TUBG1

Summary

TUBG1 (tubulin gamma 1, HGNC:12417) is a protein-coding gene on chromosome 17q21.31, encoding Tubulin gamma-1 chain (P23258). Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers. It is a common-essential gene (DepMap: required in 98.3% of cancer cell lines).

This gene encodes a member of the tubulin superfamily. The encoded protein localizes to the centrosome where it binds to microtubules as part of a complex referred to as the gamma-tubulin ring complex. The protein mediates microtubule nucleation and is required for microtubule formation and progression of the cell cycle. A pseudogene of this gene is found on chromosome 7.

Source: NCBI Gene 7283 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lissencephaly spectrum disorders (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 221 total — 2 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 40
• Cancer dependency (DepMap): dependent in 98.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_001070

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12417
Approved symbol	TUBG1
Name	tubulin gamma 1
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	TUBGCP1
Ensembl gene	ENSG00000131462
Ensembl biotype	protein_coding
OMIM	191135
Entrez	7283

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 10 protein_coding, 10 retained_intron, 1 nonsense_mediated_decay

ENST00000251413, ENST00000588056, ENST00000589613, ENST00000589688, ENST00000591509, ENST00000679484, ENST00000680617, ENST00000680672, ENST00000680678, ENST00000681114, ENST00000681413, ENST00000681490, ENST00000681919, ENST00000681947, ENST00000879460, ENST00000879461, ENST00000879462, ENST00000928290, ENST00000928291, ENST00000951125, ENST00000951126

RefSeq mRNA: 1 — MANE Select: NM_001070 NM_001070

CCDS: CCDS11433

Canonical transcript exons

ENST00000251413 — 11 exons

Exon	Start	End
ENSE00001305412	42614844	42615238
ENSE00002350666	42612075	42612143
ENSE00002422147	42612427	42612506
ENSE00002879981	42609683	42609786
ENSE00003485608	42614260	42614412
ENSE00003524874	42610108	42610220
ENSE00003538826	42614496	42614657
ENSE00003564318	42613647	42613733
ENSE00003603067	42613849	42613998
ENSE00003613284	42612947	42613073
ENSE00003637771	42610423	42610590

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.9042 / max 585.0748, expressed in 1812 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160969	72.9042	1812

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.71	gold quality
right testis	UBERON:0004534	98.71	gold quality
adult organism	UBERON:0007023	97.72	gold quality
testis	UBERON:0000473	96.75	gold quality
oocyte	CL:0000023	96.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.13	gold quality
gastrocnemius	UBERON:0001388	93.06	gold quality
stromal cell of endometrium	CL:0002255	92.92	gold quality
trabecular bone tissue	UBERON:0002483	92.75	gold quality
heart left ventricle	UBERON:0002084	92.66	gold quality
cardiac ventricle	UBERON:0002082	92.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.24	gold quality
muscle of leg	UBERON:0001383	92.19	gold quality
prefrontal cortex	UBERON:0000451	92.11	gold quality
apex of heart	UBERON:0002098	91.89	gold quality
secondary oocyte	CL:0000655	91.86	gold quality
body of pancreas	UBERON:0001150	91.81	gold quality
embryo	UBERON:0000922	91.61	gold quality
body of stomach	UBERON:0001161	91.56	gold quality
lower esophagus	UBERON:0013473	91.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.55	gold quality
Brodmann (1909) area 10	UBERON:0013541	91.47	gold quality
lower esophagus mucosa	UBERON:0035834	91.31	gold quality
esophagus	UBERON:0001043	91.05	gold quality
right frontal lobe	UBERON:0002810	90.92	gold quality
esophagus mucosa	UBERON:0002469	90.89	gold quality
ganglionic eminence	UBERON:0004023	90.84	gold quality
right atrium auricular region	UBERON:0006631	90.78	gold quality
heart	UBERON:0000948	90.77	gold quality
left adrenal gland cortex	UBERON:0035825	90.76	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.05
E-HCAD-13	yes	19.76
E-MTAB-6524	no	131.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

33 targeting TUBG1, 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-3910	99.95	71.13	2227
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-1910-3P	98.44	67.51	1695

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 38)

• the 2.7-A crystal structure of human gamma-tubulin bound to GTP-gammaS (a non-hydrolysable GTP analogue) (PMID:15917813)
• analysis of human ninein isoforms that are regulated by centrosomal targeting signals and bind to gamma-tubulin (PMID:17102634)
• Data suggest that aberrant expression and interactions of betaIII-tubulin and gamma-tubulin may be linked to malignant changes in glial cells. (PMID:17406983)
• GSK-3beta regulates the localization of gamma-tubulin ring complex, including GCP5, to the spindle poles, thereby controlling the formation of proper mitotic spindles (PMID:18316369)
• The axial elastic modulus of tubulin diminishes as the length of the monomer increases. (PMID:18621829)
• Increased expression of centrosomal TUBG in atypical ductal hyperplasia and carcinoma of the breast is reported. (PMID:19215229)
• Stability of the small gamma-tubulin complex (gamma tubulin/GCP2/GCP3) requires HCA66, a protein of the centrosome and the nucleolus. (PMID:19299467)
• Data suggest that sequential phosphorylation of Nedd1 by Cdk1 and Plk1 plays a role in targeting gamma tubulin ring complex to the centrosome by promoting the interaction of Nedd1 with the gammaTuRC component gamma-tubulin, during mitosis. (PMID:19509060)
• Plk1-dependent recruitment of gamma-tubulin complexes to mitotic centrosomes involves multiple PCM components (PMID:19543530)
• SADB kinase activity controls centrosome homeostasis by regulating phosphorylation of gamma-tubulin. (PMID:19648910)
• a direct interaction with NEDD1 regulates gamma-tubulin recruitment to the centrosome (PMID:20224777)
• in transformed as well as in non-transformed interphase mammalian cells gamma-tubulin is present not only in cytoplasm but also in nuclei and nucleoli where it can be translocated during mitosis (PMID:21465471)
• The data presented here indicate that gamma-tubulin has a profound relationship with actin filament dynamics (PMID:21473851)
• These results thus report for the first time the identification of Cep70 as an important centrosomal protein that interacts with gamma-tubulin and underscore its critical role in the regulation of mitotic spindle assembly. (PMID:21795687)
• overexpression of Cdk1 or BRCA1 greatly expands the gamma-tubulin coating of microtubules, suggesting that the microtubule-bound gamma-tubulin is involved in DNA damage response. (PMID:21951856)
• Our results reveal for the first time an increased expression of TUBG1 and TUBG2 in lung cancer (PMID:22806905)
• Nek9 phosphorylates NEDD1 on Ser377 driving its recruitment and thereby that of gamma-tubulin to the centrosome in mitotic cells. (PMID:22818914)
• Recombinant gamma-tubulin can be phosphorylated by Cdk1-cyclin B or Brsk1 and dephosphorylated by Ppp4c-R2-R3A in vitro. (PMID:23966160)
• Gamma tubulin expression was associated with patients’ age, astrocytoma grade, respectability, patient survival and performance. These factors may be important prognostic indicators for patients with astrocytomas. (PMID:24620973)
• In this study, the molecular basis of interaction between two lateral gamma-tubulin units within the gamma-tubulin ring complex were elucidated by making extensive use of molecular mechanics and molecular dynamics techniques. (PMID:25031076)
• Results show that CUL4A- and CUL4B-mediated polyubiquitination of gamma-tubulin for its degradation. (PMID:25542213)
• a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers (PMID:25830658)
• While binding to gamma-tubulin may help target APC to the site of microtubule nucleation complexes, additional C-terminal sequences of APC are required to stimulate and stabilize microtubule growth. (PMID:26556314)
• All GCPs are incorporated into the helix via lateral interactions between their N-terminal domains, whereas the C-terminal domains mediate longitudinal interactions with gamma-tubulin. (PMID:27660388)
• that in the face of predominant gamma-tubulin-1 expression, the accumulation of gamma-tubulin-2 in mature neurons and neuroblastoma cells during oxidative stress may denote a prosurvival role of gamma-tubulin-2 in neurons (PMID:28119396)
• CCT actively promotes the formation of conformationally different aggregates of gamma-tubulin, a non-amyloidogenic CCT client protein, which are mediated by specific CCT-gamma-tubulin interactions. (PMID:29339327)
• induced FBXL13 expression downregulates centrosomal gamma-tubulin and disrupts centrosomal microtubule arrays. In addition, depletion of FBXL13 induces high levels of CEP192 and gamma-tubulin at the centrosomes with the consequence of defects in cell motility. (PMID:29348145)
• Four novel heterozygous variants in TUBG1 were identified in patients with malformations of cortical development. (PMID:29706637)
• Our findings suggest that level of gamma-tubulin expression may have an impact on patient survival at more advanced non-small cell lung cancer stages (PMID:30010174)
• Study investigated the consequences of four human malformations of cortical development-related TUBG1 variants by using in utero electroporation and a knock-in Tubg1Y92C/+ mouse model and show that pathogenic TUBG1 variants affect neuronal positioning by disrupting neuronal migration and affecting microtubule dynamics rather than centrosomal positioning or nucleation ability. (PMID:31086189)
• Data present two patients with novel de novo tubulin gamma 1 (TUBG1) mutations with milder neurodevelopmental disorders. (PMID:31151415)
• TACC3 phosphorylation stabilizes gamma- tubulin ring complex assembly and thereby regulates formation of centrosomal asters. (PMID:31823729)
• Gravin-associated kinase signaling networks coordinate gamma-tubulin organization at mitotic spindle poles. (PMID:32732289)
• Biochemical reconstitutions reveal principles of human gamma-TuRC assembly and function. (PMID:33496729)
• Microtubule-associated proteins promote microtubule generation in the absence of gamma-tubulin in human colon cancer cells. (PMID:34779859)
• Upregulation of TUBG1 expression promotes hepatocellular carcinoma development. (PMID:36792863)
• Centrosome Movements Are TUBG1-Dependent. (PMID:37685969)
• TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways. (PMID:37806848)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tubg1	ENSDARG00000015610
mus_musculus	Tubg1	ENSMUSG00000035198
rattus_norvegicus	Tubg1	ENSRNOG00000020213
drosophila_melanogaster	gammaTub23C	FBGN0260639

Paralogs (23): TUBG2 (ENSG00000037042), TUBE1 (ENSG00000074935), TUBA3D (ENSG00000075886), TUBB1 (ENSG00000101162), TUBB4A (ENSG00000104833), TUBD1 (ENSG00000108423), TUBA1B (ENSG00000123416), TUBA4A (ENSG00000127824), TUBB2A (ENSG00000137267), TUBB2B (ENSG00000137285), TUBA3E (ENSG00000152086), TUBA1A (ENSG00000167552), TUBA1C (ENSG00000167553), TUBB8B (ENSG00000173213), TUBB6 (ENSG00000176014), TUBAL3 (ENSG00000178462), TUBA8 (ENSG00000183785), TUBB4B (ENSG00000188229), TUBB (ENSG00000196230), TUBA3C (ENSG00000198033), TUBA4B (ENSG00000243910), TUBB3 (ENSG00000258947), TUBB8 (ENSG00000261456)

Protein

Protein identifiers

Tubulin gamma-1 chain — P23258 (reviewed: P23258)

Alternative names: Gamma-1-tubulin, Gamma-tubulin complex component 1

All UniProt accessions (4): A0A7P0T9G6, P23258, K7EIS0, K7EKE5

UniProt curated annotations — full annotation on UniProt →

Function. Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers. Gamma-tubulin is a key component of the gamma-tubulin ring complex (gTuRC) which mediates microtubule nucleation. 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. Component of the gamma-tubulin ring complex (gTuRC) consisting of TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6 and gamma-tubulin TUBG1 or TUBG2. TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6 assemble in a 5:5:2:1:1 stoichiometry; each is associated with a gamma-tubulin, thereby arranging 14 gamma-tubulins in a helical manner. Gamma-tubulin at the first position is blocked by TUBGCP3 at the last position, allowing 13 protafilaments to grow into a microtubule. The gTuRC (via TUBGCP3 and TUBGCP6) interacts with ACTB and MZT1; the interactions form a luminal bridge that stabilizes the initial structure during complex assembly. The gTuRC (via TUBGCP2) interacts with MZT2A/MZT2B and CDK5RAP2 (via CM1 motif); the interactions play a role in gTuRC activation. Interacts with alpha-beta tubulin heterodimers; the interaction allows microtubules to nucleate from the gTuRC. Interacts with B9D2. Interacts with CDK5RAP2; the interaction is leading to centrosomal localization of TUBG1 and CDK5RAP2. Interacts with CIMAP3. Interacts with SAS6 and NUP62 at the centrosome. Interacts with EML3 (phosphorylated at ‘Thr-881’) and HAUS8. Interacts with DNM2; this interaction may participate in centrosome cohesion. Interacts with CCDC66.

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

Post-translational modifications. Phosphorylation at Ser-131 by BRSK1 regulates centrosome duplication, possibly by mediating relocation of gamma-tubulin and its associated proteins from the cytoplasm to the centrosome.

Disease relevance. Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) [MIM:615412] A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include early-onset seizures, microcephaly, spastic tetraplegia, and various malformations of cortical development, such as agyria, posterior or frontal pachygyria, thick cortex, and subcortical band heterotopia and thin corpus callosum in some patients. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the tubulin family.

RefSeq proteins (1): NP_001061* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000217	Tubulin	Family
IPR002454	Gamma_tubulin	Family
IPR003008	Tubulin_FtsZ_GTPase	Domain
IPR008280	Tub_FtsZ_C	Homologous_superfamily
IPR017975	Tubulin_CS	Conserved_site
IPR018316	Tubulin/FtsZ_2-layer-sand-dom	Domain
IPR023123	Tubulin_C	Homologous_superfamily
IPR036525	Tubulin/FtsZ_GTPase_sf	Homologous_superfamily
IPR037103	Tubulin/FtsZ-like_C	Homologous_superfamily

Pfam: PF00091, PF03953

Enzyme classification (BRENDA):

• EC 3.6.5.6 — tubulin GTPase (BRENDA: 20 organisms, 31 substrates, 20 inhibitors, 10 Km, 16 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.008–0.042	8

UniProt features (48 total): helix 19, strand 18, sequence variant 4, turn 2, sequence conflict 2, chain 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3CB2	X-RAY DIFFRACTION	2.3
1Z5V	X-RAY DIFFRACTION	2.71
1Z5W	X-RAY DIFFRACTION	3
8RX1	ELECTRON MICROSCOPY	3.57
8Q62	ELECTRON MICROSCOPY	3.72
6V5V	ELECTRON MICROSCOPY	3.8
7AS4	ELECTRON MICROSCOPY	4.13
6V6S	ELECTRON MICROSCOPY	4.3
8VA2	ELECTRON MICROSCOPY	4.5
9H9P	ELECTRON MICROSCOPY	4.5
9QVN	ELECTRON MICROSCOPY	4.7
7QJ0	ELECTRON MICROSCOPY	5.32
9QVM	ELECTRON MICROSCOPY	6.8
7QJ1	ELECTRON MICROSCOPY	7
8VRD	ELECTRON MICROSCOPY	7
7QJD	ELECTRON MICROSCOPY	7.1
7QJ3	ELECTRON MICROSCOPY	7.6
8VRJ	ELECTRON MICROSCOPY	7.7
7QJ6	ELECTRON MICROSCOPY	7.8
7QJE	ELECTRON MICROSCOPY	7.8
7QJ9	ELECTRON MICROSCOPY	8.1
8VRK	ELECTRON MICROSCOPY	8.5
7QJ2	ELECTRON MICROSCOPY	8.6
7QJ5	ELECTRON MICROSCOPY	8.7
7QJ7	ELECTRON MICROSCOPY	8.7
7QJ8	ELECTRON MICROSCOPY	8.7
7QJ4	ELECTRON MICROSCOPY	9
7QJA	ELECTRON MICROSCOPY	9.2
7QJB	ELECTRON MICROSCOPY	9.2
7QJC	ELECTRON MICROSCOPY	16.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23258-F1	91.80	0.78

Functional residue map

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

Ligand- & substrate-binding residues (1): 142–148

Post-translational modifications (1): 131

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-1640170	Cell Cycle
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
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: 355 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, BASSO_B_LYMPHOCYTE_NETWORK, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MICROTUBULE_NUCLEATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, PATIL_LIVER_CANCER, GOBP_ORGANELLE_FISSION, PID_PLK1_PATHWAY, FOURNIER_ACINAR_DEVELOPMENT_LATE_DN, GOCC_CENTROSOME, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_MITOTIC_CELL_CYCLE

GO Biological Process (8): mitotic sister chromatid segregation (GO:0000070), meiotic spindle organization (GO:0000212), microtubule cytoskeleton organization (GO:0000226), mitotic cell cycle (GO:0000278), microtubule nucleation (GO:0007020), mitotic spindle organization (GO:0007052), cytoplasmic microtubule organization (GO:0031122), microtubule-based process (GO:0007017)

GO Molecular Function (6): structural constituent of cytoskeleton (GO:0005200), GTP binding (GO:0005525), identical protein binding (GO:0042802), microtubule nucleator activity (GO:0140490), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (24): pericentriolar material (GO:0000242), condensed nuclear chromosome (GO:0000794), gamma-tubulin complex (GO:0000930), gamma-tubulin ring complex (GO:0000931), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), spindle (GO:0005819), polar microtubule (GO:0005827), cytosol (GO:0005829), cytoplasmic microtubule (GO:0005881), cell leading edge (GO:0031252), ciliary basal body (GO:0036064), neuron projection (GO:0043005), apical part of cell (GO:0045177), recycling endosome (GO:0055037), non-motile cilium (GO:0097730), mitotic spindle microtubule (GO:1990498), cytoskeleton (GO:0005856), microtubule (GO:0005874), spindle microtubule (GO:0005876), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Cell Cycle, Mitotic	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	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	5
microtubule organizing center	4
intracellular membraneless organelle	3
mitotic nuclear division	2
spindle organization	2
cytoskeleton organization	2
microtubule cytoskeleton organization	2
spindle microtubule	2
cytoplasm	2
cilium	2
sister chromatid segregation	1
mitotic cell cycle process	1
meiotic cell cycle	1
meiotic cell cycle process	1
microtubule-based process	1
cell cycle	1
microtubule polymerization	1
mitotic cell cycle	1
microtubule cytoskeleton organization involved in mitosis	1
supramolecular fiber organization	1
cellular process	1
structural molecule activity	1
cytoskeleton	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
molecular template activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
centrosome	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
protein-containing complex	1
gamma-tubulin complex	1
gamma-tubulin small complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
centriole	1

Protein interactions and networks

STRING

2336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUBG1	TUBGCP6	Q96RT7	946
TUBG1	TUBGCP4	Q9UGJ1	929
TUBG1	MZT1	Q08AG7	905
TUBG1	TUBGCP3	Q96CW5	902
TUBG1	PLK4	O00444	900
TUBG1	TUBGCP2	Q9BSJ2	884
TUBG1	CPAP	Q9HC77	875
TUBG1	HAUS6	Q7Z4H7	871
TUBG1	CEP135	Q66GS9	845
TUBG1	B8ZZ87	B8ZZ87	843
TUBG1	MZT2A	Q6P582	842
TUBG1	TUBGCP5	Q96RT8	823
TUBG1	SASS6	Q6UVJ0	820
TUBG1	PCNT	O95613	819
TUBG1	NUMA1	Q14980	800

IntAct

156 interactions, top by confidence:

A	B	Type	Score
RYBP	CSNK2A2	psi-mi:“MI:0914”(association)	0.900
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
TUBGCP5	TUBG1	psi-mi:“MI:0914”(association)	0.840
TUBG1	TUBGCP3	psi-mi:“MI:0914”(association)	0.790
MZT2B	TUBG1	psi-mi:“MI:0914”(association)	0.770
MZT1	TUBG1	psi-mi:“MI:0915”(physical association)	0.770
TUBG1	MZT2B	psi-mi:“MI:0915”(physical association)	0.770
TUBG1	TUBG1	psi-mi:“MI:0407”(direct interaction)	0.760
TUBG1	TUBG1	psi-mi:“MI:2364”(proximity)	0.760
NME7	TUBG1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DISC1	PCNT	psi-mi:“MI:0915”(physical association)	0.670
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
MARK4	TUBG1	psi-mi:“MI:0915”(physical association)	0.620
TUBG1	MARK4	psi-mi:“MI:0915”(physical association)	0.620
Mzt2	TUBG1	psi-mi:“MI:0914”(association)	0.560
TUBGCP4	TUBG1	psi-mi:“MI:0915”(physical association)	0.560
Mad2l1	BUB1B	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

BioGRID (556): TUBG1 (Reconstituted Complex), TUBG1 (Affinity Capture-MS), TUBG1 (Affinity Capture-MS), TUBG1 (Affinity Capture-MS), TUBG1 (Affinity Capture-Western), TUBG1 (Affinity Capture-Western), TUBG1 (Biochemical Activity), TUBG1 (Affinity Capture-MS), TUBG1 (Co-fractionation), TUBG1 (Reconstituted Complex), TUBG1 (Proximity Label-MS), TUBG1 (Affinity Capture-MS), AUP1 (Affinity Capture-MS), CAMK2G (Affinity Capture-MS), CCT6A (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8EV45, C9WPN6, F1QGW6, F6RQL9, O73723, O77676, P00516, P0C605, P20461, P23258, P23330, P31321, P32392, P35250, P41091, P53033, P61157, P61158, P62482, P62483, P81795, P83887, P83888, Q05B83, Q0VCD2, Q13126, Q13303, Q13976, Q27955, Q2KHU8, Q2KJ81, Q2VIR3, Q32KM1, Q4V7C7, Q5R797, Q5R8R1, Q5ZHS1, Q5ZMS3, Q641P0, Q641W4

Diamond homologs: A0A644F0Y1, O04386, O17449, O49068, O93807, P04690, P05220, P07437, P10653, P10875, P10876, P10878, P11482, P11833, P12456, P14140, P14643, P18695, P20365, P22012, P22013, P22852, P23257, P23258, P23330, P25295, P31863, P32348, P32882, P32925, P34475, P34785, P34786, P34787, P38557, P38558, P40633, P40904, P41741, P42271

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
NUMA1	up-regulates	TUBG1	binding
BRSK1	up-regulates	TUBG1	phosphorylation
“vincaleukoblastine sulfate”	“down-regulates activity”	TUBG1	“chemical inhibition”
CDK5RAP2	“up-regulates activity”	TUBG1	binding
NUP62	“up-regulates activity”	TUBG1	binding
TUBG1	up-regulates	Microtubule_polimerization
“g-TuRC complex”	“up-regulates activity”	TUBG1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 162 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
Centrosome maturation	11	27.4×	3e-11
Recruitment of mitotic centrosome proteins and complexes	20	26.7×	7e-21
Recruitment of NuMA to mitotic centrosomes	20	22.9×	1e-19
AURKA Activation by TPX2	12	17.9×	4e-10
Loss of Nlp from mitotic centrosomes	11	17.1×	3e-09
Loss of proteins required for interphase microtubule organization from the centrosome	11	17.1×	3e-09
Intrinsic Pathway for Apoptosis	5	14.3×	7e-04
Regulation of PLK1 Activity at G2/M Transition	11	13.7×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
microtubule nucleation	10	47.3×	5e-12
centriole replication	5	27.8×	1e-04
spindle assembly	8	26.9×	3e-07
positive regulation of telomere maintenance	6	23.2×	4e-05
cytoplasmic microtubule organization	7	18.2×	3e-05
mitotic spindle organization	5	10.3×	9e-03
JNK cascade	5	10.3×	9e-03
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	6	9.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	10
Uncertain significance	74
Likely benign	93
Benign	20

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
65397	NM_001070.5(TUBG1):c.1160T>C (p.Leu387Pro)	Pathogenic
65399	NM_001070.5(TUBG1):c.991A>C (p.Thr331Pro)	Pathogenic
1298704	NM_001070.5(TUBG1):c.1024G>A (p.Glu342Lys)	Likely pathogenic
1526152	NM_001070.5(TUBG1):c.821C>A (p.Thr274Asn)	Likely pathogenic
1703182	NM_001070.5(TUBG1):c.725C>T (p.Thr242Ile)	Likely pathogenic
2430135	NM_001070.5(TUBG1):c.421A>C (p.Ile141Leu)	Likely pathogenic
3236666	NM_001070.5(TUBG1):c.202G>T (p.Asp68Tyr)	Likely pathogenic
3330224	NM_001070.5(TUBG1):c.41G>A (p.Gly14Asp)	Likely pathogenic
3376145	NM_001070.5(TUBG1):c.843+2_843+5del	Likely pathogenic
392052	NM_001070.5(TUBG1):c.821C>T (p.Thr274Ile)	Likely pathogenic
65398	NM_001070.5(TUBG1):c.275A>G (p.Tyr92Cys)	Likely pathogenic
996662	NM_001070.5(TUBG1):c.769A>T (p.Ile257Phe)	Likely pathogenic

SpliceAI

1171 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42609785:GA:G	donor_gain	1.0000
17:42609787:G:GG	donor_gain	1.0000
17:42610203:G:GT	donor_gain	1.0000
17:42610272:G:T	donor_gain	1.0000
17:42610276:G:GT	donor_gain	1.0000
17:42610417:T:TA	acceptor_gain	1.0000
17:42610419:ACAG:A	acceptor_loss	1.0000
17:42610420:CAG:C	acceptor_loss	1.0000
17:42610421:A:AG	acceptor_gain	1.0000
17:42610422:G:GG	acceptor_gain	1.0000
17:42610422:G:GT	acceptor_loss	1.0000
17:42610422:GGCA:G	acceptor_gain	1.0000
17:42610553:G:GT	donor_gain	1.0000
17:42612069:GTACA:G	acceptor_loss	1.0000
17:42612070:TACA:T	acceptor_loss	1.0000
17:42612072:CAGG:C	acceptor_loss	1.0000
17:42612073:A:AG	acceptor_gain	1.0000
17:42612073:A:G	acceptor_loss	1.0000
17:42612073:AG:A	acceptor_gain	1.0000
17:42612074:G:GG	acceptor_gain	1.0000
17:42612074:GG:G	acceptor_gain	1.0000
17:42612074:GGGA:G	acceptor_gain	1.0000
17:42612140:AGAGG:A	donor_loss	1.0000
17:42612143:GGTA:G	donor_loss	1.0000
17:42612144:G:GA	donor_loss	1.0000
17:42612145:TAAGT:T	donor_loss	1.0000
17:42612422:TGCAG:T	acceptor_loss	1.0000
17:42612423:GCAGG:G	acceptor_loss	1.0000
17:42612424:CAGGG:C	acceptor_loss	1.0000
17:42612425:A:C	acceptor_loss	1.0000

AlphaMissense

2974 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42609768:G:C	G11R	1.000
17:42609769:G:A	G11D	1.000
17:42609769:G:T	G11V	1.000
17:42609776:C:G	C13W	1.000
17:42609778:G:A	G14D	1.000
17:42609778:G:T	G14V	1.000
17:42610110:G:T	G18W	1.000
17:42610122:T:A	W22R	1.000
17:42610122:T:C	W22R	1.000
17:42610559:C:A	A100D	1.000
17:42610566:C:A	N102K	1.000
17:42610566:C:G	N102K	1.000
17:42610570:T:A	W104R	1.000
17:42610570:T:C	W104R	1.000
17:42610572:G:C	W104C	1.000
17:42610572:G:T	W104C	1.000
17:42610580:G:A	G107E	1.000
17:42612115:G:C	R124P	1.000
17:42612445:T:C	S140P	1.000
17:42612446:C:T	S140F	1.000
17:42612454:G:A	G143R	1.000
17:42612454:G:C	G143R	1.000
17:42612454:G:T	G143W	1.000
17:42612455:G:A	G143E	1.000
17:42612455:G:T	G143V	1.000
17:42612457:G:A	G144R	1.000
17:42612457:G:C	G144R	1.000
17:42612457:G:T	G144W	1.000
17:42612458:G:A	G144E	1.000
17:42612458:G:T	G144V	1.000

dbSNP variants (sampled 300 via entrez): RS1000206034 (17:42614761 T>C), RS1002691936 (17:42611962 A>G), RS1002796516 (17:42608940 G>A,C), RS1003357029 (17:42615588 C>A), RS1003650364 (17:42608896 T>C), RS1003935631 (17:42613536 A>C), RS1004251331 (17:42613832 G>A), RS1004547570 (17:42613500 C>T), RS1005304336 (17:42609623 C>T), RS1005551221 (17:42613266 A>G), RS1006279481 (17:42615275 T>A), RS1006363576 (17:42609100 C>G), RS1007135054 (17:42611160 C>G,T), RS1007609521 (17:42611182 G>C,T), RS1007882705 (17:42609583 A>C)

Disease associations

OMIM: gene MIM:191135 | disease phenotypes: MIM:615412, MIM:607432

GenCC curated gene-disease

Disease	Classification	Inheritance
complex cortical dysplasia with other brain malformations 4	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
lissencephaly spectrum disorders	Definitive	AD

Mondo (2): complex cortical dysplasia with other brain malformations 4 (MONDO:0014171), lissencephaly spectrum disorders (MONDO:0018838)

Orphanet (1): Lissencephaly (Orphanet:48471)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000174	Abnormal palate morphology
HP:0000252	Microcephaly
HP:0000337	Broad forehead
HP:0000377	Abnormal pinna morphology
HP:0000518	Cataract
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001302	Pachygyria
HP:0001627	Abnormal heart morphology
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001636	Tetralogy of Fallot
HP:0001680	Coarctation of aorta
HP:0001999	Abnormal facial shape
HP:0002172	Postural instability
HP:0002198	Dilated fourth ventricle
HP:0002311	Incoordination
HP:0002354	Memory impairment
HP:0002510	Spastic tetraplegia
HP:0005160	Total anomalous pulmonary venous return
HP:0006891	Thick cerebral cortex

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010241_34	Apolipoprotein A1 levels	1.000000e-16
GCST010242_21	HDL cholesterol levels	2.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D054082	Lissencephaly	C10.500.507.450.499; C16.131.666.507.450.499

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects binding, increases reaction, decreases expression (+1 more)	5
Valproic Acid	affects expression, increases expression, increases methylation	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
diallyl trisulfide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
picoxystrobin	increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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