TUBGCP2

Summary

TUBGCP2 (tubulin gamma complex component 2, HGNC:18599) is a protein-coding gene on chromosome 10q26.3, encoding Gamma-tubulin complex component 2 (Q9BSJ2). Component of the gamma-tubulin ring complex (gTuRC) which mediates microtubule nucleation. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines).

Predicted to enable gamma-tubulin binding activity. Predicted to contribute to microtubule minus-end binding activity. Involved in brain development and neuron migration. Located in centrosome; ciliary basal body; and nucleoplasm. Implicated in pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures.

Source: NCBI Gene 10844 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 238 total — 1 pathogenic
• Phenotypes (HPO): 25
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_006659

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18599
Approved symbol	TUBGCP2
Name	tubulin gamma complex component 2
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Aliases	GCP2, Spc97p, SPBC97, hGCP2, ALP4
Ensembl gene	ENSG00000130640
Ensembl biotype	protein_coding
OMIM	617817
Entrez	10844

Gene structure

Transcript identifiers

Ensembl transcripts: 54 — 30 protein_coding, 10 nonsense_mediated_decay, 9 retained_intron, 5 protein_coding_CDS_not_defined

ENST00000252936, ENST00000368562, ENST00000417178, ENST00000424450, ENST00000470829, ENST00000477923, ENST00000480198, ENST00000482278, ENST00000487796, ENST00000543663, ENST00000682093, ENST00000682123, ENST00000682161, ENST00000682256, ENST00000682332, ENST00000682515, ENST00000682591, ENST00000682631, ENST00000682712, ENST00000682905, ENST00000682990, ENST00000683014, ENST00000683031, ENST00000683060, ENST00000683308, ENST00000683383, ENST00000683552, ENST00000683612, ENST00000683673, ENST00000683704, ENST00000683786, ENST00000683829, ENST00000684421, ENST00000684478, ENST00000684487, ENST00000855454, ENST00000855455, ENST00000855456, ENST00000855457, ENST00000855458, ENST00000855459, ENST00000855460, ENST00000916723, ENST00000916724, ENST00000916725, ENST00000968923, ENST00000968924, ENST00000968925, ENST00000968926, ENST00000968927, ENST00000968928, ENST00000968929, ENST00000968930, ENST00000968931

RefSeq mRNA: 3 — MANE Select: NM_006659 NM_001256617, NM_001256618, NM_006659

CCDS: CCDS58104, CCDS58105, CCDS7676

Canonical transcript exons

ENST00000252936 — 18 exons

Exon	Start	End
ENSE00000876614	133297952	133298111
ENSE00001000886	133283882	133284002
ENSE00001152658	133283078	133283221
ENSE00001152678	133285085	133285213
ENSE00001152687	133285456	133285628
ENSE00001152693	133288129	133288309
ENSE00001152700	133288840	133289020
ENSE00001610338	133293562	133293769
ENSE00001613573	133289824	133289969
ENSE00001663437	133293039	133293238
ENSE00001762377	133292499	133292688
ENSE00003461573	133299427	133299603
ENSE00003470031	133282223	133282342
ENSE00003598346	133299985	133300113
ENSE00003656882	133281273	133281436
ENSE00003692697	133302792	133302980
ENSE00003750205	133278635	133279901
ENSE00003911726	133308823	133308872

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.3001 / max 250.1134, expressed in 1818 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112112	20.5598	1813
112114	6.7721	1740
112113	3.0115	1359
112111	0.8737	214
112109	0.0710	33
112110	0.0119	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.32	gold quality
metanephros cortex	UBERON:0010533	95.08	gold quality
lower esophagus mucosa	UBERON:0035834	94.95	gold quality
skin of leg	UBERON:0001511	94.83	gold quality
skin of abdomen	UBERON:0001416	94.82	gold quality
mucosa of transverse colon	UBERON:0004991	94.74	gold quality
adenohypophysis	UBERON:0002196	94.63	gold quality
granulocyte	CL:0000094	94.58	gold quality
right ovary	UBERON:0002118	94.51	gold quality
left ovary	UBERON:0002119	94.40	gold quality
right adrenal gland cortex	UBERON:0035827	94.27	gold quality
right lobe of thyroid gland	UBERON:0001119	94.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.19	gold quality
left lobe of thyroid gland	UBERON:0001120	94.14	gold quality
right adrenal gland	UBERON:0001233	94.09	gold quality
left uterine tube	UBERON:0001303	94.07	gold quality
right testis	UBERON:0004534	94.05	gold quality
left testis	UBERON:0004533	94.03	gold quality
left adrenal gland cortex	UBERON:0035825	94.03	gold quality
apex of heart	UBERON:0002098	93.93	gold quality
cerebellar hemisphere	UBERON:0002245	93.84	gold quality
cerebellar cortex	UBERON:0002129	93.74	gold quality
spleen	UBERON:0002106	93.72	gold quality
ectocervix	UBERON:0012249	93.70	gold quality
left adrenal gland	UBERON:0001234	93.69	gold quality
pituitary gland	UBERON:0000007	93.66	gold quality
right lung	UBERON:0002167	93.65	gold quality
right frontal lobe	UBERON:0002810	93.61	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	7.56
E-ANND-3	yes	7.17
E-HCAD-31	no	2.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting TUBGCP2, 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-3667-3P	99.99	67.17	1636
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-6779-3P	97.51	65.82	789
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-4436B-5P	96.71	68.37	1346

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• Stability of the small gamma-tubulin complex (gamma tubulin/GCP2/GCP3) requires HCA66, a protein of the centrosome and the nucleolus. (PMID:19299467)
• Authors show genetically that GCP3/Spc98 function is fully conserved with Alp6 across species but that functional differences exist between GCP2/Spc97 and Alp4. (PMID:23886939)
• Pathogenic variants in TUBGCP2 cause an autosomal recessive neurodevelopmental trait consisting of a neuronal migration disorder. (PMID:31630790)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tubgcp2	ENSDARG00000013079
mus_musculus	Tubgcp2	ENSMUSG00000025474
rattus_norvegicus	Tubgcp2	ENSRNOG00000018137
drosophila_melanogaster	Grip84	FBGN0026430
drosophila_melanogaster	t-Grip84	FBGN0035800

Paralogs (4): TUBGCP3 (ENSG00000126216), TUBGCP6 (ENSG00000128159), TUBGCP4 (ENSG00000137822), TUBGCP5 (ENSG00000275835)

Protein

Protein identifiers

Gamma-tubulin complex component 2 — Q9BSJ2 (reviewed: Q9BSJ2)

Alternative names: Gamma-ring complex protein 103 kDa, Spindle pole body protein Spc97 homolog

All UniProt accessions (12): Q9BSJ2, A0A804HI27, A0A804HJ08, A0A804HJH7, A0A804HJQ4, A0A804HJS9, A0A804HK74, A0A804HL05, A0A804HL95, A0A804HLH6, F2Z2B9, R4GMM4

UniProt curated annotations — full annotation on UniProt →

Function. 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. Plays a role in neuronal migration.

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 ATF5; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome.

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

Tissue specificity. Ubiquitously expressed.

Disease relevance. Cortical dysplasia, complex, with other brain malformations 15 (CDCBM15) [MIM:618737] An autosomal recessive disorder characterized by global developmental delay, variably impaired intellectual development, speech delay, facial dysmorphism, microcephaly, and varying degrees of cortical malformations including pachygyria, thin corpus callosum and subcortical band heterotopia. Most patients have generalized seizures. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TUBGCP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BSJ2-1	1	yes
Q9BSJ2-3	2
Q9BSJ2-4	3

RefSeq proteins (3): NP_001243546, NP_001243547, NP_006650* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007259	GCP	Family
IPR040457	GCP_C	Domain
IPR041470	GCP_N	Domain
IPR042241	GCP_C_sf	Homologous_superfamily

Pfam: PF04130, PF17681

UniProt features (14 total): sequence variant 6, sequence conflict 3, splice variant 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

28 structures.

PDB	Method	Resolution (Å)
8RX1	ELECTRON MICROSCOPY	3.57
8Q62	ELECTRON MICROSCOPY	3.72
6V6B	ELECTRON MICROSCOPY	3.8
7AS4	ELECTRON MICROSCOPY	4.13
6V6S	ELECTRON MICROSCOPY	4.3
6X0V	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
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
9I8G	ELECTRON MICROSCOPY	22.4
9I8H	ELECTRON MICROSCOPY	23.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSJ2-F1	76.27	0.30

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 (1): 83

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes

MSigDB gene sets: 223 (showing top): GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, WHITEHURST_PACLITAXEL_SENSITIVITY, GOBP_NEUROGENESIS, GOBP_MICROTUBULE_NUCLEATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, MARTINEZ_RB1_TARGETS_UP, GOCC_CENTROSOME, GOBP_ORGANELLE_ASSEMBLY, GOBP_NEURON_MIGRATION, GOBP_MITOTIC_CELL_CYCLE, GOBP_HEAD_DEVELOPMENT, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, MORF_PML, GOBP_SPINDLE_ASSEMBLY, MORF_IKBKG

GO Biological Process (9): mitotic cell cycle (GO:0000278), neuron migration (GO:0001764), microtubule nucleation (GO:0007020), brain development (GO:0007420), cytoplasmic microtubule organization (GO:0031122), spindle assembly (GO:0051225), meiotic cell cycle (GO:0051321), protein-containing complex assembly (GO:0065003), microtubule cytoskeleton organization (GO:0000226)

GO Molecular Function (3): gamma-tubulin binding (GO:0043015), protein binding (GO:0005515), microtubule minus-end binding (GO:0051011)

GO Cellular Component (12): spindle pole (GO:0000922), gamma-tubulin complex (GO:0000930), nucleoplasm (GO:0005654), centrosome (GO:0005813), microtubule organizing center (GO:0005815), cytosol (GO:0005829), cytoplasmic microtubule (GO:0005881), membrane (GO:0016020), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), microtubule (GO:0005874)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Centrosome maturation	1
Mitotic Prometaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
microtubule organizing center	3
cell cycle	2
microtubule cytoskeleton organization	2
microtubule cytoskeleton	2
cytoplasm	2
mitotic nuclear division	1
cell migration	1
generation of neurons	1
microtubule polymerization	1
central nervous system development	1
animal organ development	1
head development	1
supramolecular fiber organization	1
spindle organization	1
chromosome segregation	1
membraneless organelle assembly	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
cellular component assembly	1
protein-containing complex organization	1
cytoskeleton organization	1
microtubule-based process	1
tubulin binding	1
binding	1
microtubule binding	1
spindle	1
protein-containing complex	1
nuclear lumen	1
centriole	1
microtubule	1
cilium	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

1620 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUBGCP2	TUBGCP3	Q96CW5	993
TUBGCP2	TUBGCP4	Q9UGJ1	927
TUBGCP2	TUBGCP5	Q96RT8	922
TUBGCP2	TUBG1	P23258	884
TUBGCP2	TUBGCP6	Q96RT7	866
TUBGCP2	ERC2	O15083	796
TUBGCP2	MZT1	Q08AG7	763
TUBGCP2	TUBG2	Q9NRH3	760
TUBGCP2	PCNT	O95613	613
TUBGCP2	CKAP5	Q14008	570
TUBGCP2	NEDD1	Q8NHV4	570
TUBGCP2	ASRGL1	Q7L266	562
TUBGCP2	CDK5RAP2	Q96SN8	523
TUBGCP2	SFI1	A8K8P3	501
TUBGCP2	KATNB1	Q9BVA0	488

IntAct

176 interactions, top by confidence:

A	B	Type	Score
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
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TUBG2	TUBGCP3	psi-mi:“MI:0914”(association)	0.640
	PMPCB	psi-mi:“MI:0914”(association)	0.640
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
Mzt2	TUBG1	psi-mi:“MI:0914”(association)	0.560
TUBGCP2	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560
AKAP9	GOLGA2	psi-mi:“MI:0914”(association)	0.540
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
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 (280): TUBGCP2 (Affinity Capture-MS), TUBGCP2 (Affinity Capture-MS), TUBGCP2 (Affinity Capture-MS), TUBGCP2 (Affinity Capture-MS), TUBGCP2 (Affinity Capture-MS), TUBGCP2 (Affinity Capture-MS), MZT2B (Co-fractionation), TUBGCP2 (Co-fractionation), TUBGCP6 (Co-fractionation), TUBGCP2 (Affinity Capture-MS), TUBGCP2 (Proximity Label-MS), TUBGCP2 (Proximity Label-MS), TUBGCP2 (Proximity Label-MS), LGALS3BP (Affinity Capture-MS), RAD51 (Affinity Capture-MS)

ESM2 similar proteins: A1Z7T0, A2A5R2, B0W2R4, B0W3L6, B3MIV9, B3NPV7, B3NU20, B4GAM2, B4GZ20, B4HST0, B4J789, B4JW98, B4JXV2, B4KT51, B4LQ24, B4NKI9, B4P6P6, B4Q068, B4QHH0, C4A0D9, D3YXJ0, D4A631, G3X9K3, G5EGS5, O46382, P16258, P22059, Q17N72, Q24574, Q291J4, Q29B63, Q29EP6, Q2HVD6, Q39238, Q5R5J6, Q64398, Q7K4H4, Q7K5N4, Q7Q2B7, Q7TSU1

Diamond homologs: Q5R5J6, Q921G8, Q95ZG3, Q9BSJ2, Q9C5H9, Q9XYP7, Q9Y705

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TUBGCP2	“form complex”	“g-TuRC complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 200 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	18	19.0×	1e-15
Centrosome maturation	9	17.7×	1e-07
Recruitment of NuMA to mitotic centrosomes	18	16.3×	9e-15
Loss of Nlp from mitotic centrosomes	11	13.5×	6e-08
Loss of proteins required for interphase microtubule organization from the centrosome	11	13.5×	6e-08
AURKA Activation by TPX2	11	13.0×	8e-08
Regulation of PLK1 Activity at G2/M Transition	13	12.8×	5e-09
Transport of vitamins, nucleosides, and related molecules	6	12.7×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
microtubule nucleation	11	39.7×	1e-12
spindle assembly	5	12.8×	7e-03
cytoplasmic microtubule organization	6	11.9×	4e-03
mitotic spindle organization	6	9.4×	7e-03
phospholipase C-activating G protein-coupled receptor signaling pathway	9	6.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	142
Likely benign	44
Benign	9

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
691862	NM_006659.4(TUBGCP2):c.2025-2A>G	Pathogenic

SpliceAI

5004 predictions. Top by Δscore:

Variant	Effect	Δscore
10:133281432:AGGTG:A	acceptor_gain	1.0000
10:133281433:GGTG:G	acceptor_gain	1.0000
10:133281434:GTG:G	acceptor_gain	1.0000
10:133281435:TG:T	acceptor_gain	1.0000
10:133281435:TGCTG:T	acceptor_loss	1.0000
10:133281436:GCTGG:G	acceptor_loss	1.0000
10:133281437:C:CC	acceptor_gain	1.0000
10:133281438:T:A	acceptor_loss	1.0000
10:133282218:CGCA:C	donor_loss	1.0000
10:133282219:GCA:G	donor_loss	1.0000
10:133282220:CA:C	donor_loss	1.0000
10:133282221:A:AG	donor_loss	1.0000
10:133282225:T:A	donor_gain	1.0000
10:133282338:AATTT:A	acceptor_gain	1.0000
10:133282339:ATTT:A	acceptor_gain	1.0000
10:133282340:TTT:T	acceptor_gain	1.0000
10:133282341:TT:T	acceptor_gain	1.0000
10:133282343:C:CC	acceptor_gain	1.0000
10:133282358:C:CT	acceptor_gain	1.0000
10:133282676:AGACC:A	donor_gain	1.0000
10:133283074:GCACC:G	donor_loss	1.0000
10:133283075:CACC:C	donor_loss	1.0000
10:133283077:C:CG	donor_loss	1.0000
10:133283880:A:AC	donor_gain	1.0000
10:133283881:C:CC	donor_gain	1.0000
10:133283881:CG:C	donor_gain	1.0000
10:133283881:CGG:C	donor_gain	1.0000
10:133283881:CGGA:C	donor_gain	1.0000
10:133285084:CCA:C	donor_gain	1.0000
10:133285624:TCGAT:T	acceptor_gain	1.0000

AlphaMissense

5953 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:133285181:C:A	R643M	1.000
10:133289900:C:A	W428C	1.000
10:133289900:C:G	W428C	1.000
10:133292533:A:G	W394R	1.000
10:133292533:A:T	W394R	1.000
10:133281348:A:G	L833P	0.999
10:133283151:A:G	L739P	0.999
10:133285145:A:G	L655P	0.999
10:133285181:C:G	R643T	0.999
10:133285477:G:T	P625H	0.999
10:133285478:G:A	P625S	0.999
10:133285479:C:A	W624C	0.999
10:133285479:C:G	W624C	0.999
10:133285481:A:G	W624R	0.999
10:133285481:A:T	W624R	0.999
10:133285594:A:G	L586P	0.999
10:133288165:G:C	S562R	0.999
10:133288165:G:T	S562R	0.999
10:133288167:T:G	S562R	0.999
10:133288897:G:T	A495D	0.999
10:133289011:A:G	L457P	0.999
10:133289020:C:A	G454V	0.999
10:133289020:C:T	G454E	0.999
10:133289824:C:G	G454R	0.999
10:133289824:C:T	G454R	0.999
10:133289865:G:T	P440Q	0.999
10:133289902:A:G	W428R	0.999
10:133289902:A:T	W428R	0.999
10:133289958:A:T	V409D	0.999
10:133292520:C:A	G398V	0.999

dbSNP variants (sampled 300 via entrez): RS1000047859 (10:133296540 C>T), RS1000159270 (10:133306501 C>G), RS1000171726 (10:133279271 T>G), RS1000224788 (10:133287913 A>C), RS1000272386 (10:133301358 T>C), RS1000340677 (10:133298189 G>A), RS1000341421 (10:133310463 G>A), RS1000442113 (10:133306228 G>A), RS1000476327 (10:133301618 T>C), RS1000476771 (10:133298536 C>A), RS1000767043 (10:133283518 G>A), RS1000819998 (10:133288432 G>A), RS1000849016 (10:133301795 A>G), RS1000967750 (10:133283674 T>C,G), RS1001109928 (10:133307195 C>T)

Disease associations

OMIM: gene MIM:617817 | disease phenotypes: MIM:618737

GenCC curated gene-disease

Disease	Classification	Inheritance
pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures	Strong	Autosomal recessive

Mondo (1): pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures (MONDO:0032893)

Orphanet (0):

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000219	Thin upper lip vermilion
HP:0000253	Progressive microcephaly
HP:0000319	Smooth philtrum
HP:0000327	Hypoplasia of the maxilla
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000648	Optic atrophy
HP:0000664	Synophrys
HP:0001257	Spasticity
HP:0001302	Pachygyria
HP:0001348	Brisk reflexes
HP:0002079	Hypoplasia of the corpus callosum
HP:0002416	Subependymal cysts
HP:0003593	Infantile onset
HP:0006304	Widely-spaced incisors
HP:0008936	Axial hypotonia
HP:0011182	Interictal epileptiform activity
HP:0011800	Midface retrusion
HP:0032409	Subcortical band heterotopia
HP:0100704	Cerebral visual impairment

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003124_11	Mild influenza (H1N1) infection	1.000000e-09
GCST007250_1	Nonunion in individuals with fractures	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0009707	fractures, ununited

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724684 (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

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

pChembl	Type	Value	Unit	Molecule
7.40	Kd	40.1	nM	CHEMBL5653589
7.40	ED50	40.14	nM	CHEMBL5653589
6.82	IC50	150	nM	MOLIBRESIB
6.79	Kd	160.3	nM	CHEMBL3752910
6.79	ED50	160.4	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 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	2149685: Binding affinity to human TUBGCP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0401	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	2178634: Inhibition of TUBGCP2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.1500	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149685: Binding affinity to human TUBGCP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.1603	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases mutagenesis, increases methylation	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Diethylstilbestrol	decreases expression	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1
Volatile Organic Compounds	affects cotreatment, 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
CHEMBL5652727	Binding	Binding affinity to human TUBGCP2 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

Clinical trials (associated diseases)

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