MAP6

Summary

MAP6 (microtubule associated protein 6, HGNC:6868) is a protein-coding gene on chromosome 11q13.5, encoding Microtubule-associated protein 6 (Q96JE9). Involved in microtubule stabilization in many cell types, including neuronal cells.

This gene encodes a microtubule-associated protein. The encoded protein is a calmodulin-binding and calmodulin-regulated protein that is involved in microtubule stabilization. Two transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 4135 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_033063

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6868
Approved symbol	MAP6
Name	microtubule associated protein 6
Location	11q13.5
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1878, STOP, FLJ41346, MAP6-N
Ensembl gene	ENSG00000171533
Ensembl biotype	protein_coding
OMIM	601783
Entrez	4135

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000304771, ENST00000434603, ENST00000526689, ENST00000526740, ENST00000950404, ENST00000950405

RefSeq mRNA: 2 — MANE Select: NM_033063 NM_033063, NM_207577

CCDS: CCDS31641, CCDS44686

Canonical transcript exons

ENST00000304771 — 4 exons

Exon	Start	End
ENSE00001153181	75605808	75606004
ENSE00002140904	75586918	75588184
ENSE00002149541	75667465	75669038
ENSE00003560820	75608109	75608322

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 97.93.

FANTOM5 (CAGE): breadth broad, TPM avg 6.8850 / max 151.7130, expressed in 771 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121369	2.8821	620
121371	1.9294	292
121374	0.5276	186
121375	0.4664	166
121373	0.4259	161
121372	0.3616	153
121368	0.1956	90
121366	0.0605	11
121370	0.0359	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.93	gold quality
right frontal lobe	UBERON:0002810	96.94	gold quality
pituitary gland	UBERON:0000007	96.65	gold quality
bronchial epithelial cell	CL:0002328	96.51	gold quality
nucleus accumbens	UBERON:0001882	96.51	gold quality
ganglionic eminence	UBERON:0004023	96.46	gold quality
right uterine tube	UBERON:0001302	96.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.31	gold quality
adenohypophysis	UBERON:0002196	96.22	gold quality
hypothalamus	UBERON:0001898	96.19	gold quality
caudate nucleus	UBERON:0001873	96.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.13	gold quality
bronchus	UBERON:0002185	96.06	gold quality
anterior cingulate cortex	UBERON:0009835	95.98	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.85	gold quality
amygdala	UBERON:0001876	95.78	gold quality
putamen	UBERON:0001874	95.76	gold quality
prefrontal cortex	UBERON:0000451	95.73	gold quality
frontal cortex	UBERON:0001870	95.62	gold quality
frontal lobe	UBERON:0016525	95.62	gold quality
neocortex	UBERON:0001950	95.61	gold quality
forebrain	UBERON:0001890	95.38	gold quality
cerebral cortex	UBERON:0000956	95.30	gold quality
brain	UBERON:0000955	94.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.90	gold quality
temporal lobe	UBERON:0001871	94.59	gold quality
Ammon’s horn	UBERON:0001954	94.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.22	gold quality
lateral globus pallidus	UBERON:0002476	93.96	gold quality
upper arm skin	UBERON:0004263	93.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	34.52
E-HCAD-5	yes	8.58
E-ANND-3	yes	8.54
E-GEOD-124858	no	30.75
E-GEOD-83139	no	3.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting MAP6, 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-205-5P	99.81	70.05	1557
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-6736-3P	96.98	65.22	1342

Literature-anchored findings (GeneRIF, showing 6)

• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• MAP6 might serve as a temperature sensor adapting its conformation according to the temperature to maintain the cellular microtubule network in organisms exposed to temperature decrease. (PMID:22904321)
• Structural basis for the association of MAP6 protein with microtubules and its regulation by calmodulin. (PMID:23831686)
• These data show that TMEM106B/MAP6 interaction is crucial for controlling dendritic trafficking of lysosomes, presumably by acting as a molecular brake for retrograde transport. (PMID:24357581)
• the concentration of STOP/MAP6 protein was significantly reduced in the plasma of autistic subjects than that in healthy controls. (PMID:27541346)
• SPOP Mutations as a Predictive Biomarker for Androgen Receptor Axis-Targeted Therapy in De Novo Metastatic Castration-Sensitive Prostate Cancer. (PMID:36088616)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	map6b	ENSDARG00000074073
danio_rerio	map6a	ENSDARG00000074521
mus_musculus	Map6	ENSMUSG00000055407
rattus_norvegicus	Map6	ENSRNOG00000027204

Paralogs (1): MAP6D1 (ENSG00000180834)

Protein

Protein identifiers

Microtubule-associated protein 6 — Q96JE9 (reviewed: Q96JE9)

Alternative names: Stable tubule-only polypeptide

All UniProt accessions (1): Q96JE9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in microtubule stabilization in many cell types, including neuronal cells. Specifically has microtubule cold stabilizing activity. Involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking via its interaction with TMEM106B. Regulates KIF5A-mediated axonal cargo transport. Regulates axonal growth during neuron polarization.

Subunit / interactions. Interacts with calmodulin (via C-terminus); the interaction is dependent on Ca(2+). Interacts (via C-terminus) with TMEM106B (via N-terminus). Interacts with ZDHHC17 (via ANK repeats). Interacts with ZDHHC13 (via ANK repeats).

Subcellular location. Cytoplasm. Cytoskeleton. Golgi apparatus. Cell projection. Axon. Dendrite. Cytoplasmic vesicle. Secretory vesicle membrane.

Tissue specificity. Expressed in brain (at protein level). Expressed in spinal cord. Isoform 2 expression is up-regulated in the prefrontal cortex (Brodmann’s area 46) of patients with schizophrenia (postmortem brain study).

Post-translational modifications. Palmitoylated. Probably depalmitoylated by ABHD17A, ABHD17B and ABHD17C. During neuronal polarization, palmitoylation and depalmitoylation cycles regulate MAP6 shuttling between secretory vesicles and microtubules, and its polarized distribution in the axon.

Similarity. Belongs to the STOP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96JE9-1	1, N-STOP, Neuronal-STOP	yes
Q96JE9-2	2, E-STOP, Early-STOP
Q96JE9-3	3

RefSeq proteins (2): NP_149052, NP_997460 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007882	MAP6	Family

UniProt features (34 total): region of interest 12, compositionally biased region 10, modified residue 4, lipid moiety-binding region 3, splice variant 2, chain 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JE9-F1	48.50	0.01

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 (7): 102, 143, 187, 812, 5, 10, 11

Mutagenesis-validated functional residues (1):

Position	Phenotype
71	inhibits interaction with zdhhc13 and zdhhc17.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 199 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_DENDRITE_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, GOBP_NEUROGENESIS, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, AAAYRNCTG_UNKNOWN, chr11q13

GO Biological Process (6): microtubule cytoskeleton organization (GO:0000226), cytoskeleton-dependent intracellular transport (GO:0030705), lysosome localization (GO:0032418), dendrite morphogenesis (GO:0048813), positive regulation of axonogenesis (GO:0050772), regulation of microtubule cytoskeleton organization (GO:0070507)

GO Molecular Function (3): calmodulin binding (GO:0005516), microtubule binding (GO:0008017), protein binding (GO:0005515)

GO Cellular Component (13): Golgi-associated vesicle (GO:0005798), cis-Golgi network (GO:0005801), microtubule (GO:0005874), axon (GO:0030424), dendrite (GO:0030425), transport vesicle membrane (GO:0030658), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
intracellular membrane-bounded organelle	2
neuron projection	2
cytoskeleton organization	1
microtubule-based process	1
intracellular transport	1
vacuolar localization	1
dendrite development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
microtubule cytoskeleton organization	1
regulation of microtubule-based process	1
regulation of cytoskeleton organization	1
protein binding	1
tubulin binding	1
binding	1
cytoplasmic vesicle	1
Golgi apparatus	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
dendritic tree	1
transport vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membraneless organelle	1
intracellular vesicle	1

Protein interactions and networks

STRING

950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP6	TMEM106B	Q9NUM4	784
MAP6	CALML6	Q8TD86	698
MAP6	CALML4	Q96GE6	698
MAP6	CALML5	Q9NZT1	698
MAP6	CALML3	P27482	697
MAP6	CALM1	P02593	695
MAP6	PRUNE2	Q8WUY3	558
MAP6	ADNP	Q9H2P0	446
MAP6	PTPN5	P54829	413
MAP6	ADNP2	Q6IQ32	395
MAP6	GTF3C1	Q12789	387
MAP6	DISC1	Q9NRI5	372
MAP6	TBCEL	Q5QJ74	369
MAP6	COQ7	Q99807	354
MAP6	ERGIC1	Q969X5	349

IntAct

19 interactions, top by confidence:

A	B	Type	Score
PB2		psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ANK2	IGKV2-40	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
RIMS1	PSMD12	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
MAPT	PITPNM1	psi-mi:“MI:2364”(proximity)	0.270
MAPT	DCTN6	psi-mi:“MI:2364”(proximity)	0.270
MAPT		psi-mi:“MI:2364”(proximity)	0.270

BioGRID (17): MAP6 (Affinity Capture-MS), MAP6 (Affinity Capture-MS), MAP6 (Two-hybrid), MAP6 (Affinity Capture-Western), MAP6 (Affinity Capture-MS), MAP6 (Affinity Capture-MS), MAP6 (Proximity Label-MS), MAP6 (Affinity Capture-MS), DDX1 (Cross-Linking-MS (XL-MS)), ENO1 (Cross-Linking-MS (XL-MS)), MAP6 (Affinity Capture-MS), MAP6 (Affinity Capture-MS), MAP6 (Affinity Capture-MS), RALGAPA2 (Cross-Linking-MS (XL-MS)), MAP6 (Two-hybrid)

ESM2 similar proteins: A0A1L8HTT5, A0A8I5ZM56, A2AJI0, B0KYV5, B0S4Q5, C0SPG1, D3ZUI5, E1C2Q8, F1LR10, K7SGN7, O70240, O73737, O75128, O88566, P34926, P51826, Q0P591, Q13625, Q14BB9, Q15554, Q3KQU3, Q5PQN4, Q5PR69, Q5RC32, Q5ZJJ1, Q5ZMW6, Q63560, Q69Z61, Q6IQ19, Q6NV74, Q6ZU35, Q7T3T9, Q7T3U0, Q7TSJ2, Q80XA6, Q86XL3, Q8CG79, Q8N7J2, Q8N9B5, Q8NFH8

Diamond homologs: B0S4Q5, O73737, Q0P591, Q14BB9, Q63560, Q7TSJ2, Q96JE9, Q9H9H5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1369 predictions. Top by Δscore:

Variant	Effect	Δscore
11:75588185:C:CC	acceptor_gain	1.0000
11:75588185:C:CG	acceptor_loss	1.0000
11:75588186:T:C	acceptor_loss	1.0000
11:75605806:A:AC	donor_gain	1.0000
11:75605807:C:CC	donor_gain	1.0000
11:75605807:CT:C	donor_gain	1.0000
11:75605819:AG:A	donor_gain	1.0000
11:75605820:G:C	donor_gain	1.0000
11:75608103:TCTCA:T	donor_loss	1.0000
11:75608104:CTCAC:C	donor_loss	1.0000
11:75608105:TCACC:T	donor_loss	1.0000
11:75608106:CACCT:C	donor_loss	1.0000
11:75608107:ACC:A	donor_loss	1.0000
11:75608108:C:CT	donor_loss	1.0000
11:75588180:GGCTC:G	acceptor_gain	0.9900
11:75588182:CTC:C	acceptor_gain	0.9900
11:75588183:TC:T	acceptor_gain	0.9900
11:75588184:CC:C	acceptor_gain	0.9900
11:75608318:CATTC:C	acceptor_gain	0.9900
11:75608320:TTC:T	acceptor_gain	0.9900
11:75608321:TC:T	acceptor_gain	0.9900
11:75608321:TCCT:T	acceptor_loss	0.9900
11:75608322:CC:C	acceptor_gain	0.9900
11:75608322:CCTGT:C	acceptor_loss	0.9900
11:75608323:C:CC	acceptor_gain	0.9900
11:75608323:CTGTT:C	acceptor_loss	0.9900
11:75667459:TCTCA:T	donor_loss	0.9900
11:75667460:CTCAC:C	donor_loss	0.9900
11:75667461:TCA:T	donor_loss	0.9900
11:75667462:CA:C	donor_loss	0.9900

AlphaMissense

5275 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:75668322:C:A	W16C	1.000
11:75668322:C:G	W16C	1.000
11:75668324:A:G	W16R	1.000
11:75668324:A:T	W16R	1.000
11:75668325:G:C	F15L	1.000
11:75668325:G:T	F15L	1.000
11:75668326:A:G	F15S	1.000
11:75668327:A:G	F15L	1.000
11:75668337:G:C	C11W	1.000
11:75668338:C:T	C11Y	1.000
11:75668339:A:G	C11R	1.000
11:75668341:C:T	C10Y	1.000
11:75668342:A:G	C10R	1.000
11:75668347:C:A	R8M	1.000
11:75668357:A:G	C5R	1.000
11:75668361:C:A	W3C	1.000
11:75668361:C:G	W3C	1.000
11:75668363:A:G	W3R	1.000
11:75668363:A:T	W3R	1.000
11:75667851:C:A	W173C	0.999
11:75667851:C:G	W173C	0.999
11:75667853:A:G	W173R	0.999
11:75667853:A:T	W173R	0.999
11:75667881:C:A	W163C	0.999
11:75667881:C:G	W163C	0.999
11:75667883:A:G	W163R	0.999
11:75667883:A:T	W163R	0.999
11:75667890:G:C	F160L	0.999
11:75667890:G:T	F160L	0.999
11:75667891:A:G	F160S	0.999

dbSNP variants (sampled 300 via entrez): RS1000012817 (11:75658991 C>T), RS1000030073 (11:75611408 G>A), RS1000082089 (11:75665418 C>T), RS1000092496 (11:75658067 G>A), RS1000147756 (11:75652820 T>C), RS1000151844 (11:75644790 G>C), RS1000170358 (11:75624649 G>A), RS1000202329 (11:75631581 G>A), RS1000278914 (11:75617846 C>T), RS1000295486 (11:75670319 A>G), RS1000299936 (11:75639164 G>A), RS1000305505 (11:75658380 T>C), RS1000330579 (11:75638869 C>T), RS1000331750 (11:75604849 C>G,T), RS1000346052 (11:75631004 T>A)

Disease associations

OMIM: gene MIM:601783 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	6
trichostatin A	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	3
belinostat	decreases expression, affects cotreatment	2
Panobinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
aflatoxin B2	increases methylation	1
mercuric bromide	affects cotreatment, decreases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	decreases expression	1
thifluzamide	decreases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
picoxystrobin	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Antimycin A	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1

Clinical trials (associated diseases)

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