MAP1B

Summary

MAP1B (microtubule associated protein 1B, HGNC:6836) is a protein-coding gene on chromosome 5q13.2, encoding Microtubule-associated protein 1B (P46821). Facilitates tyrosination of alpha-tubulin in neuronal microtubules.

This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The product of this gene is a precursor polypeptide that presumably undergoes proteolytic processing to generate the final MAP1B heavy chain and LC1 light chain. Gene knockout studies of the mouse microtubule-associated protein 1B gene suggested an important role in development and function of the nervous system.

Source: NCBI Gene 4131 — RefSeq curated summary.

At a glance

• Gene–disease (curated): periventricular nodular heterotopia (Strong, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 644 total — 18 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 54
• Druggable target: yes
• MANE Select transcript: NM_005909

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6836
Approved symbol	MAP1B
Name	microtubule associated protein 1B
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MAP5, PPP1R102
Ensembl gene	ENSG00000131711
Ensembl biotype	protein_coding
OMIM	157129
Entrez	4131

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000296755, ENST00000504183, ENST00000504492, ENST00000511641, ENST00000512974, ENST00000513526

RefSeq mRNA: 2 — MANE Select: NM_005909 NM_001324255, NM_005909

CCDS: CCDS4012

Canonical transcript exons

ENST00000296755 — 7 exons

Exon	Start	End
ENSE00000752179	72193866	72200367
ENSE00000752180	72203563	72203801
ENSE00001013163	72115698	72115799
ENSE00001126317	72107475	72107715
ENSE00001556259	72205084	72209565
ENSE00003493109	72183743	72183825
ENSE00003612092	72186614	72186754

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 183.3563 / max 27951.1888, expressed in 1474 samples.

FANTOM5 promoters (53 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56884	64.2360	1391
56882	37.3327	1370
56932	12.5360	978
56885	10.6453	1159
56918	8.1259	908
56927	6.8126	754
56891	6.0720	456
56883	5.1406	1107
56926	2.7871	519
56936	2.7693	525

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.97	gold quality
substantia nigra pars compacta	UBERON:0001965	99.95	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.93	gold quality
middle temporal gyrus	UBERON:0002771	99.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.93	gold quality
superior vestibular nucleus	UBERON:0007227	99.91	gold quality
pons	UBERON:0000988	99.90	gold quality
parietal lobe	UBERON:0001872	99.89	gold quality
lateral globus pallidus	UBERON:0002476	99.89	gold quality
postcentral gyrus	UBERON:0002581	99.89	gold quality
dorsal root ganglion	UBERON:0000044	99.86	gold quality
entorhinal cortex	UBERON:0002728	99.86	gold quality
ventral tegmental area	UBERON:0002691	99.84	gold quality
trigeminal ganglion	UBERON:0001675	99.80	gold quality
inferior vagus X ganglion	UBERON:0005363	99.79	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.77	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.76	gold quality
orbitofrontal cortex	UBERON:0004167	99.76	gold quality
medulla oblongata	UBERON:0001896	99.75	gold quality
cranial nerve II	UBERON:0000941	99.73	gold quality
superior frontal gyrus	UBERON:0002661	99.70	gold quality
subthalamic nucleus	UBERON:0001906	99.69	gold quality
CA1 field of hippocampus	UBERON:0003881	99.65	gold quality
globus pallidus	UBERON:0001875	99.63	gold quality
medial globus pallidus	UBERON:0002477	99.59	gold quality
cortical plate	UBERON:0005343	99.58	gold quality
urethra	UBERON:0000057	99.52	gold quality
saphenous vein	UBERON:0007318	99.47	gold quality
blood vessel layer	UBERON:0004797	99.31	gold quality
cauda epididymis	UBERON:0004360	99.27	gold quality

Single-cell (SCXA)

Detected in 43 experiment(s), a significant marker in 30.

Experiment	Marker?	Max mean expression
E-MTAB-6911	yes	16711.30
E-HCAD-56	yes	4939.30
E-MTAB-11121	yes	4852.51
E-MTAB-7051	yes	4349.86
E-GEOD-81608	yes	4129.51
E-HCAD-35	yes	4014.70
E-GEOD-135922	yes	3477.91
E-HCAD-30	yes	3431.96
E-MTAB-6108	yes	3079.09
E-MTAB-8221	yes	2304.76
E-MTAB-7407	yes	2104.21
E-MTAB-6701	yes	1980.20
E-GEOD-84465	yes	1606.14
E-CURD-126	yes	789.28
E-MTAB-5061	yes	699.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL11A, FOXA2, MYOG, TP53

miRNA regulators (miRDB)

256 targeting MAP1B, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-32-5P	99.98	75.21	1964

Literature-anchored findings (GeneRIF, showing 29)

• MAP1B action is modulated by mapmodulin/leucine-rich acidic nuclear protein (PMID:12807913)
• Complexes (MAP1B heavy chain-MAP1A light chain) form through interaction of homologous domains conserved in heavy and light chains of MAP1A and MAP1B. Conserved domains of the MAP1A and MAP1B light chains account for formation of light chain heterodimers. (PMID:16996626)
• The light chain (LC1) of microtubule-associated protein 1B (MAP1B)-5-HT(3A) receptor interaction contributes to a mechanism that regulates receptor desensitization kinetics. (PMID:18063656)
• Amyloid-beta 1-42 binds to a peptide comprising the microtubule binding domain of the heavy chain of microtubule-associated protein 1B by the screening of a human brain cDNA library expressed on M13 phage. (PMID:18079022)
• a role for MAP1B in DAPK-1-dependent signaling in autophagy and membrane blebbing. (PMID:18195017)
• MAP1B light chain can interact with the tumor suppressor p53. (PMID:18656471)
• a new protein involved in the terminal differentiation of odontoblasts (PMID:19567321)
• These observations define a new and crucial function of MAP1B that is required for efficient cross-talk between microtubules and the actin cytoskeleton during neuronal polarization. (PMID:20719958)
• We suggest a role for Stau2 in the generation and regulation of Map1b mRNA containing granules that are required for mGluR-long-term depression (PMID:21508097)
• An interaction between MAP1B LC1 and the ubiquitin-conjugating enzyme UBE2L3. (PMID:24566975)
• signal transduction pathways downstream of 5-HT6R are regulated by MAP1B, which might play a role in 5-HT6R-mediated signaling in the brain. (PMID:24614691)
• Yeast-two-hybrid screening using human LRRK2 kinase domain as bait identified microtubule associated protein 1B (MAP1B) as a LRRK2 interactor. (PMID:24754922)
• Localization of MAP1B is altered in amyotrophic lateral sclerosis spinal cords in a transgenic animal model. (PMID:25429138)
• The the MAP1B-LC1-mediated regulation most likely involves an internalization of the channels via a dynamin and clathrin-dependent pathway. (PMID:25483588)
• KIRREL3 interacting proteins MAP1B and MYO16 are potential candidates for intellectual disability and autism spectrum disorder. (PMID:25902260)
• The found of this study suggested that possible roles of MAP1B genes in working memory performance in ADHD patients (PMID:26233433)
• These results suggest that a change in the intracellular calcium level plays a role in regulation of the secretory pathway via interaction of ALG-2 with MISSL and MAP1B. (PMID:28864773)
• High MAP1B expression is associated with resistance to mTOR inhibition in glioblastoma. (PMID:29136244)
• MAP1B heavy chain has a unique binding site for a calcium-binding protein ALG-2. (PMID:29432744)
• All of the patients with a microtubule associated protein 1B (MAP1B) variant had a similar brain abnormality, and at least one of the parents who transmitted the variant to their child was also similarly affected. (PMID:29738522)
• MAP1B-LC1 links microtubules and Stx17 in fed cells, and starvation causes the dephosphorylation of MAP1B-LC1 at Thr217, allowing Stx17 to dissociate from MAP1B-LC1 and bind to Atg14L. (PMID:29925525)
• Calpain-10 regulates actin dynamics by proteolysis of microtubule-associated protein 1B (PMID:30425305)
• These neuritic defects result from impaired Nrf2 activity on antioxidant response elements (AREs) localized to a microtubule-associated protein (Map1b) gene enhancer and are rescued by forced expression of Map1b as well as by both Nrf2 overexpression and pharmaceutical activation in Parkinson’s disease (PD) neurons (PMID:31235589)
• Knockdown of microtubule-associated protein 1B light chain (MAP 1B-LC1) represses E-cadherin downregulation, vimentin upregulation and actin filament remodeling, decreases cell migration and invasion during TGF-beta1-induced epithelial to mesenchymal transition (EMT) in A549 cells. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) promotes the EMT of lung cancer cells induced by TGF-beta1 through interacting with MAP… (PMID:31492158)
• Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss. (PMID:33268592)
• Epilepsy phenotypes associated with MAP1B-related brain malformations. (PMID:33772511)
• The miR-223-3p/MAP1B axis aggravates TGF-beta-induced proliferation and migration of BPH-1 cells. (PMID:33839256)
• Elevated levels of FMRP-target MAP1B impair human and mouse neuronal development and mouse social behaviors via autophagy pathway. (PMID:37365192)
• A MAP1B-cortactin-Tks5 axis regulates TNBC invasion and tumorigenesis. (PMID:38353696)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	map1b	ENSDARG00000060434
mus_musculus	Map1b	ENSMUSG00000052727
rattus_norvegicus	Map1b	ENSRNOG00000017428

Paralogs (2): MAP1S (ENSG00000130479), MAP1A (ENSG00000166963)

Protein

Protein identifiers

Microtubule-associated protein 1B — P46821 (reviewed: P46821)

All UniProt accessions (5): D6RA32, D6RA40, D6RCL2, D6RGJ3, P46821

UniProt curated annotations — full annotation on UniProt →

Function. Facilitates tyrosination of alpha-tubulin in neuronal microtubules. Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension. Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing.

Subunit / interactions. 3 different light chains, LC1 (a cleavage product of MAP1B), LC2 (a cleavage product of MAP1A) and LC3 (produced by one of the MAP1LC3 genes), can associate with the MAP1A or MAP1B heavy chains. LC1 interacts with the amino-terminal region of MAP1B. Interacts with ANP32A and TIAM2. Interacts with the tubulin tyrosine TTL. Interacts (via C-terminus) with GAN (via Kelch domains). Interacts (via N-terminus) with DAPK1. Interacts with TMEM185A. Interacts with MAP1LC3B. Interacts with KIRREL3. Interacts (via C-terminus) with ELAVL4; the interaction contributes to the association of ELAVL4 with microtubules. Interacts with ELAVL2 and ELAVL3.

Subcellular location. Cytoplasm. Cytoskeleton. Synapse. Cell projection. Dendritic spine Cytoplasm.

Post-translational modifications. LC1 is generated from MAP1B by proteolytic processing. S-nitrosylation at Cys-2464 enhances interaction with microtubules, and may act as an effector modification for neuronal nitric oxide synthase control of growth-cone size, growth-cone collapse and axon retraction.

Disease relevance. Periventricular nodular heterotopia 9 (PVNH9) [MIM:618918] A form of periventricular nodular heterotopia, a disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches. PVNH9 is an autosomal dominant disorder with incomplete penetrance, characterized by impaired intellectual development, cognitive defects, learning disabilities, and behavior abnormalities. Some patients develop seizures. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal dominant, 83 (DFNA83) [MIM:619808] A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DNFA83 is characterized by progressive, mild to profound hearing loss. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. Has a highly basic region with many copies of the sequence KKEE and KKEI/V, repeated but not at fixed intervals, which is responsible for the binding of MAP1B to microtubules.

Similarity. Belongs to the MAP1 family.

RefSeq proteins (2): NP_001311184, NP_005900* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000102	MAP1B_neuraxin	Repeat
IPR026074	MAP1	Family
IPR056617	MAP1B/S_N	Domain
IPR057480	MAP1A/B/S-like_MBL	Domain

Pfam: PF00414, PF23415, PF25281

UniProt features (175 total): modified residue 101, compositionally biased region 34, sequence variant 15, region of interest 11, repeat 10, chain 3, initiator methionine 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46821-F1	46.18	0.18

Functional residue map

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

Post-translational modifications (101): 1282, 1298, 1312, 1322, 1324, 1326, 1328, 1330, 1339, 1376, 1378, 1387, 1389, 1396, 1400, 1408, 1410, 1427, 1438, 1443 …

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9833110	RSV-host interactions
R-HSA-1643685	Disease
R-HSA-5663205	Infectious disease
R-HSA-9820952	Respiratory Syncytial Virus Infection Pathway
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (33): microtubule cytoskeleton organization (GO:0000226), microtubule bundle formation (GO:0001578), neuron migration (GO:0001764), negative regulation of microtubule depolymerization (GO:0007026), axonogenesis (GO:0007409), synapse assembly (GO:0007416), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), response to carbohydrate (GO:0009743), peripheral nervous system axon regeneration (GO:0014012), dendrite development (GO:0016358), response to insecticide (GO:0017085), developmental maturation (GO:0021700), regulation of microtubule depolymerization (GO:0031114), positive regulation of microtubule polymerization (GO:0031116), neuron projection development (GO:0031175), response to estradiol (GO:0032355), negative regulation of intracellular transport (GO:0032387), response to vitamin A (GO:0033189), positive regulation of neuron differentiation (GO:0045666), positive regulation of axon extension (GO:0045773), mitochondrion transport along microtubule (GO:0047497), axon extension (GO:0048675), induction of synaptic plasticity by chemical substance (GO:0051915), establishment of monopolar cell polarity (GO:0061162), cellular response to growth factor stimulus (GO:0071363), cellular response to peptide hormone stimulus (GO:0071375), odontoblast differentiation (GO:0071895), regulation of postsynapse assembly (GO:0150052), nervous system development (GO:0007399), response to nutrient levels (GO:0031667), neuron development (GO:0048666), response to axon injury (GO:0048678)

GO Molecular Function (6): actin binding (GO:0003779), structural molecule activity (GO:0005198), phospholipid binding (GO:0005543), microtubule binding (GO:0008017), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (24): photoreceptor outer segment (GO:0001750), cytosol (GO:0005829), microtubule (GO:0005874), microtubule associated complex (GO:0005875), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), axon (GO:0030424), dendrite (GO:0030425), growth cone (GO:0030426), somatodendritic compartment (GO:0036477), neuronal cell body (GO:0043025), varicosity (GO:0043196), dendritic spine (GO:0043197), perikaryon (GO:0043204), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), apical dendrite (GO:0097440), basal dendrite (GO:0097441), hippocampal mossy fiber (GO:0097457), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Respiratory Syncytial Virus Infection Pathway	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
dendrite	3
microtubule depolymerization	2
response to oxygen-containing compound	2
response to lipid	2
binding	2
cytoplasm	2
microtubule cytoskeleton	2
neuron projection	2
cytoskeleton organization	1
microtubule-based process	1
microtubule cytoskeleton organization	1
cell migration	1
generation of neurons	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
nervous system development	1
cell junction assembly	1
synapse organization	1
response to chemical	1
response to external stimulus	1
response to abiotic stimulus	1
axon regeneration	1
neuron projection development	1
anatomical structure development	1
response to toxic substance	1
developmental process	1
regulation of microtubule polymerization or depolymerization	1
regulation of protein depolymerization	1
regulation of supramolecular fiber organization	1
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
positive regulation of protein polymerization	1
microtubule polymerization	1
positive regulation of supramolecular fiber organization	1

Protein interactions and networks

STRING

2882 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP1B	GAN	Q9H2C0	981
MAP1B	SQSTM1	Q13501	970
MAP1B	FMR1	Q06787	941
MAP1B	BECN1	Q14457	925
MAP1B	ATG12	O94817	909
MAP1B	F5GZY7	F5GZY7	901
MAP1B	GABARAPL2	P60520	899
MAP1B	MAP1LC3A	Q9H492	891
MAP1B	MAP1LC3B	Q9GZQ8	880
MAP1B	ATG5	Q9H1Y0	867
MAP1B	DNAL1	Q4LDG9	862
MAP1B	FXR2	P51116	824
MAP1B	ATG16L1	Q676U5	785
MAP1B	ATG7	O95352	784
MAP1B	MAP1LC3C	Q9BXW4	783

IntAct

216 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
ATXN2	PABPC1	psi-mi:“MI:0915”(physical association)	0.820
MAP1LC3B	ATG7	psi-mi:“MI:0914”(association)	0.740
PDCD6	SEC31A	psi-mi:“MI:0914”(association)	0.740
STK4	MAP1B	psi-mi:“MI:0914”(association)	0.730
MAP1LC3B	MAP1B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GABARAPL2	IPO5	psi-mi:“MI:0914”(association)	0.690
MAP1LC3B	OFD1	psi-mi:“MI:0914”(association)	0.660
STK4	STRN	psi-mi:“MI:0914”(association)	0.610
HTR6	MAP1B	psi-mi:“MI:0915”(physical association)	0.580
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
MLF1	HAX1	psi-mi:“MI:0914”(association)	0.560
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
HSPB6	BAG3	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530

BioGRID (626): MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1B (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ3, A4IG66, A4IJ20, A6PVY3, A8NJ91, A8WTH5, B1WC88, B4R3W7, C1BY38, C3KHG1, O01323, O97172, P0C8Y2, P0DKX4, P14873, P15205, P42167, P46821, Q02225, Q15053, Q16EE5, Q28HF6, Q28I13, Q2KI30, Q2TBG9, Q3ZC78, Q4KMI4, Q5F3A1, Q5R431, Q5R4Q3, Q5R7A0, Q5R891, Q5ZML6, Q60665, Q6DFJ8, Q6P5Q4, Q6PFM4, Q7TQ95, Q8BG50, Q8BPM6

Diamond homologs: A6QQ70, P0C5W1, P14400, P14401, P14873, P15205, P34926, P46821, P78559, Q66K74, Q8C052, Q9QYR6, Q9W596

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
DAPK1	up-regulates	MAP1B	binding
GSK3B	“down-regulates activity”	MAP1B	phosphorylation
MAP1B	“up-regulates quantity by stabilization”	Microtubule_polimerization	binding
CUL3	“down-regulates quantity”	MAP1B	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 228 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
Selective autophagy	6	9.8×	5e-03
Autophagy	10	8.7×	8e-05
Macroautophagy	12	8.1×	2e-05
Signaling by Interleukins	11	4.2×	9e-03
Diseases of signal transduction by growth factor receptors and second messengers	12	4.0×	7e-03
Infectious disease	20	2.9×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
hepatocyte apoptotic process	5	24.8×	4e-04
integrated stress response signaling	5	16.6×	2e-03
mitophagy	9	13.5×	1e-05
autophagosome assembly	12	12.7×	3e-07
autophagosome maturation	7	11.6×	5e-04
mRNA stabilization	6	10.4×	4e-03
protein phosphorylation	15	4.8×	3e-04
protein transport	18	3.7×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	15
Uncertain significance	413
Likely benign	142
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1312081	NM_005909.5(MAP1B):c.3879_3882del (p.Val1294fs)	Pathogenic
1527914	NM_005909.5(MAP1B):c.4198A>G (p.Ser1400Gly)	Pathogenic
2574245	NM_005909.5(MAP1B):c.895C>T (p.Arg299Ter)	Pathogenic
2603792	NM_005909.5(MAP1B):c.1988del (p.Lys663fs)	Pathogenic
2771492	NM_005909.5(MAP1B):c.2340del (p.Lys781_Ile782insTer)	Pathogenic
2921146	NM_005909.5(MAP1B):c.6449_6452del (p.Val2150fs)	Pathogenic
3024282	NM_005909.5(MAP1B):c.881del (p.Phe294fs)	Pathogenic
3068466	NM_005909.5(MAP1B):c.3794C>A (p.Ser1265Ter)	Pathogenic
3122718	NM_005909.5(MAP1B):c.6068_6069del (p.Tyr2023fs)	Pathogenic
3254681	NM_005909.5(MAP1B):c.3740C>A (p.Ser1247Ter)	Pathogenic
3365311	NM_005909.5(MAP1B):c.4321del (p.Gln1441fs)	Pathogenic
3572902	NM_005909.5(MAP1B):c.2079_2082del (p.Lys694fs)	Pathogenic
3772391	NM_005909.5(MAP1B):c.6418C>T (p.Arg2140Ter)	Pathogenic
4526403	NM_005909.5(MAP1B):c.6126C>A (p.Tyr2042Ter)	Pathogenic
4531999	NM_005909.5(MAP1B):c.4778_4779insAG (p.Val1595fs)	Pathogenic
638688	NM_005909.5(MAP1B):c.5368C>T (p.Arg1790Ter)	Pathogenic
930211	NM_005909.5(MAP1B):c.2035G>T (p.Glu679Ter)	Pathogenic
986081	NM_005909.5(MAP1B):c.6106dup (p.Asp2036fs)	Pathogenic
1320111	NM_005909.5(MAP1B):c.6715del (p.Asp2238_Leu2239insTer)	Likely pathogenic
1320233	NM_005909.5(MAP1B):c.6733del (p.Thr2245fs)	Likely pathogenic
1341820	NM_005909.5(MAP1B):c.6421C>T (p.Gln2141Ter)	Likely pathogenic
1677307	NM_005909.5(MAP1B):c.1002del (p.Glu334fs)	Likely pathogenic
1722941	NM_005909.5(MAP1B):c.4967A>C (p.Gln1656Pro)	Likely pathogenic
1878324	NM_005909.5(MAP1B):c.3362dup (p.Ser1122fs)	Likely pathogenic
2635122	NM_005909.5(MAP1B):c.2251A>T (p.Lys751Ter)	Likely pathogenic
2664025	NM_005909.5(MAP1B):c.260_261del (p.Ser87fs)	Likely pathogenic
3027255	NM_005909.5(MAP1B):c.4452_4456del (p.Met1484fs)	Likely pathogenic
3235069	NM_005909.5(MAP1B):c.3538_3539del (p.Val1180fs)	Likely pathogenic
3338097	NM_005909.5(MAP1B):c.7191del (p.Ser2398fs)	Likely pathogenic
3346743	NM_005909.5(MAP1B):c.1456C>T (p.Arg486Ter)	Likely pathogenic

SpliceAI

1618 predictions. Top by Δscore:

Variant	Effect	Δscore
5:72107711:GCTCG:G	donor_gain	1.0000
5:72107712:CTCG:C	donor_gain	1.0000
5:72107713:TCG:T	donor_gain	1.0000
5:72107713:TCGGT:T	donor_loss	1.0000
5:72107714:CG:C	donor_gain	1.0000
5:72107714:CGGTA:C	donor_loss	1.0000
5:72107715:GG:G	donor_gain	1.0000
5:72107716:G:GG	donor_gain	1.0000
5:72107716:GT:G	donor_loss	1.0000
5:72107717:T:A	donor_loss	1.0000
5:72115692:CCCTA:C	acceptor_loss	1.0000
5:72115693:CCTA:C	acceptor_loss	1.0000
5:72115694:CTA:C	acceptor_loss	1.0000
5:72115695:TAGG:T	acceptor_loss	1.0000
5:72115697:G:T	acceptor_loss	1.0000
5:72115795:CCCAG:C	donor_loss	1.0000
5:72115796:CCAG:C	donor_loss	1.0000
5:72115797:CAG:C	donor_loss	1.0000
5:72115798:AGG:A	donor_loss	1.0000
5:72115799:GGTGA:G	donor_loss	1.0000
5:72115800:G:GA	donor_loss	1.0000
5:72115801:T:G	donor_loss	1.0000
5:72183726:T:TA	acceptor_gain	1.0000
5:72183732:T:A	acceptor_gain	1.0000
5:72183734:T:TA	acceptor_gain	1.0000
5:72183739:GCA:G	acceptor_loss	1.0000
5:72183741:A:AG	acceptor_gain	1.0000
5:72183741:A:C	acceptor_loss	1.0000
5:72183742:G:GG	acceptor_gain	1.0000
5:72183742:G:GT	acceptor_loss	1.0000

AlphaMissense

16188 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:72107650:T:C	L40P	1.000
5:72115709:T:A	W66R	1.000
5:72115709:T:C	W66R	1.000
5:72115749:T:A	L79H	1.000
5:72115749:T:C	L79P	1.000
5:72115755:T:C	L81P	1.000
5:72115758:T:C	F82S	1.000
5:72183755:T:C	L100P	1.000
5:72183788:T:A	V111D	1.000
5:72183791:T:C	L112P	1.000
5:72186651:T:C	L136P	1.000
5:72186654:T:C	L137P	1.000
5:72193879:T:C	L175P	1.000
5:72193912:T:C	L186S	1.000
5:72193941:T:A	W196R	1.000
5:72193941:T:C	W196R	1.000
5:72193972:T:C	L206P	1.000
5:72193980:T:C	F209L	1.000
5:72193981:T:C	F209S	1.000
5:72193982:C:A	F209L	1.000
5:72193982:C:G	F209L	1.000
5:72193984:T:A	I210N	1.000
5:72194040:T:C	F229L	1.000
5:72194041:T:C	F229S	1.000
5:72194042:T:A	F229L	1.000
5:72194042:T:G	F229L	1.000
5:72194115:T:C	F254L	1.000
5:72194117:T:A	F254L	1.000
5:72194117:T:G	F254L	1.000
5:72194119:T:C	L255P	1.000

dbSNP variants (sampled 300 via entrez): RS1000032092 (5:72135788 A>G), RS1000122436 (5:72153293 G>A), RS1000143270 (5:72143272 T>A,C), RS1000176781 (5:72129035 C>A,G), RS1000198663 (5:72150153 A>G), RS1000280680 (5:72195453 G>A,T), RS1000319416 (5:72180860 C>G), RS1000361050 (5:72108299 T>A,C), RS1000371160 (5:72149424 A>G), RS1000411362 (5:72111998 A>G), RS1000423137 (5:72156097 C>T), RS1000478714 (5:72195494 TAAGAAGGAAGAG>T), RS1000486440 (5:72111733 A>T), RS1000515018 (5:72143639 A>G), RS1000531182 (5:72148583 A>G)

Disease associations

OMIM: gene MIM:157129 | disease phenotypes: MIM:618918, MIM:619808, MIM:612881, MIM:300049

GenCC curated gene-disease

Disease	Classification	Inheritance
periventricular nodular heterotopia 9	Strong	Autosomal dominant
periventricular nodular heterotopia	Strong	Autosomal dominant
hearing loss, autosomal dominant 83	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
periventricular nodular heterotopia	Strong	AD

Mondo (8): periventricular nodular heterotopia 9 (MONDO:0030061), hearing loss, autosomal dominant 83 (MONDO:0030723), chromosome 5Q14.3 deletion syndrome, distal (MONDO:0013031), periventricular nodular heterotopia (MONDO:0020341), pyloric stenosis (MONDO:0001561), attention deficit-hyperactivity disorder (MONDO:0007743), autism spectrum disorder (MONDO:0005258), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): Nodular neuronal heterotopia (Orphanet:2149), Periventricular nodular heterotopia (Orphanet:98892), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000212	Gingival overgrowth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000358	Posteriorly rotated ears
HP:0000664	Synophrys
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000954	Single transverse palmar crease
HP:0000963	Thin skin
HP:0001007	Hirsutism
HP:0001182	Tapered finger
HP:0001212	Prominent fingertip pads
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001382	Joint hypermobility
HP:0001643	Patent ductus arteriosus
HP:0001654	Abnormal heart valve morphology
HP:0001659	Aortic regurgitation
HP:0001761	Pes cavus
HP:0001892	Abnormal bleeding
HP:0002020	Gastroesophageal reflux
HP:0002021	Pyloric stenosis
HP:0002079	Hypoplasia of the corpus callosum
HP:0002126	Polymicrogyria
HP:0002136	Broad-based gait
HP:0002282	Gray matter heterotopia
HP:0002442	Dyscalculia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000246_20	Attention deficit hyperactivity disorder	2.000000e-06
GCST006281_7	Coronary artery disease in type 1 diabetes	1.000000e-09
GCST010002_30	Refractive error	1.000000e-12

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D017219	Gastric Outlet Obstruction	C06.405.748.340
D065886	Neurodevelopmental Disorders	F03.625
D054091	Periventricular Nodular Heterotopia	C10.500.507.450.750; C16.131.666.507.450.750
D011707	Pyloric Stenosis	C06.405.748.340.690
C567876	Heterotopia, Periventricular, Associated With Chromosome 5q Deletion (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3217382 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.00	Kd	10.01	nM	CHEMBL5653589
8.00	ED50	10.01	nM	CHEMBL5653589
7.61	Kd	24.38	nM	CHEMBL3752910
7.61	ED50	24.38	nM	CHEMBL3752910
6.68	Kd	210	nM	CHEMBL3221869

PubChem BioAssay actives

2 with measured affinity, of 12 total; 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148683: Binding affinity to human MAP1B incubated for 45 mins by Kinobead based pull down assay	kd	0.0100	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148683: Binding affinity to human MAP1B incubated for 45 mins by Kinobead based pull down assay	kd	0.0244	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	4
Estradiol	affects cotreatment, increases expression, decreases expression	4
Valproic Acid	affects expression, increases expression	4
methylmercuric chloride	affects cotreatment, increases expression	3
bisphenol A	affects expression, increases expression	3
Tetrachlorodibenzodioxin	affects expression, increases expression	3
Cyclosporine	increases expression	3
methylselenic acid	affects expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Resveratrol	affects cotreatment, decreases expression	2
Acetaminophen	increases expression	2
Cadmium	increases expression	2
Cannabidiol	increases expression	2
Doxorubicin	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
geldanamycin	increases expression	1
propionaldehyde	increases expression	1
lead acetate	increases expression	1
tetrahydropalmatine	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 6 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3223888	Binding	Binding affinity to human MAP1B (582 to 705) expressed in T7 phage after 1 hr by ELISA	The anti-tumor antibiotic PD 113,271 binds to microtubule-associated protein 1B (MAP1B) — Medchemcomm
CHEMBL3630324	Functional	Decrease in MAP1B expression in human U251MG cells at 5 uM for 1 hr by mass spectrometry relative to control	Hirsutinolide Series Inhibit Stat3 Activity, Alter GCN1, MAP1B, Hsp105, G6PD, Vimentin, TrxR1, and Importin α-2 Expression, and Induce Antitumor Effects against Human Glioma. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00556283	PHASE4	COMPLETED	RCT: STARR vs Biofeedback
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00181571	PHASE4	COMPLETED	A Double-Blind Comparison of Concerta and Placebo in Adults With Attention Deficit Hyperactivity Disorder
NCT00181675	PHASE4	COMPLETED	A Double-Blind Comparison of Galantamine HBr and Placebo in Adults With Attention Deficit Hyperactivity Disorder
NCT00181714	PHASE4	COMPLETED	Prevention of Cigarette Smoking in Attention Deficit Hyperactivity Disorder (ADHD) Youth With Concerta
NCT00181948	PHASE4	COMPLETED	Strattera Treatment in Children With ADHD Who Have Poor Response to Stimulant Therapy
NCT00181987	PHASE4	COMPLETED	Concerta in the Treatment of ADHD in Youth and Adults With Bipolar Disorder
NCT00190736	PHASE4	COMPLETED	Efficacy and Safety of Once-Daily Atomoxetine Hydrochloride in Adults With ADHD Over an Extended Period of Time (6 Months)
NCT00190775	PHASE4	COMPLETED	A Randomized, Double-Blind Comparison of Placebo and Atomoxetine Hydrochloride Given Once a Day in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)
NCT00190879	PHASE4	COMPLETED	Placebo-Controlled Study of Atomoxetine Hydrochloride in the Treatment of Adults With ADHD and Comorbid Social Anxiety Disorder
NCT00190957	PHASE4	COMPLETED	Atomoxetine Treatment of Adults With ADHD and Comorbid Alcohol Abuse
NCT00191035	PHASE4	COMPLETED	Maintenance of Benefit With Atomoxetine Hydrochloride in Adolescents With ADHD
NCT00191048	PHASE4	COMPLETED	Treatment With Atomoxetine Hydrochloride in Children and Adolescents With ADHD
NCT00191633	PHASE4	COMPLETED	Study of Atomoxetine in Children With ADHD to Assess Symptomatic and Functional Outcomes
NCT00191906	PHASE4	COMPLETED	Comparison of Atomoxetine and Placebo in Children With Attention-Deficit/Hyperactivity Disorder (ADHD) and/or Reading Disorder (RD)
NCT00216918	PHASE4	COMPLETED	Neuropsychological Functioning in Children With Attention-Deficit/Hyperactivity Disorder.
NCT00221962	PHASE4	COMPLETED	Study of Aripiprazole (Abilify) in Children With ADHD (Attention Deficit Hyperactivity Disorder)
NCT00223561	PHASE4	COMPLETED	Methylphenidate and Driving Ability in Adult Patients With Attention-Deficit Hyperactivity Disorder
NCT00299234	PHASE4	TERMINATED	Atomoxetine for Children With Acquired Attentional Disorders Following Completion of Chemotherapy for ALL
NCT00302406	PHASE4	COMPLETED	Naturalistic Substitution of Concerta in Adult Subject With ADHD Receiving Immediate Release Methylphenidate
NCT00305370	PHASE4	COMPLETED	Aripiprazole Associated With Methylphenidate in Children and Adolescents With Bipolar Disorder and ADHD
NCT00381758	PHASE4	COMPLETED	The COMACS Study: A Comparison of Methylphenidates in an Analog Classroom Setting
NCT00406354	PHASE4	COMPLETED	Comparison of Atomoxetine Versus Placebo in Children and Adolescents With ADHD and Comorbid ODD in Germany
NCT00434213	PHASE4	COMPLETED	Characterization of Dermal Reactions in Pediatric Patients With ADHD Using DAYTRANA
NCT00468143	PHASE4	COMPLETED	A Within-Subject Cross-Over Comparison Between Immediate Release and Extended Release Adderall
NCT00471354	PHASE4	COMPLETED	A Study for Patients With Attention-Deficit/Hyperactivity Disorder Treated With Atomoxetine
NCT00483106	PHASE4	COMPLETED	Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)
NCT00485849	PHASE4	COMPLETED	A Study of Atomoxetine for Attention Deficit and Hyperactive/Impulsive Behaviour Problems in Children With ASD
NCT00485875	PHASE4	COMPLETED	Safety and Efficacy of Switching From a Stimulant Medication to Atomoxetine in Children and Adolescents With ADHD
NCT00486122	PHASE4	COMPLETED	Evaluation of Continuous Symptom Treatment of ADHD
NCT00500071	PHASE4	COMPLETED	Dose-Optimization Study Evaluating the Efficacy, Safety and Tolerability of Vyvanse (Lisdexamfetamine Dimesylate) in Children Aged 6-12 Diagnosed With ADHD
NCT00506727	PHASE4	COMPLETED	Analog Classroom Study Comparison of ADDERALL XR With STRATTERA in Children Aged 6-12 With ADHD
NCT00510276	PHASE4	COMPLETED	Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) With Atomoxetine in Young Adults and Its Effects on Functional Outcomes
NCT00517504	PHASE4	COMPLETED	Methylphenidate Study in Young Children With Developmental Disorders
NCT00517647	PHASE4	COMPLETED	Atomoxetine Pilot Study in Preschool Children With ADHD
NCT00518232	PHASE4	COMPLETED	A Study to Determine Effective and Tolerable Titration Scheme for OROS-Methylphenidate in Children With Attention-deficit Hyperactivity Disorder
NCT00530257	PHASE4	COMPLETED	Study of the Effects of Osmotic-Release Oral System (OROS) Methylphenidate (Concerta) on Attention and Memory
NCT00536419	PHASE4	UNKNOWN	Impact of Attention Deficit/Hyperactivity Disorder and Substance Use Disorder on Motorcycle Traffic Accidents
NCT00546910	PHASE4	COMPLETED	Comparison of Atomoxetine Versus Placebo in Children With Attention-Deficit/Hyperactivity Disorder (ADHD)
NCT00552266	PHASE4	UNKNOWN	Methylphenidate in ADHD With Trichotillomania