality
nucleus accumbens	UBERON:0001882	99.41	gold quality
inferior olivary complex	UBERON:0002127	99.35	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.33	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.33	gold quality
right frontal lobe	UBERON:0002810	99.29	gold quality
putamen	UBERON:0001874	99.25	gold quality
amygdala	UBERON:0001876	99.24	gold quality
cerebellar hemisphere	UBERON:0002245	99.24	gold quality
cerebellar cortex	UBERON:0002129	99.15	gold quality

Single-cell (SCXA)

Detected in 34 experiment(s), a significant marker in 33.

Experiment	Marker?	Max mean expression
E-MTAB-8207	yes	8967.35
E-ENAD-20	yes	7818.38
E-GEOD-124263	yes	4548.26
E-MTAB-8221	yes	4088.48
E-MTAB-10042	yes	3611.13
E-MTAB-8410	yes	3473.54
E-HCAD-25	yes	3348.33
E-MTAB-10485	yes	2920.44
E-GEOD-84465	yes	2672.14
E-HCAD-5	yes	2669.80
E-MTAB-7407	yes	2490.24
E-HCAD-11	yes	2150.01
E-CURD-79	yes	2052.39
E-GEOD-81383	yes	1831.20
E-CURD-126	yes	1669.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, GLI3, HOXC11, HOXC6, NCOA1, TEAD4, TFAP2A, TP53

miRNA regulators (miRDB)

26 targeting S100B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-12127	97.93	66.67	793
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-1287-5P	96.80	65.30	743

Literature-anchored findings (GeneRIF, showing 40)

• This study provides evidence that circulating S100beta protein is increased in IUGR fetuses and correlates with cerebral hemodynamics, suggesting that it may represent an index of cerebral cell damage in the perinatal period. (PMID:11809917)
• role of N-terminal helix I for dimerization and stability (PMID:11888280)
• A study of S100B identifying key regions required for the interaction with S100B-binding epitope TRTK-12 shows that the S100B linker region contributes about 50% to binding while the C-terminus contributes the remaining 50% of the binding energy. (PMID:11969402)
• preoperative S100B concentrations correlate inversely with the size of the ascending aorta in hypoplastic left heart syndrome and may serve as a marker for preexisting brain injury and mortality (PMID:12351263)
• the major cytoplasmic S100B target protein in different glial cell lines in the presence of Zn(2+) and Ca(2+) is IQGAP1 (PMID:12377780)
• A new target is revealed by the solution structure of a peptide fragment. (PMID:12480931)
• Serum S100B is increased in almost half of children after mild, moderate, and severe inflicted and noninflicted closed head injury; the increase is transient, lasting less than 12 h after injury, except in children with severe injury. (PMID:12490005)
• Cerebrospinal fluid S100B correlates with brain atrophy in Alzheimer’s disease, suggesting that S100B is of pathological relevance for degeneration of the central nervous system in Alzheimer’s disease. (PMID:12505619)
• presence in human milk - may contribute to biochemical communication between mother and child (PMID:12527118)
• Elevated serum S100B level was associated with metastatic malignant melanoma (PMID:12569284)
• S 100 B may be a reliable marker of brain damage in TBI without multiple trauma 24 h after trauma and thereafter (PMID:12630517)
• increased levels have been detected in brain trauma and ischemia, and in neurodegenerative, inflammatory and psychiatric diseases, probably due to release from damaged astrocytes (PMID:12645009)
• Results in high-risk pregnancies demonstrated that S100B concentration increased in amniotic fluid and in cord blood of fetuses with brain damage [review] (PMID:12927678)
• Review summarizes current knowledge about S-100B serum measurements in severe head injury and concludes that S-100B belongs to a new generation of molecular serum markers of brain damage. (PMID:14530578)
• S100 beta showed a significant decrease in CSF over the disease course (P=0.024). (PMID:14642437)
• positively correlated with Phe blood level in phenylketonuria patients; blood estimation could be a useful peripheral marker of CNS lesions in patients with demyelinated disease such as PKU (PMID:14675567)
• Protein S-100b might be a promising serum marker with prognostic significance in the event of spinal cord compression resulting from epidural empyema. (PMID:14699277)
• results indicate that human S100B expressed in E Coli interacts with the tubulin homologue FtsZ in vivo, modulating its activity in bacterial cell division. (PMID:14967825)
• S100B in schizophrenic patients either promotes apoptotic mechanisms by itself or is released from astrocytes as part of an attempt to repair a degenerative or destructive process (PMID:14997170)
• when p53 protein levels increase, it contributes to its own demise by up-regulating the transcription of S100B protein as part of a negative feedback loop (PMID:15178678)
• results support the idea that elevated levels of S100B in the brain are associated with increased vulnerability to neurological injury (PMID:15236402)
• S100B and IL-1beta in the cerebrospinal fluid may have a role in the progression of traumatic brain injury (PMID:15257081)
• S100B overexpression in young (70 days) and aged (200 days) adult transgenic mice leads to alterations in cytoskeletal markers with aging. (PMID:15306236)
• Our results suggest that S100B could be a susceptible gene for schizophrenia and provide indirect evidence for the GGF/SD hypothesis. (PMID:15670788)
• The present study offers data consistent with the putative neurotrophic role of S100B and suggests the usefulness of saliva in the clinical monitoring of S100B levels. (PMID:15708543)
• S100B regulates the oligomerization of p53 tumor suppressor by binding to its tetramerization domain. (PMID:15781852)
• The higher levels of S100B in Down Syndrome patients may reflect a general and persistent increase in the extracellular space and may be associated with neurodegenerative lesions observed in these patients. (PMID:15820773)
• Study indicates that the serum concentration of S100B in patients with neural tube defects is similar to that of normal individuals. (PMID:16143320)
• determination of urinary S-100B concentrations might be helpful in term infants with severe asphyxia, while high urinary S-100B concentrations in preterm infants are to be attributed to immaturity (PMID:16340181)
• X-ray diffraction studies on human Ca2+-binding protein S100B (PMID:16511125)
• IP-10 mRNA is stabilized by RNA-binding proteins in monocytes treated with S100b (PMID:16931519)
• Increased plasma S100B level is found following acute spontaneous intracerebral hemorrhage, in association with a worse early and late evolution, and closely related to initial hematoma volume. (PMID:17008613)
• Phosphorylation of specific serine and/or threonine residues reduces the affinity of the S100B-p53 interaction. (PMID:17010455)
• Serum S100beta levels may serve as a potentially useful early marker of postcraniotomy brain damage in patients undergoing elective meningioma resection. (PMID:17020600)
• Amniotic fluid S100B protein concentration of the pre-eclampsia & normotensive IUGR cases was significantly higher than that of the control. Amnion could be a source responsible for the increased concentration of S100B in amniotic fluid. (PMID:17023485)
• finding of increased levels of S100B in patients with schizophrenia without an indication for significant glial (GFAP, MBP) or neuronal (NSE) damage may be interpreted as indirect evidence for increased active secretion of S100B during acute psychosis (PMID:17043297)
• S100B protein levels are affected differently in alcohol-dependent individuals with either mild or high alcohol consumption during the period of up to one year before assessment. (PMID:17091777)
• S100B is localized in many neural cell-types and is less astrocyte-specific than GFAP. (PMID:17199889)
• S-100B and MIA concentrations were significantly higher in patients with uveal melanoma metastases (PMID:17264538)
• Review examines S100B’s potential role as a neurologic screening tool, or biomarker of CNS injury, analogous to the role of CRP as a marker of systemic inflammation. (PMID:17348038)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	s100b	ENSDARG00000057598
mus_musculus	S100b	ENSMUSG00000033208
rattus_norvegicus	S100b	ENSRNOG00000001295

Paralogs (21): CRNN (ENSG00000143536), S100A8 (ENSG00000143546), S100A7 (ENSG00000143556), S100A1 (ENSG00000160678), S100A11 (ENSG00000163191), S100A9 (ENSG00000163220), S100A12 (ENSG00000163221), S100P (ENSG00000163993), S100G (ENSG00000169906), S100Z (ENSG00000171643), S100A7A (ENSG00000184330), S100A3 (ENSG00000188015), S100A16 (ENSG00000188643), SNTN (ENSG00000188817), S100A13 (ENSG00000189171), S100A14 (ENSG00000189334), S100A4 (ENSG00000196154), S100A5 (ENSG00000196420), S100A2 (ENSG00000196754), S100A10 (ENSG00000197747), S100A6 (ENSG00000197956)

Protein

Protein identifiers

Protein S100-B — P04271 (reviewed: P04271)

Alternative names: S-100 protein beta chain, S-100 protein subunit beta, S100 calcium-binding protein B

All UniProt accessions (3): P04271, A0A0S2Z4C5, A8MRB1

UniProt curated annotations — full annotation on UniProt →

Function. Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain. Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Acts as a neurotrophic factor that promotes astrocytosis and axonal proliferation. Involved in innervation of thermogenic adipose tissue by acting as an adipocyte-derived neurotrophic factor that promotes sympathetic innervation of adipose tissue. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization. May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity.

Subunit / interactions. Dimer of either two alpha chains, or two beta chains, or one alpha and one beta chain. The S100B dimer binds two molecules of STK38. Interacts with CACYBP in a calcium-dependent manner. Interacts with ATAD3A; this interaction probably occurs in the cytosol prior to ATAD3A mitochondrial targeting. Interacts with S100A6. The S100B dimer interacts with two molecules of CAPZA1. Interacts with AGER. Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity. Interacts with TPPP; this interaction inhibits TPPP dimerization. Interacts with isoform CLSTN3beta of CLSTN3; interaction promotes secretion.

Subcellular location. Cytoplasm. Nucleus. Secreted.

Tissue specificity. Although predominant among the water-soluble brain proteins, S100 is also found in a variety of other tissues.

Similarity. Belongs to the S-100 family.

RefSeq proteins (1): NP_006263* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001751	S100/CaBP7/8-like_CS	Conserved_site
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR013787	S100_Ca-bd_sub	Domain
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR028481	S100-B	Family

Pfam: PF00036, PF01023

UniProt features (30 total): binding site 14, helix 5, strand 3, modified residue 2, domain 2, turn 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
5D7F	X-RAY DIFFRACTION	1.3
3CZT	X-RAY DIFFRACTION	1.4
3D0Y	X-RAY DIFFRACTION	1.5
3D10	X-RAY DIFFRACTION	1.65
2H61	X-RAY DIFFRACTION	1.9
3HCM	X-RAY DIFFRACTION	2
5CSI	X-RAY DIFFRACTION	2.13
5CSF	X-RAY DIFFRACTION	2.4
4XYN	X-RAY DIFFRACTION	2.55
5CSJ	X-RAY DIFFRACTION	2.7
5CSN	X-RAY DIFFRACTION	2.95
1MQ1	SOLUTION NMR
1UWO	SOLUTION NMR
2M49	SOLUTION NMR
2PRU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04271-F1	91.08	0.72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (14): 32; 62; 64; 66; 68; 73; 86; 91; 16; 19; 22; 24 …

Post-translational modifications (2): 2, 2

Function

Pathways and Gene Ontology

Reactome pathways

30 pathways

ID	Pathway
R-HSA-1251985	Nuclear signaling by ERBB4
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-879415	Advanced glycosylation endproduct receptor signaling
R-HSA-933542	TRAF6 mediated NF-kB activation
R-HSA-1236394	Signaling by ERBB4
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-446652	Interleukin-1 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9020702	Interleukin-1 signaling
R-HSA-937061	TRIF (TICAM1)-mediated TLR4 signaling
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975155	MyD88 dependent cascade initiated on endosome
R-HSA-975871	MyD88 cascade initiated on plasma membrane

MSigDB gene sets: 249 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, GOBP_MEMORY, AGGAAGC_MIR5163P, GOBP_RESPONSE_TO_ETHANOL, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_SKELETAL_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION

GO Biological Process (24): cell adhesion (GO:0007155), axonogenesis (GO:0007409), central nervous system development (GO:0007417), learning or memory (GO:0007611), memory (GO:0007613), positive regulation of cell population proliferation (GO:0008284), regulation of cell shape (GO:0008360), positive regulation of myelination (GO:0031643), positive regulation of apoptotic process (GO:0043065), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), response to ethanol (GO:0045471), positive regulation of neuron differentiation (GO:0045666), regulation of neuronal synaptic plasticity (GO:0048168), astrocyte differentiation (GO:0048708), response to glucocorticoid (GO:0051384), response to methylmercury (GO:0051597), long-term synaptic potentiation (GO:0060291), cellular response to hypoxia (GO:0071456), response to anesthetic (GO:0072347), sympathetic neuron projection extension (GO:0097490), adaptive thermogenesis (GO:1990845), negative regulation of skeletal muscle cell differentiation (GO:2001015), positive regulation of synaptic transmission (GO:0050806), neuron projection extension (GO:1990138)

GO Molecular Function (11): calcium ion binding (GO:0005509), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), S100 protein binding (GO:0044548), tau protein binding (GO:0048156), calcium-dependent protein binding (GO:0048306), RAGE receptor binding (GO:0050786), signaling receptor binding (GO:0005102), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): ruffle (GO:0001726), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), ciliary basal body (GO:0036064), neuronal cell body (GO:0043025), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Toll-like Receptor Cascades	6
Innate Immune System	2
Immune System	2
Toll Like Receptor 4 (TLR4) Cascade	2
Toll Like Receptor 2 (TLR2) Cascade	2
Signaling by ERBB4	1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
Toll Like Receptor 3 (TLR3) Cascade	1
Interleukin-1 signaling	1
TRIF (TICAM1)-mediated TLR4 signaling	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1
MyD88 cascade initiated on plasma membrane	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
Signaling by Receptor Tyrosine Kinases	1
Toll Like Receptor TLR1:TLR2 Cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein binding	4
positive regulation of cellular process	2
regulation of synaptic plasticity	2
response to chemical	2
plasma membrane bounded cell projection	2
cytoplasm	2
cellular process	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
nervous system development	1
system development	1
behavior	1
cognition	1
learning or memory	1
cell population proliferation	1
regulation of cell population proliferation	1
regulation of cell morphogenesis	1
regulation of biological quality	1
regulation of myelination	1
positive regulation of nervous system process	1
myelination	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
response to alcohol	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
central nervous system development	1
glial cell differentiation	1
response to corticosteroid	1
positive regulation of synaptic transmission	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1

Protein interactions and networks

STRING

2710 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S100B	AGER	Q15109	995
S100B	TP53	P04637	990
S100B	SDF4	Q9BRK5	937
S100B	GFAP	P14136	902
S100B	ENO2	P09104	881
S100B	TLR4	O00206	844
S100B	ALCAM	Q13740	844
S100B	FGF2	P09038	822
S100B	S100A1	P23297	814
S100B	MAPT	P10636	802
S100B	BDNF	P23560	786
S100B	RBFOX3	A6NFN3	765
S100B	RPS6KA1	Q15418	758
S100B	CALB1	P05937	756
S100B	MIA	Q16674	746

IntAct

233 interactions, top by confidence:

A	B	Type	Score
S100A1	S100B	psi-mi:“MI:0915”(physical association)	0.970
S100B	S100A1	psi-mi:“MI:0915”(physical association)	0.970
S100A1	S100B	psi-mi:“MI:2364”(proximity)	0.970
S100B	S100B	psi-mi:“MI:0915”(physical association)	0.960
S100B	S100B	psi-mi:“MI:0407”(direct interaction)	0.960

BioGRID (232): S100B (Two-hybrid), S100B (Two-hybrid), S100B (Two-hybrid), S100B (Two-hybrid), S100P (Two-hybrid), SPG21 (Two-hybrid), S100B (Two-hybrid), S100B (Two-hybrid), S100B (Two-hybrid), S100B (Two-hybrid), S100B (Two-hybrid), S100B (Two-hybrid), DNAJC30 (Two-hybrid), ADTRP (Two-hybrid), IMP4 (Two-hybrid)

ESM2 similar proteins: O77691, O77791, P02638, P02639, P04271, P04354, P04467, P04631, P05937, P05942, P05964, P06702, P06703, P07091, P07171, P10462, P12658, P14069, P23297, P24479, P25815, P26447, P27004, P28318, P29034, P30801, P31151, P35466, P35467, P50114, P56565, P79105, P79880, P80310, P80511, P97352, Q0VCM0, Q14ST5, Q28050, Q2EN75

Diamond homologs: A7K6Y9, O77691, O77791, P02632, P02633, P02634, P02638, P02639, P04271, P04631, P05942, P05964, P06702, P06703, P07091, P10462, P14069, P20930, P23297, P24480, P25815, P26447, P27003, P28318, P28783, P29034, P29377, P30801, P33763, P33764, P35466, P35467, P50114, P50116, P50117, P56565, P62818, P62819, P63083, P63084

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HOXC6	“up-regulates quantity by expression”	S100B	“transcriptional regulation”
HOXC11	“up-regulates quantity by expression”	S100B	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	6	20.8×	2e-04
Toll Like Receptor TLR6:TLR2 Cascade	5	20.0×	5e-04
Toll Like Receptor 2 (TLR2) Cascade	5	19.7×	5e-04
Toll Like Receptor TLR1:TLR2 Cascade	5	19.1×	5e-04
Toll Like Receptor 4 (TLR4) Cascade	5	14.9×	1e-03
Toll-like Receptor Cascades	5	14.1×	2e-03
Signaling by Interleukins	6	8.8×	3e-03
Class I MHC mediated antigen processing & presentation	5	8.0×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
axonogenesis	5	14.6×	6e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

12 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

495 predictions. Top by Δscore:

Variant	Effect	Δscore
21:46604979:T:TA	donor_gain	1.0000
21:46605033:T:TA	donor_gain	1.0000
21:46602426:C:CT	acceptor_gain	0.9900
21:46605007:TCTCA:T	donor_loss	0.9900
21:46605009:TCA:T	donor_loss	0.9900
21:46605010:CACCT:C	donor_loss	0.9900
21:46605011:ACC:A	donor_loss	0.9900
21:46605012:C:CG	donor_loss	0.9900
21:46605012:CCT:C	donor_gain	0.9900
21:46605017:T:TA	donor_gain	0.9900
21:46599501:TTCC:T	acceptor_loss	0.9800
21:46599502:TCCTA:T	acceptor_loss	0.9800
21:46599503:CCTA:C	acceptor_loss	0.9800
21:46599505:T:G	acceptor_loss	0.9800
21:46602273:CTCA:C	donor_loss	0.9800
21:46602274:TCA:T	donor_loss	0.9800
21:46602275:CA:C	donor_loss	0.9800
21:46602277:CCT:C	donor_gain	0.9800
21:46599506:A:C	acceptor_loss	0.9700
21:46599500:TTTC:T	acceptor_gain	0.9600
21:46599504:C:CC	acceptor_gain	0.9600
21:46604988:T:TA	donor_gain	0.9600
21:46605027:ACC:A	donor_gain	0.9600
21:46605028:CCC:C	donor_gain	0.9600
21:46602270:AGACT:A	donor_loss	0.9500
21:46602271:GACTC:G	donor_loss	0.9500
21:46602272:ACTC:A	donor_loss	0.9500
21:46602358:C:CT	acceptor_gain	0.9500
21:46604980:C:A	donor_gain	0.9500
21:46602413:CATC:C	acceptor_gain	0.9200

AlphaMissense

627 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:46602371:G:C	F15L	0.992
21:46602371:G:T	F15L	0.992
21:46602373:A:G	F15L	0.992
21:46599420:G:C	F74L	0.981
21:46599420:G:T	F74L	0.981
21:46599422:A:G	F74L	0.981
21:46602309:A:G	L36P	0.973
21:46599429:G:C	F71L	0.972
21:46599429:G:T	F71L	0.972
21:46599431:A:G	F71L	0.972
21:46602318:A:G	L33P	0.966
21:46599400:A:T	V81D	0.961
21:46599409:A:T	V78D	0.961
21:46602360:G:A	S19F	0.959
21:46602333:A:G	L28P	0.958
21:46599421:A:G	F74S	0.957
21:46599406:G:T	A79D	0.955
21:46602372:A:G	F15S	0.955
21:46602333:A:T	L28Q	0.951
21:46599430:A:G	F71S	0.950
21:46599437:A:G	C69R	0.949
21:46599458:C:G	D62H	0.947
21:46599472:A:T	V57D	0.946
21:46602384:A:G	L11P	0.946
21:46602314:C:A	K34N	0.943
21:46602314:C:G	K34N	0.943
21:46599407:C:G	A79P	0.941
21:46602373:A:T	F15I	0.939
21:46602309:A:T	L36H	0.935
21:46602361:A:G	S19P	0.935

dbSNP variants (sampled 300 via entrez): RS1000022265 (21:46598352 C>A,T), RS1000253369 (21:46604046 A>G), RS1000377048 (21:46598498 C>T), RS1001889092 (21:46603393 G>A,C,T), RS1001919091 (21:46606985 T>C), RS1002417177 (21:46603115 G>T), RS1003068297 (21:46606089 C>T), RS1003090069 (21:46600175 G>A,C,T), RS1003558345 (21:46602130 C>A,G,T), RS1003924176 (21:46604619 A>G), RS1004220600 (21:46600482 C>T), RS1004313854 (21:46604359 G>A), RS1004839845 (21:46602447 C>T), RS1005109170 (21:46602175 G>A), RS1005173684 (21:46605080 G>A)

Disease associations

OMIM: gene MIM:176990 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001389_2	Lymphocyte count	9.000000e-06
GCST004490_2	Cerebrospinal fluid t-tau:AB1-42 ratio	3.000000e-08
GCST004490_3	Cerebrospinal fluid t-tau:AB1-42 ratio	3.000000e-08
GCST011739_13	Cutaneous leishmaniasis	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4300 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 27,049 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL55	PENTAMIDINE	4	27,049

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

10 potent at pChembl≥5 of 17 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.00	Kd	1000	nM	PENTAMIDINE
5.70	IC50	2000	nM	CHEMBL1478187
5.70	Kd	2000	nM	CHEMBL185802
5.44	Ki	3600	nM	CHEMBL2335383
5.35	Kd	4500	nM	CHEMBL434915
5.35	Kd	4500	nM	CHEMBL364410
5.30	Ki	5000	nM	CHEMBL2094307
5.17	IC50	6800	nM	CHEMBL2335383
5.09	Kd	8100	nM	CHEMBL365434
5.08	IC50	8400	nM	CHEMBL2094307

PubChem BioAssay actives

11 with measured affinity, of 30 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Pentamidine	238034: Binding to holo-S100B protein	kd	1.0000	uM
2,4-di(piperidin-1-yl)aniline	734556: Inhibition of human S100B/human TAMRA-p53(367-388) interaction by fluorescence polarization assay	ki	1.0000	uM
1-(diaminomethylidene)-2-(2,3-dichlorophenyl)guanidine	238034: Binding to holo-S100B protein	kd	2.0000	uM
5-amino-6-methoxy-1,3-dimethylbenzimidazol-2-one	734556: Inhibition of human S100B/human TAMRA-p53(367-388) interaction by fluorescence polarization assay	ki	3.6000	uM
4-[4-[(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)sulfamoyl]anilino]-4-oxobutanoic acid	238034: Binding to holo-S100B protein	kd	4.5000	uM
2-(2-benzoyl-4-chlorophenyl)-1-(diaminomethylidene)guanidine	238034: Binding to holo-S100B protein	kd	4.5000	uM
4-N,4-N-diethyl-2-methylbenzene-1,4-diamine	734556: Inhibition of human S100B/human TAMRA-p53(367-388) interaction by fluorescence polarization assay	ki	5.0000	uM
2-[3-(tert-butylcarbamoyl)phenyl]-1,3-dioxoisoindole-5-carboxylic acid	238034: Binding to holo-S100B protein	kd	8.1000	uM

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
Tretinoin	decreases expression, decreases reaction, increases expression, increases secretion	4
trichostatin A	affects cotreatment, increases expression	3
Paraquat	affects expression, increases expression	3
Panobinostat	increases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	increases expression, decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
tungsten carbide	affects cotreatment, decreases expression	1
urushiol	increases expression, increases secretion	1
protocatechualdehyde	decreases reaction, increases expression, affects localization, increases phosphorylation	1
bisphenol A	affects cotreatment, decreases expression	1
diphenyleneiodonium	decreases reaction, increases expression	1
lead acetate	decreases expression	1
polysaccharide-K	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
perfluorooctanoic acid	increases expression	1
nickel sulfate	decreases expression	1
hydroquinone	increases expression, increases secretion	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	decreases expression	1
entinostat	increases expression	1
3-(4-methylphenylsulfonyl)-2-propenenitrile	decreases reaction, increases degradation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
LR-90	affects localization, decreases reaction, increases degradation, increases expression	1
2-(8-quinolinoxy)propionic acid	decreases reaction, increases expression	1
anatoxin a	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, increases expression	1
monascin	increases reaction, decreases expression, decreases reaction, affects localization, increases expression	1
MRK 003	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2341090	Binding	Inhibition of human S100B/humanTAMRA-p53(367-388) interaction by In situ proximity ligation assay	Identification of small-molecule inhibitors of the human S100B-p53 interaction and evaluation of their activity in human melanoma cells. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C4P7	WAe009-A-94	Embryonic stem cell	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.