MZT2A

Summary

MZT2A (mitotic spindle organizing protein 2A, HGNC:33187) is a protein-coding gene on chromosome 2q21.1, encoding Mitotic-spindle organizing protein 2A (Q6P582). Required for the recruitment and the assembly of the gamma-tubulin ring complex (gTuRC) at the centrosome. It is a selective cancer dependency (DepMap: 20.9% of cell lines).

Located in centrosome; cytosol; and nucleoplasm.

Source: NCBI Gene 653784 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 119 total — 2 pathogenic
• Cancer dependency (DepMap): dependent in 20.9% of screened cell lines
• MANE Select transcript: NM_001085365

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33187
Approved symbol	MZT2A
Name	mitotic spindle organizing protein 2A
Location	2q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MOZART2A
Ensembl gene	ENSG00000173272
Ensembl biotype	protein_coding
OMIM	613449
Entrez	653784

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000309451, ENST00000410036, ENST00000427024, ENST00000445782, ENST00000488586, ENST00000491265, ENST00000886553, ENST00000886554, ENST00000937869, ENST00000937870, ENST00000967877

RefSeq mRNA: 1 — MANE Select: NM_001085365 NM_001085365

CCDS: CCDS42758

Canonical transcript exons

ENST00000309451 — 3 exons

Exon	Start	End
ENSE00002441654	131483960	131484218
ENSE00003640913	131491876	131492024
ENSE00003851193	131492207	131492397

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.0725 / max 381.7539, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30634	58.0725	1825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.92	gold quality
apex of heart	UBERON:0002098	98.48	gold quality
amygdala	UBERON:0001876	98.35	gold quality
heart left ventricle	UBERON:0002084	98.19	gold quality
cardiac ventricle	UBERON:0002082	98.18	gold quality
anterior cingulate cortex	UBERON:0009835	98.10	gold quality
cingulate cortex	UBERON:0003027	98.09	gold quality
lower esophagus mucosa	UBERON:0035834	98.09	gold quality
prefrontal cortex	UBERON:0000451	97.79	gold quality
nucleus accumbens	UBERON:0001882	97.78	gold quality
heart right ventricle	UBERON:0002080	97.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.56	gold quality
endocervix	UBERON:0000458	97.50	gold quality
right frontal lobe	UBERON:0002810	97.49	gold quality
temporal lobe	UBERON:0001871	97.35	gold quality
thymus	UBERON:0002370	97.25	gold quality
neocortex	UBERON:0001950	97.17	gold quality
left ovary	UBERON:0002119	97.17	gold quality
frontal cortex	UBERON:0001870	97.14	gold quality
putamen	UBERON:0001874	97.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.11	gold quality
cervix squamous epithelium	UBERON:0006922	97.10	gold quality
hypothalamus	UBERON:0001898	97.07	gold quality
Ammon’s horn	UBERON:0001954	97.04	gold quality
right uterine tube	UBERON:0001302	97.02	gold quality
substantia nigra pars compacta	UBERON:0001965	97.01	gold quality
cerebral cortex	UBERON:0000956	96.93	gold quality
left uterine tube	UBERON:0001303	96.91	gold quality
caudate nucleus	UBERON:0001873	96.91	gold quality
telencephalon	UBERON:0001893	96.88	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	20.69
E-GEOD-125970	yes	16.74
E-MTAB-10042	yes	7.77
E-CURD-88	yes	7.53
E-MTAB-7606	no	273.46
E-CURD-89	no	55.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting MZT2A, 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-4731-5P	99.89	67.23	2537
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-576-3P	96.14	65.63	773
HSA-MIR-4330	95.44	66.39	993

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Data show that depletion of GCP8 specifically affects the organization of the interphase microtubule network. (PMID:20861304)
• MZT Proteins Form Multi-Faceted Structural Modules in the gamma-Tubulin Ring Complex. (PMID:32610146)
• MZT2A promotes NSCLC viability and invasion by increasing Akt phosphorylation via the MOZART2 domain. (PMID:33754417)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mzt2b	ENSDARG00000057928
mus_musculus	Mzt2	ENSMUSG00000022671
rattus_norvegicus	Mzt2b	ENSRNOG00000066842

Paralogs (1): MZT2B (ENSG00000152082)

Protein

Protein identifiers

Mitotic-spindle organizing protein 2A — Q6P582 (reviewed: Q6P582)

Alternative names: Mitotic-spindle organizing protein associated with a ring of gamma-tubulin 2A

All UniProt accessions (2): Q6P582, H7C202

UniProt curated annotations — full annotation on UniProt →

Function. Required for the recruitment and the assembly of the gamma-tubulin ring complex (gTuRC) at the centrosome. The gTuRC regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments, a critical step in centrosome duplication and spindle formation.

Subunit / interactions. Associates with the gamma-tubulin ring complex (gTuRC) consisting of TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6 and gamma-tubulin TUBG1 or TUBG2; within the complex, interacts with TUBGCP2; the interaction plays a role in gTuRC activation.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle.

Similarity. Belongs to the MOZART2 family.

RefSeq proteins (1): NP_001078834* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024332	MOZART2	Family

Pfam: PF12926

UniProt features (7 total): compositionally biased region 2, modified residue 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8RX1	ELECTRON MICROSCOPY	3.57
6X0V	ELECTRON MICROSCOPY	4.5
9H9P	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P582-F1	66.27	0.21

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 (2): 34, 152

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-1640170	Cell Cycle
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 71 (showing top): GOBP_MICROTUBULE_NUCLEATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_CENTROSOME, GOBP_MICROTUBULE_POLYMERIZATION, GOCC_SPINDLE, GOCC_GAMMA_TUBULIN_COMPLEX, GOBP_MICROTUBULE_CYTOSKELETON_ORGANIZATION, GOBP_PROTEIN_POLYMERIZATION, GOBP_SUPRAMOLECULAR_FIBER_ORGANIZATION, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, GOCC_GAMMA_TUBULIN_RING_COMPLEX, BCAT_GDS748_DN, REACTOME_M_PHASE, DIDO1_TARGET_GENES, HOXB4_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): gamma-tubulin ring complex (GO:0000931), nucleoplasm (GO:0005654), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Cell Cycle, Mitotic	2
Centrosome maturation	1
Mitotic Prometaphase	1
G2/M Transition	1
M Phase	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membraneless organelle	2
binding	1
gamma-tubulin complex	1
gamma-tubulin small complex	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MZT2A	MZT1	Q08AG7	995
MZT2A	TUBG1	P23258	842
MZT2A	NEDD1	Q8NHV4	754
MZT2A	NME7	Q9Y5B8	712
MZT2A	CDK5RAP2	Q96SN8	659
MZT2A	TUBGCP3	Q96CW5	645
MZT2A	TUBGCP4	Q9UGJ1	639
MZT2A	TUBGCP5	Q96RT8	613
MZT2A	TUBGCP6	Q96RT7	608
MZT2A	TUBGCP2	Q9BSJ2	434
MZT2A	GRIP2	Q9C0E4	405
MZT2A	B8ZZ87	B8ZZ87	372
MZT2A	ERC2	O15083	370
MZT2A	MTO1	Q9Y2Z2	366
MZT2A	ACTG1	P02571	350

IntAct

63 interactions, top by confidence:

A	B	Type	Score
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
TUBGCP5	TUBG1	psi-mi:“MI:0914”(association)	0.840
MZT2A	DDX3X	psi-mi:“MI:0915”(physical association)	0.560
	MZT2A	psi-mi:“MI:0915”(physical association)	0.560
LGALS3BP	RGPD8	psi-mi:“MI:0914”(association)	0.530
TUBG2	TXNDC9	psi-mi:“MI:0914”(association)	0.530
MZT1	PCNT	psi-mi:“MI:0914”(association)	0.530
TXNDC12	TUBG1	psi-mi:“MI:0914”(association)	0.530
NEDD1	MZT2A	psi-mi:“MI:0914”(association)	0.530
TUBG2	TCP1	psi-mi:“MI:0914”(association)	0.530
	MZT2A	psi-mi:“MI:0407”(direct interaction)	0.440
Mzt2		psi-mi:“MI:0915”(physical association)	0.400
Mzt1		psi-mi:“MI:0915”(physical association)	0.400
Tubg1		psi-mi:“MI:0915”(physical association)	0.400
Tubgcp6		psi-mi:“MI:0915”(physical association)	0.400
Tubg1	BDP1	psi-mi:“MI:0914”(association)	0.350
Nedd1		psi-mi:“MI:0914”(association)	0.350
Tubgcp6	MRE11	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): MZT2A (Proximity Label-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS), MZT2A (Affinity Capture-MS)

ESM2 similar proteins: A4D2P6, A5PJV8, A6NFD8, D4AE48, O00268, O00287, O35274, O35779, O43566, P04198, P12755, P55199, Q08DA0, Q0D2I5, Q2KJ58, Q504T8, Q5XKK7, Q60698, Q61976, Q6NZ67, Q6P582, Q6R891, Q6T4P5, Q7Z6J2, Q80YR4, Q86UD0, Q86UK7, Q8BXL9, Q8CEG5, Q8R4T5, Q8TF61, Q8VCG9, Q969F2, Q969G9, Q96HZ4, Q96SB3, Q99PV5, Q9BQ61, Q9BUN5, Q9BZE9

Diamond homologs: A5PJV8, Q28DB1, Q6DC17, Q6NZ67, Q6P582, Q9CQ25

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 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
Recruitment of mitotic centrosome proteins and complexes	11	36.5×	2e-12
Recruitment of NuMA to mitotic centrosomes	11	31.3×	5e-12
Centrosome maturation	5	30.9×	3e-05
Loss of Nlp from mitotic centrosomes	6	23.2×	2e-05
Loss of proteins required for interphase microtubule organization from the centrosome	6	23.2×	2e-05
AURKA Activation by TPX2	6	22.3×	2e-05
Regulation of PLK1 Activity at G2/M Transition	6	18.6×	4e-05
Anchoring of the basal body to the plasma membrane	6	16.6×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
microtubule nucleation	9	102.1×	3e-14
cytoplasmic microtubule organization	6	37.5×	2e-06
mitotic spindle organization	5	24.7×	2e-04
mitotic cell cycle	6	14.6×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	103
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
517113	NM_080386.4(TUBA3D):c.31C>T (p.Gln11Ter)	Pathogenic
517114	NM_080386.4(TUBA3D):c.200_201dup (p.Val68fs)	Pathogenic

SpliceAI

1474 predictions. Top by Δscore:

Variant	Effect	Δscore
2:131478155:T:TA	acceptor_gain	1.0000
2:131478160:A:AG	acceptor_gain	1.0000
2:131478161:C:G	acceptor_gain	1.0000
2:131478162:A:AG	acceptor_gain	1.0000
2:131478162:A:C	acceptor_loss	1.0000
2:131478162:AGC:A	acceptor_gain	1.0000
2:131478162:AGCGC:A	acceptor_gain	1.0000
2:131478163:G:GA	acceptor_gain	1.0000
2:131478163:GC:G	acceptor_gain	1.0000
2:131478163:GCG:G	acceptor_gain	1.0000
2:131478163:GCGC:G	acceptor_gain	1.0000
2:131478163:GCGCG:G	acceptor_gain	1.0000
2:131478337:C:T	donor_gain	1.0000
2:131478383:GTCG:G	donor_gain	1.0000
2:131478386:GGTA:G	donor_loss	1.0000
2:131478387:G:GG	donor_gain	1.0000
2:131478387:GTAG:G	donor_loss	1.0000
2:131478388:T:G	donor_loss	1.0000
2:131479303:T:A	acceptor_gain	1.0000
2:131479306:A:AG	acceptor_gain	1.0000
2:131479306:A:G	acceptor_loss	1.0000
2:131479306:AGAT:A	acceptor_gain	1.0000
2:131479307:G:GT	acceptor_gain	1.0000
2:131479307:GA:G	acceptor_gain	1.0000
2:131479307:GAT:G	acceptor_gain	1.0000
2:131479307:GATG:G	acceptor_gain	1.0000
2:131479307:GATGA:G	acceptor_gain	1.0000
2:131479452:AACTG:A	donor_gain	1.0000
2:131479453:ACTG:A	donor_gain	1.0000
2:131479454:CTG:C	donor_gain	1.0000

AlphaMissense

1003 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:131492209:G:C	F56L	0.978
2:131492209:G:T	F56L	0.978
2:131492211:A:G	F56L	0.978
2:131491968:A:T	L76H	0.968
2:131492024:C:A	K57N	0.963
2:131492024:C:G	K57N	0.963
2:131491976:G:C	F73L	0.958
2:131491976:G:T	F73L	0.958
2:131491978:A:G	F73L	0.958
2:131492022:A:G	I58T	0.957
2:131491980:A:T	V72D	0.951
2:131491998:T:A	N66I	0.943
2:131492210:A:G	F56S	0.943
2:131492010:A:G	L62P	0.939
2:131492246:G:T	A44D	0.931
2:131492249:A:G	L43P	0.921
2:131492022:A:C	I58S	0.918
2:131492241:C:G	A46P	0.918
2:131492007:A:G	L63P	0.911
2:131491968:A:G	L76P	0.908
2:131491983:G:T	A71D	0.908
2:131492211:A:T	F56I	0.905
2:131492258:A:G	L40P	0.904
2:131492258:A:T	L40Q	0.904
2:131491964:C:A	K77N	0.903
2:131491964:C:G	K77N	0.903
2:131492287:C:A	K30N	0.898
2:131492287:C:G	K30N	0.898
2:131492010:A:T	L62Q	0.897
2:131491977:A:G	F73S	0.890

dbSNP variants (sampled 300 via entrez): RS1000417197 (2:131472682 A>T), RS1000676597 (2:131471562 T>A,C), RS1000752046 (2:131470772 C>T), RS1001024406 (2:131483448 A>T), RS1001305595 (2:131477504 C>G), RS1001364199 (2:131493132 G>A,T), RS1001427922 (2:131492790 TG>T,TGGGGGGAAGGG,TGG,TGGGGGGGGGGG,TGGGGGGGGGGGG), RS1001708557 (2:131488512 C>A), RS1002301268 (2:131471711 A>G), RS1002819666 (2:131477999 T>C), RS1002902032 (2:131475038 G>A), RS1002974080 (2:131474709 C>A,G), RS1003056242 (2:131485880 C>G), RS1003240692 (2:131473191 C>G), RS1003312796 (2:131472920 C>A,G)

Disease associations

OMIM: gene MIM:613449 | disease phenotypes: MIM:617928

GenCC curated gene-disease

Mondo (1): keratoconus 9 (MONDO:0054771)

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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	3
FR900359	decreases phosphorylation	1
bisphenol A	affects expression	1
sodium arsenite	decreases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	decreases expression	1
Cadmium	increases expression	1
Doxorubicin	decreases expression	1
Gasoline	increases abundance, increases expression, affects cotreatment	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	increases abundance, increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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