MAP4

Summary

MAP4 (microtubule associated protein 4, HGNC:6862) is a protein-coding gene on chromosome 3p21.31, encoding Microtubule-associated protein 4 (P27816). Non-neuronal microtubule-associated protein.

The protein encoded by this gene is a major non-neuronal microtubule-associated protein. This protein contains a domain similar to the microtubule-binding domains of neuronal microtubule-associated protein (MAP2) and microtubule-associated protein tau (MAPT/TAU). This protein promotes microtubule assembly, and has been shown to counteract destabilization of interphase microtubule catastrophe promotion. Cyclin B was found to interact with this protein, which targets cell division cycle 2 (CDC2) kinase to microtubules. The phosphorylation of this protein affects microtubule properties and cell cycle progression. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4134 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 259 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001385682

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6862
Approved symbol	MAP4
Name	microtubule associated protein 4
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000047849
Ensembl biotype	protein_coding
OMIM	157132
Entrez	4134

Gene structure

Transcript identifiers

Ensembl transcripts: 121 — 117 protein_coding, 4 retained_intron

ENST00000335271, ENST00000360240, ENST00000383736, ENST00000395734, ENST00000420772, ENST00000423088, ENST00000426837, ENST00000429422, ENST00000434267, ENST00000439356, ENST00000462206, ENST00000468075, ENST00000477765, ENST00000482752, ENST00000497735, ENST00000633710, ENST00000683076, ENST00000876259, ENST00000876260, ENST00000876261, ENST00000876262, ENST00000876263, ENST00000876264, ENST00000876265, ENST00000876266, ENST00000876267, ENST00000876268, ENST00000876269, ENST00000876270, ENST00000876271, ENST00000876272, ENST00000876273, ENST00000876274, ENST00000876275, ENST00000876276, ENST00000876277, ENST00000876278, ENST00000876279, ENST00000876280, ENST00000876281, ENST00000876282, ENST00000876283, ENST00000876284, ENST00000876285, ENST00000876286, ENST00000876287, ENST00000876288, ENST00000876289, ENST00000876290, ENST00000876291, ENST00000876292, ENST00000876293, ENST00000876294, ENST00000876295, ENST00000876296, ENST00000876297, ENST00000876298, ENST00000876299, ENST00000876300, ENST00000876301, ENST00000876302, ENST00000876303, ENST00000876304, ENST00000876305, ENST00000876306, ENST00000876307, ENST00000876308, ENST00000876309, ENST00000876310, ENST00000876311, ENST00000876312, ENST00000876313, ENST00000876314, ENST00000922512, ENST00000922513, ENST00000922514, ENST00000922515, ENST00000922516, ENST00000922517, ENST00000922518, ENST00000922519, ENST00000922520, ENST00000922521, ENST00000922522, ENST00000922523, ENST00000922524, ENST00000922525, ENST00000972333, ENST00000972334, ENST00000972335, ENST00000972336, ENST00000972337, ENST00000972338, ENST00000972339, ENST00000972340, ENST00000972341, ENST00000972342, ENST00000972343, ENST00000972344, ENST00000972345, ENST00000972346, ENST00000972347, ENST00000972348, ENST00000972349, ENST00000972350, ENST00000972351, ENST00000972352, ENST00000972353, ENST00000972354, ENST00000972355, ENST00000972356, ENST00000972357, ENST00000972358, ENST00000972359, ENST00000972360, ENST00000972361, ENST00000972362, ENST00000972363, ENST00000972364, ENST00000972365, ENST00000972366

RefSeq mRNA: 144 — MANE Select: NM_001385682 NM_001134364, NM_001384675, NM_001384676, NM_001384677, NM_001384678, NM_001384679, NM_001384680, NM_001384681, NM_001384707, NM_001384729, NM_001384730, NM_001384731, NM_001384733, NM_001384734, NM_001384735, NM_001384736, NM_001384737, NM_001384738, NM_001384744, NM_001384745, NM_001384746, NM_001384748, NM_001384751, NM_001384752, NM_001384753, NM_001384754, NM_001384755, NM_001384756, NM_001384757, NM_001384758, NM_001384759, NM_001384760, NM_001384761, NM_001384762, NM_001384774, NM_001384776, NM_001384777, NM_001384778, NM_001384779, NM_001384780, NM_001384781, NM_001384782, NM_001384783, NM_001384784, NM_001384785, NM_001384786, NM_001384787, NM_001384788, NM_001384789, NM_001384790, NM_001384791, NM_001384792, NM_001384793, NM_001384794, NM_001384795, NM_001384796, NM_001384797, NM_001384798, NM_001384800, NM_001384802, NM_001384803, NM_001384804, NM_001384805, NM_001384806, NM_001384807, NM_001384808, NM_001384809, NM_001384810, NM_001384811, NM_001384812, NM_001384813, NM_001384814, NM_001384815, NM_001384816, NM_001384817, NM_001384819, NM_001384820, NM_001384824, NM_001384825, NM_001384826, NM_001384827, NM_001384828, NM_001384831, NM_001384832, NM_001384834, NM_001384835, NM_001384836, NM_001384837, NM_001384838, NM_001384839, NM_001384840, NM_001384841, NM_001384842, NM_001384843, NM_001384844, NM_001384845, NM_001384846, NM_001384847, NM_001384848, NM_001384849, NM_001384850, NM_001384851, NM_001384853, NM_001384856, NM_001384857, NM_001384859, NM_001384861, NM_001384862, NM_001384863, NM_001384864, NM_001384866, NM_001384867, NM_001384868, NM_001384869, NM_001384870, NM_001384871, NM_001384872, NM_001384873, NM_001384874, NM_001384875, NM_001384876, NM_001384877, NM_001384878, NM_001384879, NM_001384892, NM_001384893, NM_001385664, NM_001385665, NM_001385675, NM_001385676, NM_001385677, NM_001385681, NM_001385682, NM_001385684, NM_001385685, NM_001385686, NM_001385687, NM_001385688, NM_001385689, NM_001385690, NM_001385691, NM_001385692, NM_002375, NM_030885

CCDS: CCDS33750, CCDS46818, CCDS46821, CCDS93263

Canonical transcript exons

ENST00000683076 — 21 exons

Exon	Start	End
ENSE00000902985	47867246	47867338
ENSE00001172167	47855248	47855360
ENSE00001172258	47857431	47857512
ENSE00001241639	47977865	47977933
ENSE00001338194	47869214	47869327
ENSE00001338200	47870813	47871105
ENSE00001338202	47875685	47875900
ENSE00001380081	47853163	47853352
ENSE00001434372	47998638	47998879
ENSE00001663893	47915951	47917174
ENSE00001670142	47918719	47918841
ENSE00001723907	47909038	47912421
ENSE00001758869	47928228	47928350
ENSE00001791274	47914817	47914939
ENSE00003512996	47877417	47877523
ENSE00003550764	47921765	47921878
ENSE00003627763	47871227	47871286
ENSE00003657589	47871917	47872100
ENSE00003919697	48016334	48016416
ENSE00003920830	47902950	47903000
ENSE00003921737	47850695	47852938

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 173.4166 / max 1765.4946, expressed in 1824 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42096	155.0655	1824
42095	4.9183	1469
42098	3.3945	1485
42071	3.1938	193
42097	1.8028	979
42092	1.4679	210
42070	0.7679	149
42063	0.7114	339
42069	0.4003	101
42068	0.3439	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.86	gold quality
medial globus pallidus	UBERON:0002477	99.81	gold quality
inferior olivary complex	UBERON:0002127	99.80	gold quality
endothelial cell	CL:0000115	99.75	gold quality
globus pallidus	UBERON:0001875	99.74	gold quality
cranial nerve II	UBERON:0000941	99.67	gold quality
tendon of biceps brachii	UBERON:0008188	99.66	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.65	gold quality
spinal cord	UBERON:0002240	99.60	gold quality
inferior vagus X ganglion	UBERON:0005363	99.59	gold quality
medulla oblongata	UBERON:0001896	99.57	gold quality
subthalamic nucleus	UBERON:0001906	99.56	gold quality
ventral tegmental area	UBERON:0002691	99.56	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.55	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.47	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.46	gold quality
lateral globus pallidus	UBERON:0002476	99.43	gold quality
superior vestibular nucleus	UBERON:0007227	99.41	gold quality
apex of heart	UBERON:0002098	99.39	gold quality
substantia nigra pars compacta	UBERON:0001965	99.31	gold quality
gluteal muscle	UBERON:0002000	99.30	gold quality
midbrain	UBERON:0001891	99.29	gold quality
substantia nigra	UBERON:0002038	99.28	gold quality
hypothalamus	UBERON:0001898	99.24	gold quality
amygdala	UBERON:0001876	99.22	gold quality
olfactory bulb	UBERON:0002264	99.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.14	gold quality
body of tongue	UBERON:0011876	99.10	gold quality
Ammon’s horn	UBERON:0001954	99.08	gold quality
trigeminal ganglion	UBERON:0001675	99.06	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	46.84
E-GEOD-137537	yes	21.27
E-CURD-10	no	451.89
E-CURD-112	no	3.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53, WT1

miRNA regulators (miRDB)

67 targeting MAP4, 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-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-5003-5P	99.61	69.13	1624

Literature-anchored findings (GeneRIF, showing 29)

• Results suggest that structural features of the PJ domain of MAP4 may contribute to the formation of a radial array of microtubules in proliferating cells. (PMID:12079337)
• demonstrate that ectopic MAP4 promotes outgrowth of extended MTs during beta1-integrin-induced cell spreading (PMID:12123579)
• activity of MAP4 is downregulated by reduced free tubulin concentrations (PMID:12890753)
• adenovirus 2 E1B-55K protein blocks p53 as a transcriptional repressor protein of the survivin and the MAP4 promoters (PMID:14527689)
• MAP4 microtubule decoration interferes with beta-adrenergic receptor recycling and that this may be one mechanism for beta-adrenergic receptor downregulation in heart failure. (PMID:15528234)
• Truncation of the projection domain of MAP4 leads to attenuation of microtubule dynamic instability. (PMID:15840946)
• mAP4 interaction with septins modulates microtubule dynamics. (PMID:16093351)
• This first report of a genetic alteration involving MAP4 points to a potentially relevant target gene in diffuse large B-cell lymphoma. (PMID:16804917)
• Data found the ratio of MAP4 to stathmin mRNA was found to be higher in diseased lung tissues compared to normal lung tissues, suggesting this ratio might also be used as a clinically relevant biomarker for NSCLCs. (PMID:18613117)
• Data show that the tau-related protein MAP4 and the microtubule rescue factor CLASP1 are essential for maintaining spindle position and the correct cell-division axis. (PMID:21822276)
• DNAL1 and MAP4 may exert their functions in the HIV life cycle at reverse transcription, prior to nuclear translocation. (PMID:22018492)
• there are two possible mechanisms triggered by MAP4: stabilization of MT networks; DYNLT1 modulation, which is connected with VDAC1, and inhibition of hypoxia-induced mitochondrial permeabilization (PMID:22164227)
• MAP4, which is a binding partner of SEPT2. (PMID:23572511)
• Data show that cAMP/alpha isoform of the catalytic subunit of human PKA (PKAc-alpha) signaling can disrupt microtubule (MT) cytoskeleton by the phosphorylation of microtubule-Associated Protein 4 (MAP4). (PMID:24140250)
• Results demonstrated that MAP4 mutations contribute to the clinical spectrum of centrosomal defects and confirmed the complex role of a centrosomal protein in centrosomal, ciliary, and Golgi regulation associated with severe short stature. (PMID:25323976)
• We demonstrated that the MAP4 (Ser696 and Ser787) phosphorylation increased concomitantly with the p38/MAPK pathway activation by the LPS and TNF-alpha stimulation of HPMECs, which induced MT disassembly followed by hyperpermeability. (PMID:25746230)
• Results show that marker rs218966 in gene PHF14 and rs9836027 in MAP4 significantly associated with hypertension; additionally, rare variants in SNUPN significantly associated with systolic blood pressure. (PMID:26866982)
• an intratumoral injection of MAP4-small interfering RNA (siRNA) remarkably inhibited the growth of the tumors that formed by the MAP4-expressing ESCC cells in nude mice, and a combination of MAP4-siRNA and Bevacizumab significantly enhanced the inhibition effect. Our data suggest that MAP4 is probably a useful prognostic biomarker and a potential therapeutic target for the disease. (PMID:26876215)
• Microtubule-associated protein 4 (MAP4) controls the dynein-dependent transport of BTN3A1 in response to nucleic acid stimulation, thereby identifying MAP4 as an upstream regulator of BTN3A1. Thus, the depletion of either MAP4 or BTN3A1 impairs cytosolic DNA- or RNA-mediated type I IFN responses. (PMID:27911820)
• MAP4 acts as a checkpoint molecule that balances positive and negative hallmarks of T cell activation. (PMID:28209780)
• Expression level of MAP4 mRNA and protein in lung adenocarcinoma tissues were significantly higher than those in noncancerous tissues. MAP4 expression significantly correlated with tumor progression. (PMID:29743960)
• Further experiments revealed that MAP4 regulates microtubule dynamics and promotes epidermal cell migration through Tctex-1. MAP4 and Tctex-1 play important roles in regulating the migration of epidermal cells under hypoxia. (PMID:30091292)
• The strongest bond of MAP4 was found around the intertubulin-dimer interface such that MAP4 coexists on the microtubule with kinesin-1 bound to the intratubulin-dimer interface as well. (PMID:30275105)
• Results suggest that Syk, MAP4, and calpain-1 expression are correlated with each other and these proteins may be involved in early stages of tumour spread. (PMID:30737623)
• study reveals a molecular mechanism by which HPV16E7 perturbs host mitotic progression by interfering Mps1-MAP4 signaling cascade, which results in an extended infection window and may facilitate the persistent HPV16 infection (PMID:31253867)
• Phosphatidylinositol-3-OH kinase signalling is spatially organized at endosomal compartments by microtubule-associated protein 4. (PMID:33139939)
• Effects of three microtubule-associated proteins (MAP2, MAP4, and Tau) on microtubules’ physical properties and neurite morphology. (PMID:37258650)
• MAP4 acts as an oncogene and prognostic marker and affects radioresistance by mediating epithelial-mesenchymal transition in lung adenocarcinoma. (PMID:38341398)
• A p85 isoform switch enhances PI3K activation on endosomes by a MAP4- and PI3P-dependent mechanism. (PMID:38630589)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Microtubule-associated protein 4 — P27816 (reviewed: P27816)

All UniProt accessions (10): A0A0J9YVV8, A0A0J9YW37, A0A804HKE7, B5MEG9, P27816, E7EVA0, F8W9U4, H0Y2V1, H7C456, H7C4C5

UniProt curated annotations — full annotation on UniProt →

Function. Non-neuronal microtubule-associated protein. Promotes microtubule assembly.

Subunit / interactions. Interacts with SEPTIN2; this interaction impedes tubulin-binding. Interacts with TRAF3IP1. Interacts with KNSTRN.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center.

Post-translational modifications. Phosphorylated at serine residues in K-X-G-S motifs by MAP/microtubule affinity-regulating kinase (MARK1 or MARK2), causing detachment from microtubules, and their disassembly. Phosphorylation on Ser-787 negatively regulates MAP4 activity to promote microtubule assembly. Isoform 3 is phosphorylated on Ser-337 and Ser-338.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (7)

UniProt ID	Names	Canonical?
P27816-1	1	yes
P27816-2	2
P27816-3	3
P27816-4	4
P27816-5	5
P27816-6	6
P27816-7	7

RefSeq proteins (144): NP_001127836, NP_001371604, NP_001371605, NP_001371606, NP_001371607, NP_001371608, NP_001371609, NP_001371610, NP_001371636, NP_001371658, NP_001371659, NP_001371660, NP_001371662, NP_001371663, NP_001371664, NP_001371665, NP_001371666, NP_001371667, NP_001371673, NP_001371674, NP_001371675, NP_001371677, NP_001371680, NP_001371681, NP_001371682, NP_001371683, NP_001371684, NP_001371685, NP_001371686, NP_001371687, NP_001371688, NP_001371689, NP_001371690, NP_001371691, NP_001371703, NP_001371705, NP_001371706, NP_001371707, NP_001371708, NP_001371709, NP_001371710, NP_001371711, NP_001371712, NP_001371713, NP_001371714, NP_001371715, NP_001371716, NP_001371717, NP_001371718, NP_001371719, NP_001371720, NP_001371721, NP_001371722, NP_001371723, NP_001371724, NP_001371725, NP_001371726, NP_001371727, NP_001371729, NP_001371731, NP_001371732, NP_001371733, NP_001371734, NP_001371735, NP_001371736, NP_001371737, NP_001371738, NP_001371739, NP_001371740, NP_001371741, NP_001371742, NP_001371743, NP_001371744, NP_001371745, NP_001371746, NP_001371748, NP_001371749, NP_001371753, NP_001371754, NP_001371755, NP_001371756, NP_001371757, NP_001371760, NP_001371761, NP_001371763, NP_001371764, NP_001371765, NP_001371766, NP_001371767, NP_001371768, NP_001371769, NP_001371770, NP_001371771, NP_001371772, NP_001371773, NP_001371774, NP_001371775, NP_001371776, NP_001371777, NP_001371778, NP_001371779, NP_001371780, NP_001371782, NP_001371785, NP_001371786, NP_001371788, NP_001371790, NP_001371791, NP_001371792, NP_001371793, NP_001371795, NP_001371796, NP_001371797, NP_001371798, NP_001371799, NP_001371800, NP_001371801, NP_001371802, NP_001371803, NP_001371804, NP_001371805, NP_001371806, NP_001371807, NP_001371808, NP_001371821, NP_001371822, NP_001372593, NP_001372594, NP_001372604, NP_001372605, NP_001372606, NP_001372610, NP_001372611, NP_001372613, NP_001372614, NP_001372615, NP_001372616, NP_001372617, NP_001372618, NP_001372619, NP_001372620, NP_001372621, NP_002366, NP_112147 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001084	MAP_tubulin-bd_rpt	Repeat
IPR027324	MAP2/MAP4/Tau	Family

Pfam: PF00418

UniProt features (122 total): modified residue 45, repeat 23, splice variant 18, compositionally biased region 14, sequence variant 8, region of interest 5, sequence conflict 3, mutagenesis site 2, cross-link 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P27816-F1	43.03	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.

Post-translational modifications (47): 337, 338, 28, 269, 803, 2, 5, 14, 60, 99, 253, 280, 282, 354, 358, 380, 384, 440, 442, 507 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
696	no change in microtubule binding; no change in microtubule polymerization activity.
787	no change in microtubule binding; reduced microtubule polymerization activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 289 (showing top): GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, CREL_01, AP1_01, WANG_CLIM2_TARGETS_UP, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, PAL_PRMT5_TARGETS_UP, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_SPINDLE_LOCALIZATION, GOBP_NEUROGENESIS, ACTGCAG_MIR173P, CHX10_01, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, GOCC_MICROTUBULE_ORGANIZING_CENTER

GO Biological Process (9): microtubule cytoskeleton organization (GO:0000226), mitotic spindle organization (GO:0007052), neuron projection development (GO:0031175), microtubule polymerization (GO:0046785), microtubule sliding (GO:0051012), establishment of spindle orientation (GO:0051294), cell division (GO:0051301), cilium disassembly (GO:0061523), negative regulation of non-motile cilium assembly (GO:1902856)

GO Molecular Function (6): RNA binding (GO:0003723), structural molecule activity (GO:0005198), microtubule binding (GO:0008017), microtubule stabilizing activity (GO:0140778), protein binding (GO:0005515), tubulin binding (GO:0015631)

GO Cellular Component (15): acrosomal vesicle (GO:0001669), microtubule organizing center (GO:0005815), cytosol (GO:0005829), microtubule (GO:0005874), microtubule associated complex (GO:0005875), plasma membrane (GO:0005886), cilium (GO:0005929), axoneme (GO:0005930), microtubule cytoskeleton (GO:0015630), axon (GO:0030424), ciliary basal body (GO:0036064), neuron projection (GO:0043005), mitotic spindle (GO:0072686), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
microtubule cytoskeleton	3
plasma membrane bounded cell projection	2
cytoskeleton	2
cytoskeleton organization	1
microtubule-based process	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
neuron development	1
plasma membrane bounded cell projection organization	1
microtubule nucleation	1
microtubule polymerization or depolymerization	1
protein polymerization	1
supramolecular fiber organization	1
microtubule-based movement	1
establishment of cell polarity	1
establishment of spindle localization	1
cellular process	1
cilium organization	1
organelle disassembly	1
negative regulation of cilium assembly	1
regulation of non-motile cilium assembly	1
non-motile cilium assembly	1
nucleic acid binding	1
molecular_function	1
tubulin binding	1
protein-containing complex stabilizing activity	1
binding	1
cytoskeletal protein binding	1
secretory granule	1
cytoplasm	1
polymeric cytoskeletal fiber	1
protein-containing complex	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
microtubule	1
ciliary plasm	1

Protein interactions and networks

STRING

1904 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP4	MARK3	P27448	841
MAP4	ANP32A	P39687	772
MAP4	STMN1	P16949	726
MAP4	CDC25C	P30307	635
MAP4	SEPTIN2	Q15019	625
MAP4	CLASP2	O75122	572
MAP4	CLIP1	P30622	555
MAP4	KSR1	Q8IVT5	549
MAP4	SEPTIN11	Q9NVA2	545
MAP4	CDK1	P06493	532
MAP4	MAP1B	P46821	479
MAP4	BUB1B	O60566	453
MAP4	CEP164	Q9UPV0	447
MAP4	RANBP2	P49792	447
MAP4	SEPTIN7	Q16181	444

IntAct

261 interactions, top by confidence:

A	B	Type	Score
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
EPN1	PHGDH	psi-mi:“MI:0914”(association)	0.710
E7	RB1	psi-mi:“MI:0914”(association)	0.700
MAP4	CAPN1	psi-mi:“MI:0915”(physical association)	0.560
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
	AP3D1	psi-mi:“MI:0914”(association)	0.460
MAP4	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	SNTG2	psi-mi:“MI:0407”(direct interaction)	0.440
WHRN	MAP4	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
PDZRN3	MAP4	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
MAP4	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (399): MAP4 (Affinity Capture-MS), MAP4 (Affinity Capture-MS), FLNB (Co-fractionation), LSM3 (Co-fractionation), MAP4 (Co-fractionation), MAP4 (Co-fractionation), MAP4 (Co-fractionation), SERBP1 (Co-fractionation), SLK (Co-fractionation), MAP4 (Affinity Capture-MS), MAP4 (Proximity Label-MS), MAP4 (Biochemical Activity), MAP4 (Affinity Capture-MS), MAP4 (Affinity Capture-MS), MAP4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUW6, A1EGX6, A4FU49, A6NJ88, A6QP92, E9PAV3, E9Q0C6, F1QU13, O94854, P18583, P24587, P27546, P27816, P36225, P43597, P70670, Q08DY0, Q2T9N0, Q32L62, Q4R729, Q4V7A4, Q5H9T9, Q5M7W5, Q5SWP3, Q5XHX6, Q5XPK0, Q659K0, Q68DN1, Q68FX6, Q69ZZ9, Q6AZ54, Q6P6B1, Q6ZRG5, Q70KF4, Q710D7, Q810T2, Q8K4E0, Q8N3K9, Q8TCU4, Q8WWL7

Diamond homologs: O02828, P10636, P10637, P11137, P15146, P19332, P20357, P27546, P27816, P29172, P36225, P57786, Q5M7W5, Q5S6V2, Q5YCV9, Q5YCW0, Q5YCW1, Q6TS35, Q9MYX8

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
TTK	“down-regulates quantity by destabilization”	MAP4	phosphorylation
CDK1	“down-regulates activity”	MAP4	phosphorylation
MAP4	up-regulates	Microtubule_polimerization
CDK1	unknown	MAP4	phosphorylation
CHEK1	“down-regulates quantity by destabilization”	MAP4	phosphorylation
CDK1	down-regulates	MAP4	phosphorylation
MARK1	“down-regulates activity”	MAP4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 188 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
Assembly and cell surface presentation of NMDA receptors	7	13.6×	3e-04
Neurexins and neuroligins	8	12.0×	2e-04
RHOV GTPase cycle	5	10.9×	9e-03
SARS-CoV-1-host interactions	6	8.1×	9e-03
SARS-CoV-2-host interactions	7	6.4×	9e-03
Infectious disease	16	3.0×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	7	24.6×	1e-05
protein localization to synapse	5	23.2×	5e-04
receptor clustering	6	22.7×	9e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	7	21.0×	2e-05
axonogenesis	7	6.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	173
Likely benign	34
Benign	12

Top pathogenic / likely-pathogenic (0)

SpliceAI

5530 predictions. Top by Δscore:

Variant	Effect	Δscore
3:47853156:CACTT:C	donor_loss	1.0000
3:47853157:ACTTA:A	donor_loss	1.0000
3:47853159:TTAC:T	donor_loss	1.0000
3:47853160:TA:T	donor_loss	1.0000
3:47853161:A:AC	donor_gain	1.0000
3:47853161:A:T	donor_loss	1.0000
3:47853162:C:CC	donor_gain	1.0000
3:47853162:CTTGT:C	donor_gain	1.0000
3:47855260:T:TA	donor_gain	1.0000
3:47855358:CAC:C	acceptor_gain	1.0000
3:47855361:C:CC	acceptor_gain	1.0000
3:47855361:C:CG	acceptor_loss	1.0000
3:47855362:T:G	acceptor_loss	1.0000
3:47857430:CCAGG:C	donor_gain	1.0000
3:47870801:C:CA	donor_gain	1.0000
3:47870819:T:TA	donor_gain	1.0000
3:47871103:CAG:C	acceptor_gain	1.0000
3:47871106:C:CC	acceptor_gain	1.0000
3:47871914:CACC:C	donor_loss	1.0000
3:47871915:A:AC	donor_gain	1.0000
3:47871915:AC:A	donor_gain	1.0000
3:47871916:C:CT	donor_gain	1.0000
3:47871916:CC:C	donor_gain	1.0000
3:47871916:CCAG:C	donor_gain	1.0000
3:47872096:ATGGG:A	acceptor_gain	1.0000
3:47872097:TGGG:T	acceptor_gain	1.0000
3:47872098:GGG:G	acceptor_gain	1.0000
3:47872099:GG:G	acceptor_gain	1.0000
3:47872101:C:CC	acceptor_gain	1.0000
3:47877412:CCTA:C	donor_loss	1.0000

AlphaMissense

15003 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:47857505:A:G	I1025T	0.998
3:47998787:A:G	F25S	0.998
3:47857511:A:T	V1023D	0.997
3:47867291:C:A	K1007N	0.997
3:47867291:C:G	K1007N	0.997
3:47998775:A:G	L29P	0.997
3:47998782:C:G	A27P	0.997
3:47855292:A:G	S1073P	0.996
3:47855309:G:T	A1067D	0.996
3:47855317:C:A	K1064N	0.996
3:47855317:C:G	K1064N	0.996
3:47855320:G:C	F1063L	0.996
3:47855320:G:T	F1063L	0.996
3:47855322:A:G	F1063L	0.996
3:47855348:A:T	V1054D	0.996
3:47857460:C:T	G1040E	0.996
3:47857464:A:G	C1039R	0.996
3:47857505:A:C	I1025S	0.996
3:47998786:G:C	F25L	0.996
3:47998786:G:T	F25L	0.996
3:47998788:A:G	F25L	0.996
3:47855299:C:A	K1070N	0.995
3:47855299:C:G	K1070N	0.995
3:47855321:A:G	F1063S	0.995
3:47857440:G:C	H1047D	0.995
3:47867279:C:A	K1011N	0.995
3:47867279:C:G	K1011N	0.995
3:47867284:A:G	S1010P	0.995
3:47867290:A:G	C1008R	0.995
3:47867293:T:C	K1007E	0.995

dbSNP variants (sampled 300 via entrez): RS1000017073 (3:47878823 C>T), RS1000017921 (3:47954886 G>A), RS1000023716 (3:47972201 T>C,G), RS1000044246 (3:47942136 C>G), RS1000069134 (3:48064335 G>A), RS1000087179 (3:47986642 C>T), RS1000120221 (3:48018894 A>G), RS1000126002 (3:48025942 T>C,G), RS1000171801 (3:47945373 A>G), RS1000189448 (3:47992327 G>T), RS1000189494 (3:48020338 T>C), RS1000189886 (3:47880282 G>T), RS1000198000 (3:47935629 T>C), RS1000201135 (3:47872754 C>A,T), RS1000203067 (3:47883349 T>C)

Disease associations

OMIM: gene MIM:157132 | disease phenotypes: MIM:148840

GenCC curated gene-disease

Mondo (1): Kleine-Levin syndrome (MONDO:0007863)

Orphanet (1): Kleine-Levin syndrome (Orphanet:33543)

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST001236_23	Blood pressure	3.000000e-08
GCST004776_14	Systolic blood pressure	2.000000e-06
GCST004777_2	Diastolic blood pressure	9.000000e-07
GCST006231_20	Mean arterial pressure	1.000000e-06
GCST006258_2	Diastolic blood pressure	2.000000e-15
GCST006259_42	Systolic blood pressure	2.000000e-10
GCST007094_1	Diastolic blood pressure	1.000000e-16
GCST007094_202	Diastolic blood pressure	4.000000e-17
GCST007095_30	Systolic blood pressure	5.000000e-07
GCST007096_132	Pulse pressure	3.000000e-06
GCST007098_41	Diastolic blood pressure	5.000000e-06
GCST007099_172	Systolic blood pressure	1.000000e-12
GCST007099_260	Systolic blood pressure	3.000000e-16
GCST007267_254	Systolic blood pressure	3.000000e-16
GCST007929_93	Medication use (calcium channel blockers)	1.000000e-08
GCST008595_30	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-09
GCST010396_163	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-06
GCST011331_2	Body mass index and systole blood pressure (pairwise)	1.000000e-08
GCST90013406_247	Liver enzyme levels (alkaline phosphatase)	1.000000e-12

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0006340	mean arterial pressure
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0007874	gut microbiome measurement
EFO:0004340	body mass index
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D017593	Kleine-Levin Syndrome	C10.886.425.800.200.500; F03.870.400.800.200.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724642 (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: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.14	Kd	7163	nM	CHEMBL5653589
5.14	ED50	7163	nM	CHEMBL5653589
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 8 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	2148696: Binding affinity to human MAP4 incubated for 45 mins by Kinobead based pull down assay	kd	7.1635	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178741: Inhibition of MAP4 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation	5
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Doxorubicin	affects expression, decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
mercuric bromide	affects cotreatment, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Resveratrol	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Cadmium	increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	increases expression, increases abundance	2
Genistein	decreases expression, increases reaction	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	affects sumoylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
decabromobiphenyl ether	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	increases phosphorylation	1
artenimol	affects binding	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation, increases ADP-ribosylation	1
monomethylarsonous acid	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651738	Binding	Binding affinity to human MAP4 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1WM	Abcam HeLa MAP4 KO	Cancer cell line	Female
CVCL_SW79	HAP1 MAP4 (-) 1	Cancer cell line	Male
CVCL_SW80	HAP1 MAP4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02337023	Not specified	COMPLETED	Brain Scintigraphy in Normal Versus Kleine-Levin Syndrome Subjects
NCT03754348	Not specified	COMPLETED	Microglial Activation in Narcolepsy Type 1 and Kleine-Levin Syndrome: Positron Emission Tomography (PET) Study in [18F] DPA-714