MBP

Summary

MBP (myelin basic protein, HGNC:6925) is a protein-coding gene on chromosome 18q23, encoding Myelin basic protein (P02686). The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS.

The protein encoded by the classic MBP gene is a major constituent of the myelin sheath of oligodendrocytes and Schwann cells in the nervous system. However, MBP-related transcripts are also present in the bone marrow and the immune system. These mRNAs arise from the long MBP gene (otherwise called “Golli-MBP”) that contains 3 additional exons located upstream of the classic MBP exons. Alternative splicing from the Golli and the MBP transcription start sites gives rise to 2 sets of MBP-related transcripts and gene products. The Golli mRNAs contain 3 exons unique to Golli-MBP, spliced in-frame to 1 or more MBP exons. They encode hybrid proteins that have N-terminal Golli aa sequence linked to MBP aa sequence. The second family of transcripts contain only MBP exons and produce the well characterized myelin basic proteins. This complex gene structure is conserved among species suggesting that the MBP transcription unit is an integral part of the Golli transcription unit and that this arrangement is important for the function and/or regulation of these genes.

Source: NCBI Gene 4155 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 54 total — 2 pathogenic
• MANE Select transcript: NM_001025101

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6925
Approved symbol	MBP
Name	myelin basic protein
Location	18q23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000197971
Ensembl biotype	protein_coding
OMIM	159430
Entrez	4155

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 22 protein_coding, 10 protein_coding_CDS_not_defined, 9 nonsense_mediated_decay, 8 retained_intron

ENST00000354542, ENST00000355994, ENST00000359645, ENST00000382582, ENST00000397860, ENST00000397863, ENST00000397865, ENST00000397866, ENST00000397868, ENST00000397869, ENST00000397875, ENST00000447114, ENST00000459948, ENST00000467108, ENST00000473302, ENST00000482445, ENST00000483025, ENST00000484548, ENST00000487778, ENST00000490319, ENST00000490754, ENST00000493247, ENST00000493623, ENST00000495162, ENST00000497479, ENST00000498683, ENST00000526111, ENST00000527041, ENST00000527975, ENST00000528160, ENST00000531144, ENST00000533278, ENST00000577755, ENST00000578193, ENST00000578715, ENST00000578873, ENST00000579129, ENST00000580402, ENST00000580473, ENST00000581179, ENST00000581878, ENST00000582282, ENST00000583118, ENST00000583266, ENST00000583474, ENST00000583798, ENST00000585201, ENST00000585216, ENST00000673800

RefSeq mRNA: 6 — MANE Select: NM_001025101 NM_001025081, NM_001025090, NM_001025092, NM_001025100, NM_001025101, NM_002385

CCDS: CCDS12011, CCDS32847, CCDS42448, CCDS42449, CCDS42450

Canonical transcript exons

ENST00000355994 — 9 exons

Exon	Start	End
ENSE00001421865	77132580	77132783
ENSE00003476635	76989956	76990060
ENSE00003479882	77105211	77105286
ENSE00003487874	76978833	76980471
ENSE00003502747	77066298	77066385
ENSE00003523858	76988877	76988912
ENSE00003537820	76988495	76988527
ENSE00003605230	76984775	76984894
ENSE00003895863	77016832	77017268

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 100.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 577.1083 / max 73668.5829, expressed in 1495 samples.

FANTOM5 promoters (56 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172567	523.7803	190
172610	23.1105	1394
172548	2.9116	93
172549	2.1749	85
172526	2.0567	79
172547	1.9319	87
172565	1.8271	87
172609	1.8196	649
172611	1.3124	322
172546	1.2917	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cranial nerve II	UBERON:0000941	100.00	gold quality
pons	UBERON:0000988	100.00	gold quality
medulla oblongata	UBERON:0001896	100.00	gold quality
subthalamic nucleus	UBERON:0001906	100.00	gold quality
substantia nigra pars reticulata	UBERON:0001966	100.00	gold quality
inferior olivary complex	UBERON:0002127	100.00	gold quality
lateral globus pallidus	UBERON:0002476	100.00	gold quality
inferior vagus X ganglion	UBERON:0005363	100.00	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	100.00	gold quality
superior vestibular nucleus	UBERON:0007227	100.00	gold quality
globus pallidus	UBERON:0001875	99.99	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.99	gold quality
substantia nigra pars compacta	UBERON:0001965	99.99	gold quality
corpus callosum	UBERON:0002336	99.99	gold quality
medial globus pallidus	UBERON:0002477	99.99	gold quality
ventral tegmental area	UBERON:0002691	99.99	gold quality
middle frontal gyrus	UBERON:0002702	99.99	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.99	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.99	gold quality
amygdala	UBERON:0001876	99.96	gold quality
olfactory bulb	UBERON:0002264	99.96	gold quality
putamen	UBERON:0001874	99.95	gold quality
hypothalamus	UBERON:0001898	99.95	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.95	gold quality
parietal lobe	UBERON:0001872	99.94	gold quality
postcentral gyrus	UBERON:0002581	99.94	gold quality
nucleus accumbens	UBERON:0001882	99.92	gold quality
right frontal lobe	UBERON:0002810	99.91	gold quality
frontal pole	UBERON:0002795	99.90	gold quality
prefrontal cortex	UBERON:0000451	99.89	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	16053.97
E-HCAD-25	yes	7615.10
E-GEOD-135922	yes	4936.79
E-GEOD-180759	yes	4612.38
E-HCAD-30	yes	4475.29
E-HCAD-35	yes	3764.69
E-GEOD-81383	yes	1869.72
E-CURD-122	yes	41.28
E-MTAB-5061	no	3.56
E-CURD-112	no	2.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting MBP, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-12122	99.56	69.33	1672

Literature-anchored findings (GeneRIF, showing 40)

• Association of MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland. (PMID:12618862)
• Findings of secreted MBP epitopes in all tested sera from healthy donors and from multiple sclerosis patients as well as in sera from normal human cord blood provide insights into the establishment of central and peripheral tolerance to MBP products. (PMID:12965257)
• Decreased expression of a number of myelin-related genes, including myelin basic protein (MBP), proteolipid protein (PLP), and myelin-associated oligodendrocyte basic protein (MOBP) was noted in nucleus accumbens of cocaine abusers (PMID:15009677)
• discovered epitope-specific antibody-mediated degradation of MBP suggests a mechanistic explanation of the slow development of neurodegeneration associated with multiple sclerosis (PMID:16387849)
• Results suggest that human trypsin 4 may be one of the candidate proteases involved in the pathomechanism of multiple sclerosis via cleavage of myelin basic protein. (PMID:16412431)
• Golli-MBP deletion or duplication is rarely involved in inherited defects of myelin formation. (PMID:16441258)
• Immunodomonant MBP 84-106 actively associates with Hsp70 from multiple sclerosis white matter. The complex is higly immunogenic with adjuvant-like effects stimulating MBP peptide-specific T cell lines to respond to sub-optimal concentrations of peptide. (PMID:16842822)
• myelin basic protein charge isomer, component-8, was more susceptible to stromelysin-1 cleavage than myelin basic protein component-1; increased susceptibility of component-8 to proteolytic digestion may play a role in pathogenesis of multiple sclerosis (PMID:16871440)
• both the spectrum of MBP found, as well as the MOGIgd epitopes recognized by peripheral blood T cells in multiple sclerosis, appear to be similar for childhood/juvenile-onset and adult-onset patients (PMID:16900754)
• MBP inhibits the fibril assembly of cerebral amyloid angiopathy mutant amyloid beta-protein (Abeta). (PMID:17259179)
• EGO is a novel ncRNA gene expressed during eosinophil development and is necessary for normal MBP and EDN transcript expression. (PMID:17351112)
• There was a statistically significant inverse correlation between myelin basic protein (MBP) expression and proliferation index in pilocytic astrocytomas; expression of MBP was also related to progression-free survival. (PMID:17690840)
• Myelin basic protein and p25alpha colocalize in myelin in normal human brains. (PMID:17823288)
• MBP-specific CD4+, CD8+, and NK cells might be involved in the direct impairment of neuronal cell bodies and myelin sheaths in multiple sclerosis. (PMID:18067995)
• Results give a detailed structural insight into the interaction of calmodulin with a C-terminal segment of a major myelin protein, the myelin basic protein. (PMID:18284662)
• Myelin cross-reactive T cells produced IFN-gamma, but differed from EBNA1-monospecific cells in their capability to produce interleukin-2. (PMID:18663124)
• T cells specific for low-affinity MHC-binding hMBP epitopes and hMBP82-100-specific type B T cells were highly encephalitogenic. (PMID:18713991)
• Peripheral activation of myelin basic protein-specific CD4-positive T cells in draining lymph nodes is an early event in the development of autoimmune encephalitis (EAE) in healthy pre-EAE transgenic mice. (PMID:18802067)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• BMP may have a role in citrullination of self-antigens that may potentially trigger disease in susceptible individuals (PMID:19053745)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• Suggest that golli-MBP is a possible susceptibility gene for schizophrenia in the Jewish Ashkenazi population. (PMID:19154657)
• MBP is capable of inhibiting the beta-sheet fibrillar assembly of the normal Abeta42 peptide and may play a role in regulating the deposition of Abeta42, and thereby also may regulate the early formation of amyloid plaques in Alzheimer’s disease. (PMID:19385666)
• solution structural motif of MBP83-99 (immunodominant epitope) performed using 2D 1H-NMR spectroscopy in dimethyl sulfoxide; residues implicated in T-cell receptor recognition in multiple sclerosis are solvent exposed (PMID:19468823)
• Golli-MBP has a clear effect on oligodendrocyte precursor cell development via modulating multiple divalent calcium ion regulatory events through voltage-operated- and store-operated calcium channels. (PMID:19570024)
• MBP is not specific marker for tumors of oligodendroglial origin, but determination of relative levels of MBP and GFAP mRNAs may be useful for glial tumors recognition. (PMID:19663312)
• amyloid beta protein is degraded by purified myelin basic protein (PMID:19692707)
• The 21.5 kDa MBP promotes the proliferation of HepG-2 cells and blocks apoptosis. (PMID:19950581)
• Three single nucleotide polymorphisms (STAT6 rs703817, C1qG rs17433222, and MBP rs3794845) were found to be significantly associated with childhood leukemia risk in Koreans. (PMID:20438785)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• Data show that Golli interacts with the C-terminal domain of STIM1 in both in vitro and in vivo binding assays and this interaction may be modulated by the intracellular Ca(2+) concentration. (PMID:20629634)
• Data show that MBP purified from either brain or a bacterial recombinant expression system comparably bound to Abeta and inhibited Abeta fibril assembly indicating that post-translational modifications are not required for this activity. (PMID:20807757)
• Maltose-binding protein enhances secretion of recombinant human granzyme B accompanied by in vivo processing of a precursor MBP fusion protein (PMID:21203542)
• our findings suggest a key role for classical MBP proteins in regulating voltage-gated Ca(2+) channels at the plasma membrane of oligodendroglial cells (PMID:21312222)
• Type I spiral ganglion nerve somata were surrounded by “satellite glial cells” that lacked expression of MBP indicating that these cells are non-myelinating. Myelination pattern in human spiral ganglion is different from that in other species’. (PMID:21601398)
• The GroEL/GroES chamber thus appears to function passively toward Double mutant MBP refolding (PMID:21609718)
• a genetic study in rheumatoid arthritis implicating MBP as a potential autoantigen and its involvement in pathogenesis of the disease (PMID:21673997)
• Elevated levels of cerebrospinal fluid MBP seem to reflect a subcortical profile among patients with vascular dementia compared to those with mixed dementia. (PMID:21860087)
• Molecular Dynamics simulations of the MuBetaRho 83-99 (Phe91) and MuBetaRho 83-99 (Tyr91) peptide analogues in complex with HLA-DR2 (DRA, DRB1*1501) and T-cell receptors were performed. (PMID:21898163)
• Fractional anisotropy in the centrum semiovale or pyramidal tract offers a quantitative indicator of the extent of demyelination in damaged cerebral white matter during the subacute phase in carbon monoxide-poisoned patients. (PMID:22258479)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mbpa	ENSDARG00000036186
mus_musculus	Mbp	ENSMUSG00000041607
rattus_norvegicus	Mbp	ENSRNOG00000016516

Protein

Protein identifiers

Myelin basic protein — P02686 (reviewed: P02686)

Alternative names: Myelin A1 protein, Myelin membrane encephalitogenic protein

All UniProt accessions (23): A8MZH3, C9J6H1, E9PJ72, E9PKX9, E9PLQ9, E9PLU9, E9PMR5, E9PNZ1, E9PQE7, E9PSE2, P02686, F5H7N4, F8WEU6, H0YEA2, H0YF02, H7BYR8, J3KS94, J3KT01, J3KT34, J3QKL5, J3QKN5, J3QL64, J3QQK6

UniProt curated annotations — full annotation on UniProt →

Function. The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation.

Subunit / interactions. Homodimer. Isoform 3 exists as a homodimer.

Subcellular location. Myelin membrane Nucleus.

Tissue specificity. MBP isoforms are found in both the central and the peripheral nervous system, whereas Golli-MBP isoforms are expressed in fetal thymus, spleen and spinal cord, as well as in cell lines derived from the immune system.

Post-translational modifications. Several charge isomers of MBP; C1 (the most cationic, least modified, and most abundant form), C2, C3, C4, C5, C6, C7, C8-A and C8-B (the least cationic form); are produced as a result of optional PTM, such as phosphorylation, deamidation of glutamine or asparagine, arginine citrullination and methylation. C8-A and C8-B contain each two mass isoforms termed C8-A(H), C8-A(L), C8-B(H) and C8-B(L), (H) standing for higher and (L) for lower molecular weight. C3, C4 and C5 are phosphorylated. The ratio of methylated arginine residues decreases during aging, making the protein more cationic. The N-terminal alanine is acetylated (isoform 3, isoform 4, isoform 5 and isoform 6). Arg-241 was found to be 6% monomethylated and 60% symmetrically dimethylated. Proteolytically cleaved in B cell lysosomes by cathepsin CTSG which degrades the major immunogenic MBP epitope and prevents the activation of MBP-specific autoreactive T cells. Phosphorylated by TAOK2, VRK2, MAPK11, MAPK12, MAPK14 and MINK1.

Disease relevance. The reduction in the surface charge of citrullinated and/or methylated MBP could result in a weakened attachment to the myelin membrane. This mechanism could be operative in demyelinating diseases such as chronical multiple sclerosis (MS), and fulminating MS (Marburg disease).

Miscellaneous. Contains a non-traditional PY nuclear localization signal. Mutagenesis of Cys-81 to Ser prevents dimerization.

Similarity. Belongs to the myelin basic protein family.

Isoforms (6)

UniProt ID	Names	Canonical?
P02686-1	1, Golli-MBP1, HOG7	yes
P02686-2	2, Golli-MBP2, HOG5
P02686-3	3, MBP1, 21.5 kDa
P02686-4	4, MBP2, 20.2 kDa
P02686-5	5, MBP3, 18.5 kDa
P02686-6	6, MBP4, 17.2 kDa

RefSeq proteins (6): NP_001020252, NP_001020261, NP_001020263, NP_001020271, NP_001020272, NP_002376 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000548	Myelin_BP	Family

Pfam: PF01669

UniProt features (60 total): modified residue 39, compositionally biased region 5, region of interest 4, splice variant 4, initiator methionine 4, site 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1FV1	X-RAY DIFFRACTION	1.9
1K2D	X-RAY DIFFRACTION	2.2
1BX2	X-RAY DIFFRACTION	2.6
1ZGL	X-RAY DIFFRACTION	2.8
1HQR	X-RAY DIFFRACTION	3.2
1YMM	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02686-F1	54.55	0.00

Functional residue map

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

Catalytic / active sites (2): 224–225 (cleavage; by ctsg); 248–249 (cleavage; by ctsg)

Post-translational modifications (39): 96, 141, 146, 148, 151, 153, 154, 159, 165, 167, 169, 174, 177, 183, 190, 199, 203, 210, 214, 229 …

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
R-HSA-1266738	Developmental Biology
R-HSA-9675108	Nervous system development

MSigDB gene sets: 357 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOCC_CELL_SURFACE, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, MODULE_66, WEI_MYCN_TARGETS_WITH_E_BOX, SOX9_B1, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, MARTINEZ_RB1_TARGETS_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_ENSHEATHMENT_OF_NEURONS, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, OCT1_07

GO Biological Process (16): immune response (GO:0006955), chemical synaptic transmission (GO:0007268), central nervous system development (GO:0007417), sensory perception of sound (GO:0007605), axon ensheathment (GO:0008366), response to toxic substance (GO:0009636), myelin assembly (GO:0032288), myelination (GO:0042552), membrane organization (GO:0061024), MAPK cascade (GO:0000165), substantia nigra development (GO:0021762), positive regulation of interleukin-6 production (GO:0032755), negative regulation of heterotypic cell-cell adhesion (GO:0034115), maintenance of blood-brain barrier (GO:0035633), positive regulation of metalloendopeptidase activity (GO:1904685), positive regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000343)

GO Molecular Function (5): protease binding (GO:0002020), calmodulin binding (GO:0005516), lipid binding (GO:0008289), structural constituent of myelin sheath (GO:0019911), protein binding (GO:0005515)

GO Cellular Component (13): nucleus (GO:0005634), cytosol (GO:0005829), cell surface (GO:0009986), protein-containing complex (GO:0032991), internode region of axon (GO:0033269), neuronal cell body (GO:0043025), myelin sheath (GO:0043209), compact myelin (GO:0043218), synapse (GO:0045202), cell periphery (GO:0071944), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
binding	2
myelin sheath	2
immune system process	1
response to stimulus	1
anterograde trans-synaptic signaling	1
nervous system development	1
system development	1
sensory perception of mechanical stimulus	1
ensheathment of neurons	1
response to chemical	1
cellular component assembly involved in morphogenesis	1
myelination	1
axon ensheathment	1
cellular component organization	1
intracellular signaling cassette	1
midbrain development	1
neural nucleus development	1
positive regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
negative regulation of cell-cell adhesion	1
heterotypic cell-cell adhesion	1
regulation of heterotypic cell-cell adhesion	1
regulation of cell-cell adhesion involved in gastrulation	1
tissue homeostasis	1
metalloendopeptidase activity	1
positive regulation of endopeptidase activity	1
positive regulation of metallopeptidase activity	1
positive regulation of chemokine production	1
chemokine (C-X-C motif) ligand 2 production	1
regulation of chemokine (C-X-C motif) ligand 2 production	1
enzyme binding	1
protein binding	1
structural molecule activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular_component	1
main axon	1
somatodendritic compartment	1

Protein interactions and networks

STRING

2956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBP	CALML6	Q8TD86	987
MBP	CALML3	P27482	987
MBP	CALML5	Q9NZT1	987
MBP	CALML4	Q96GE6	987
MBP	MAG	P20916	986
MBP	CALM1	P02593	980
MBP	PLP1	P04400	962
MBP	MOG	Q16653	948
MBP	CNP	P09543	894
MBP	SLC26A3	P40879	861
MBP	MPZL1	O95297	859
MBP	GFAP	P14136	847
MBP	OLIG2	Q13516	827
MBP	CNTNAP1	P78357	816
MBP	GALC	P54803	814

IntAct

43 interactions, top by confidence:

A	B	Type	Score
APP	APBB1	psi-mi:“MI:0914”(association)	0.910
HLA-DRA	HLA-DRB1	psi-mi:“MI:0914”(association)	0.880
CTDSP1	MBP	psi-mi:“MI:0915”(physical association)	0.740
MBP	CTDSP1	psi-mi:“MI:0915”(physical association)	0.740
NCK1	NCK2	psi-mi:“MI:0914”(association)	0.730
HLA-DMA	HLA-DRA	psi-mi:“MI:0914”(association)	0.620
HLA-DRB1	HLA-DRA	psi-mi:“MI:0915”(physical association)	0.520
MBP	IDE	psi-mi:“MI:0915”(physical association)	0.500
ADRB2	MBP	psi-mi:“MI:2364”(proximity)	0.450
CCR1	MBP	psi-mi:“MI:2364”(proximity)	0.450
MBP	PTAFR	psi-mi:“MI:2364”(proximity)	0.450
MBP	ADRB2	psi-mi:“MI:0915”(physical association)	0.450
MBP	CCR1	psi-mi:“MI:0915”(physical association)	0.450
MBP	PTAFR	psi-mi:“MI:0915”(physical association)	0.450
MBP		psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
PBK	MBP	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MBP	PRMT10	psi-mi:“MI:0213”(methylation reaction)	0.440
NLN	MBP	psi-mi:“MI:0915”(physical association)	0.400
DUSP22	MBP	psi-mi:“MI:0915”(physical association)	0.400
MBP	TSC1	psi-mi:“MI:0915”(physical association)	0.370
PDGFRL	MBP	psi-mi:“MI:0915”(physical association)	0.370
PRNP	MBP	psi-mi:“MI:0914”(association)	0.350

BioGRID (174): MBP (Biochemical Activity), CTDSP1 (Two-hybrid), MBP (Biochemical Activity), MBP (Biochemical Activity), MBP (Biochemical Activity), MBP (Biochemical Activity), MBP (Synthetic Growth Defect), MBP (Biochemical Activity), MBP (Biochemical Activity), MBP (Affinity Capture-MS), MBP (Affinity Capture-MS), MBP (Biochemical Activity), MBP (Biochemical Activity), MBP (Biochemical Activity), MBP (Biochemical Activity)

ESM2 similar proteins: A0A140LFM6, A0A1B0GVH6, A1A4G5, A1CQN6, A7A241, A9RNY0, B0QZF7, B9UYK6, E9Q309, H0WFA5, O23372, O35413, O94875, P02686, P43587, Q0VFP3, Q0WL69, Q12912, Q17QQ9, Q1G3K8, Q32KY7, Q3UTJ2, Q499E5, Q4R309, Q4R881, Q4V7T5, Q56WM6, Q5E9A0, Q5PPL1, Q5R6I3, Q5VT06, Q62417, Q6AYU0, Q6DD19, Q6GP48, Q6H7U2, Q8K2H1, Q8L4M6, Q8NEY8, Q8NG27

Diamond homologs: P02686, P02687, P02688, P04370, P06906, P15720, P20939, P25188, P25274, P81558, P83487, P87346, P98190, Q91325, Q91439

SIGNOR signaling

26 interactions.

A	Effect	B	Mechanism
MAPK1	down-regulates	MBP	phosphorylation
MAPK3	down-regulates	MBP	phosphorylation
UHMK1	down-regulates	MBP	phosphorylation
MAPK1	unknown	MBP	phosphorylation
Gbeta	down-regulates	MBP	phosphorylation
ERK1/2	down-regulates	MBP	phosphorylation
SMO	“up-regulates quantity”	MBP	“transcriptional regulation”
PRKCA	unknown	MBP	phosphorylation
PRKACA	unknown	MBP	phosphorylation
MBP	up-regulates	Myelination
RXRG	“up-regulates quantity”	MBP	“transcriptional regulation”
CNP	“down-regulates activity”	MBP

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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
Class A/1 (Rhodopsin-like receptors)	5	18.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	31
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1808639	GRCh37/hg19 18q21.2-23(chr18:53624405-78014123)x1	Pathogenic
816057	GRCh37/hg19 18q22.3-23(chr18:70383594-78014123)x1	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1984 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:76989966:A:G	F224S	0.997
18:77017087:G:C	F107L	0.996
18:77017087:G:T	F107L	0.996
18:77017089:A:G	F107L	0.996
18:76989969:A:G	F223S	0.995
18:77017098:C:G	D104H	0.993
18:77017123:A:C	F95L	0.993
18:77017123:A:T	F95L	0.993
18:77017125:A:G	F95L	0.993
18:77017088:A:G	F107S	0.992
18:77017093:G:C	N105K	0.992
18:77017093:G:T	N105K	0.992
18:76989968:G:C	F223L	0.991
18:76989968:G:T	F223L	0.991
18:76989970:A:G	F223L	0.991
18:77017084:T:A	K108N	0.990
18:77017084:T:G	K108N	0.990
18:77017088:A:C	F107C	0.990
18:77017102:C:A	R102S	0.990
18:77017102:C:G	R102S	0.990
18:76989966:A:C	F224C	0.989
18:77016884:A:T	I175N	0.989
18:77017124:A:G	F95S	0.988
18:76984782:A:G	F288S	0.987
18:77017097:T:G	D104A	0.986
18:76989969:A:C	F223C	0.985
18:77017097:T:A	D104V	0.985
18:76989965:G:C	F224L	0.984
18:76989965:G:T	F224L	0.984
18:76989967:A:G	F224L	0.984

dbSNP variants (sampled 300 via entrez): RS1000001600 (18:77073734 T>G), RS1000003982 (18:77068016 C>T), RS1000010918 (18:77035319 G>A), RS1000041881 (18:76993584 T>G), RS1000061231 (18:77068203 G>C), RS1000088658 (18:77066972 T>C), RS1000089544 (18:77080811 G>A), RS1000092352 (18:77099714 G>T), RS1000105489 (18:77117519 A>G), RS1000112133 (18:77029787 CACACAA>C,CACACAAACACAA), RS1000117395 (18:77082605 T>C), RS1000121885 (18:77029762 T>A,C), RS1000140650 (18:77067259 T>C), RS1000141155 (18:76994688 T>C), RS1000162105 (18:77133020 C>A)

Disease associations

OMIM: gene MIM:159430 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	4
Tetrachlorodibenzodioxin	increases expression	3
Tretinoin	decreases expression, increases expression	3
trichostatin A	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Methotrexate	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
TL8-506	affects cotreatment, increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
lead acetate	increases abundance, increases expression	1
sodium arsenate	increases abundance, increases expression	1
terbufos	increases methylation	1
arsenite	affects binding, decreases reaction	1
sodium bichromate	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
2-ethylhexyldiphenylphosphate	decreases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
manganese chloride	increases expression	1
tri-o-cresyl phosphate	decreases expression	1
ochratoxin A	increases expression	1
benzo(e)pyrene	increases methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SX52	HAP1 MBP (-) 1	Cancer cell line	Male
CVCL_XQ32	HAP1 MBP (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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