TPPP3

Summary

TPPP3 (tubulin polymerization promoting protein family member 3, HGNC:24162) is a protein-coding gene on chromosome 16q22.1, encoding Tubulin polymerization-promoting protein family member 3 (Q9BW30). Regulator of microtubule dynamic that has microtubule bundling activity.

Enables tubulin binding activity. Involved in decidualization and microtubule bundle formation. Located in microtubule bundle and perinuclear region of cytoplasm.

Source: NCBI Gene 51673 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_015964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24162
Approved symbol	TPPP3
Name	tubulin polymerization promoting protein family member 3
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CGI-38, p25gamma, p20
Ensembl gene	ENSG00000159713
Ensembl biotype	protein_coding
OMIM	616957
Entrez	51673

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000290942, ENST00000393957, ENST00000561537, ENST00000562206, ENST00000564104, ENST00000874010, ENST00000874011, ENST00000874012, ENST00000874013, ENST00000948412, ENST00000948413

RefSeq mRNA: 2 — MANE Select: NM_015964 NM_015964, NM_016140

CCDS: CCDS10835

Canonical transcript exons

ENST00000393957 — 4 exons

Exon	Start	End
ENSE00001138079	67393380	67393498
ENSE00001272797	67390479	67390632
ENSE00001272841	67390924	67391117
ENSE00001380168	67389809	67390362

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 99.93.

FANTOM5 (CAGE): breadth broad, TPM avg 8.3013 / max 994.8659, expressed in 599 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157771	7.9302	597
157767	0.2625	66
157768	0.0772	50
157766	0.0314	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.95	gold quality
hypothalamus	UBERON:0001898	98.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.74	gold quality
corpus callosum	UBERON:0002336	98.21	gold quality
substantia nigra	UBERON:0002038	98.13	gold quality
amygdala	UBERON:0001876	98.09	gold quality
temporal lobe	UBERON:0001871	98.08	gold quality
Ammon’s horn	UBERON:0001954	98.03	gold quality
fallopian tube	UBERON:0003889	97.33	gold quality
putamen	UBERON:0001874	97.11	gold quality
skin of leg	UBERON:0001511	96.65	gold quality
anterior cingulate cortex	UBERON:0009835	96.63	gold quality
zone of skin	UBERON:0000014	96.54	gold quality
caudate nucleus	UBERON:0001873	96.54	gold quality
placenta	UBERON:0001987	96.52	gold quality
skin of abdomen	UBERON:0001416	96.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.81	gold quality
primary visual cortex	UBERON:0002436	95.78	gold quality
right lung	UBERON:0002167	95.33	gold quality
right frontal lobe	UBERON:0002810	94.83	gold quality
apex of heart	UBERON:0002098	94.03	gold quality
nucleus accumbens	UBERON:0001882	94.00	gold quality
left uterine tube	UBERON:0001303	93.99	gold quality
cerebral cortex	UBERON:0000956	93.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.68	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.59	gold quality
lower esophagus	UBERON:0013473	93.49	gold quality
right atrium auricular region	UBERON:0006631	93.44	gold quality

Single-cell (SCXA)

Detected in 29 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	5127.89
E-MTAB-10287	yes	4757.76
E-HCAD-1	yes	4684.29
E-MTAB-10283	yes	4523.18
E-MTAB-6653	yes	4330.56
E-GEOD-124472	yes	4285.95
E-GEOD-130148	yes	3036.27
E-MTAB-6701	yes	2770.05
E-CURD-114	yes	2714.02
E-HCAD-15	yes	2497.07
E-MTAB-6308	yes	2333.34
E-MTAB-9154	yes	1976.45
E-MTAB-10662	yes	1712.45
E-CURD-122	yes	1412.89
E-HCAD-38	yes	1390.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting TPPP3, 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-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-1263	98.13	69.18	459
HSA-MIR-4423-3P	97.98	69.66	912
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-588	96.45	68.36	1127

Literature-anchored findings (GeneRIF, showing 11)

• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• TPPP3 played a crucial role in cell mitosis by regulating centrosomes amplification and/or spindles translocation processes. (PMID:19633818)
• TPPP3 overexpression enhanced cell proliferation, migration and invasion and regulated the expression of Twist1, suggesting that aberrant expression of TPPP3 could induce a more metastatic phenotype in non-small-cell lung carcinoma. (PMID:30404076)
• Data suggest that tubulin polymerization-promoting protein family member 3 (TPPP3) plays a significant role in decidualization. (PMID:30667362)
• Silence of TPPP3 suppresses cell proliferation, invasion and migration via inactivating NF-kappaB/COX2 signal pathway in breast cancer cell. (PMID:32515139)
• Interaction of TPPP3 with VDAC1 Promotes Endothelial Injury through Activation of Reactive Oxygen Species. (PMID:33082910)
• TPPP3 Associated with Prognosis and Immune Infiltrates in Head and Neck Squamous Carcinoma. (PMID:33083464)
• TPPP3 inhibits the proliferation, invasion and migration of endometrial carcinoma targeted with miR-1827. (PMID:33644928)
• The expression and role of tubulin polymerization-promoting protein 3 in oral squamous cell carcinoma. (PMID:36058091)
• Modulatory Role of TPPP3 in Microtubule Organization and Its Impact on Alpha-Synuclein Pathology. (PMID:36230985)
• TPPP3 promote epithelial-mesenchymal transition via Snail1 in glioblastoma. (PMID:37863960)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tppp3	ENSDARG00000030463
mus_musculus	Tppp3	ENSMUSG00000014846
rattus_norvegicus	Tppp3	ENSRNOG00000016890
drosophila_melanogaster	ringer	FBGN0266417
caenorhabditis_elegans	tppp-1	WBGENE00016321

Paralogs (2): TPPP (ENSG00000171368), TPPP2 (ENSG00000179636)

Protein

Protein identifiers

Tubulin polymerization-promoting protein family member 3 — Q9BW30 (reviewed: Q9BW30)

Alternative names: TPPP/p20

All UniProt accessions (1): Q9BW30

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of microtubule dynamic that has microtubule bundling activity. Required for embryo implantation; possibly by regulating beta-catenin. Also required for decidualization via regulation of beta-catenin.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in endometrium during the mid-secretory phase (LH + 7) (at protein level).

Similarity. Belongs to the TPPP family.

RefSeq proteins (2): NP_057048, NP_057224 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008907	TPP/p25	Family
IPR011992	EF-hand-dom_pair	Homologous_superfamily

Pfam: PF05517

UniProt features (25 total): strand 8, helix 5, sequence conflict 5, turn 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2JRF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BW30-F1	84.55	0.39

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): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 193 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, BENPORATH_ES_WITH_H3K27ME3, chr16q22, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOBP_DECIDUALIZATION, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, BOQUEST_STEM_CELL_CULTURED_VS_FRESH_DN, SMID_BREAST_CANCER_LUMINAL_B_UP, INGRAM_SHH_TARGETS_DN

GO Biological Process (5): microtubule bundle formation (GO:0001578), embryo implantation (GO:0007566), positive regulation of protein polymerization (GO:0032273), decidualization (GO:0046697), microtubule polymerization (GO:0046785)

GO Molecular Function (1): tubulin binding (GO:0015631)

GO Cellular Component (5): cytoplasm (GO:0005737), microtubule (GO:0005874), cytoskeleton (GO:0005856), perinuclear region of cytoplasm (GO:0048471), microtubule bundle (GO:0097427)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein polymerization	2
microtubule cytoskeleton organization	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
positive regulation of protein-containing complex assembly	1
regulation of protein polymerization	1
maternal placenta development	1
developmental process involved in reproduction	1
tissue development	1
microtubule nucleation	1
microtubule polymerization or depolymerization	1
supramolecular fiber organization	1
cytoskeletal protein binding	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intracellular membraneless organelle	1
cytoplasm	1
cytoskeleton	1
microtubule	1

Protein interactions and networks

STRING

814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPPP3	SCGB3A2	Q96PL1	476
TPPP3	DRC12	Q494R4	414
TPPP3	THBS3	P49746	397
TPPP3	CIMAP3	Q8TCI5	383
TPPP3	ITIH3	Q06033	379
TPPP3	CD3D	P04234	373
TPPP3	RSPH1	Q8WYR4	368
TPPP3	FOXJ1	Q92949	366
TPPP3	SFTPA2	P07714	356
TPPP3	MS4A2	Q01362	348
TPPP3	MKX	Q8IYA7	347
TPPP3	SFTPB	P07988	347
TPPP3	SERTM1	A2A2V5	341
TPPP3	MYADM	Q96S97	338
TPPP3	R3HDM4	Q96D70	332

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TPPP3	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
ZC3HC1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): ARFGAP3 (Co-fractionation), TPPP3 (Proximity Label-MS), TPPP3 (Positive Genetic), TPPP3 (Affinity Capture-MS), TPPP3 (Affinity Capture-MS), TPPP3 (Affinity Capture-MS), TPPP3 (Two-hybrid), TPPP3 (Proximity Label-MS), TPPP3 (Proximity Label-MS), TPPP3 (Proximity Label-MS), TPPP3 (Proximity Label-MS)

ESM2 similar proteins: A4IIY2, A6ZPY2, D3ZQL7, O18282, O42929, O94811, P0CR50, P0CR51, P18432, P20232, P35600, P36621, P40122, P40124, P47089, P49373, P52652, P55010, P55871, P59282, P59325, P91127, Q01518, Q07205, Q08163, Q08873, Q0P5Y3, Q27957, Q2VPM9, Q3SYV4, Q3T077, Q3ZCC8, Q4QQU6, Q4R3A0, Q4R4I6, Q54LA1, Q5PPN5, Q5R4L0, Q5R8B4, Q6CJ30

Diamond homologs: A4IIY2, B6KAS6, D3ZQL7, O94811, P59282, P91127, Q0P5Y3, Q27957, Q2VPM9, Q3T077, Q3ZCC8, Q4R3A0, Q5PPN5, Q7TQD2, Q9BW30, Q9CRB6, Q9VV43, B3NKK1, B4GXC2, B5DK35, C0H4E4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1072 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67390475:TTA:T	donor_loss	1.0000
16:67390476:TA:T	donor_loss	1.0000
16:67390477:A:AC	donor_gain	1.0000
16:67390477:A:AT	donor_loss	1.0000
16:67390478:C:CT	donor_gain	1.0000
16:67390478:CAGTG:C	donor_gain	1.0000
16:67390922:A:AC	donor_gain	1.0000
16:67390923:C:CC	donor_gain	1.0000
16:67390923:CTTGA:C	donor_gain	1.0000
16:67390359:CTTT:C	acceptor_gain	0.9900
16:67390361:TT:T	acceptor_gain	0.9900
16:67390361:TTC:T	acceptor_loss	0.9900
16:67390362:TC:T	acceptor_loss	0.9900
16:67390363:C:CG	acceptor_loss	0.9900
16:67390472:CACTT:C	donor_loss	0.9900
16:67390478:CA:C	donor_gain	0.9900
16:67390478:CAG:C	donor_gain	0.9900
16:67390506:G:A	donor_gain	0.9900
16:67390885:T:TA	donor_gain	0.9900
16:67390920:TCACT:T	donor_loss	0.9900
16:67390927:A:C	donor_gain	0.9900
16:67391113:CCACC:C	acceptor_gain	0.9900
16:67391114:CACCC:C	acceptor_gain	0.9900
16:67393034:A:AC	donor_gain	0.9900
16:67393034:ACT:A	donor_gain	0.9900
16:67393035:C:CC	donor_gain	0.9900
16:67393035:CTC:C	donor_gain	0.9900
16:67390363:C:CC	acceptor_gain	0.9800
16:67390478:CAGT:C	donor_gain	0.9800
16:67390631:CC:C	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000177730 (16:67394562 A>G), RS1000451871 (16:67392298 G>C), RS1000502765 (16:67393437 G>A,T), RS1000503652 (16:67391914 C>T), RS1000619018 (16:67393612 G>A,C), RS1002136406 (16:67393965 C>T), RS1002201084 (16:67395335 C>A,T), RS1002628426 (16:67390631 C>G,T), RS1003476333 (16:67391622 C>T), RS1004026049 (16:67389639 G>T), RS1004089116 (16:67394509 C>G,T), RS1005292131 (16:67394087 C>CG), RS1006675917 (16:67389318 G>A), RS1007803454 (16:67393659 G>A,T), RS1007919776 (16:67392688 C>G,T)

Disease associations

OMIM: gene MIM:616957 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_113	Refractive error	2.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
Air Pollutants	decreases expression, increases abundance, increases expression	3
bisphenol A	affects expression, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Smoke	increases abundance, increases expression, decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
deguelin	decreases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Cisplatin	decreases expression, affects cotreatment	1
Selenium	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1
beta-Naphthoflavone	decreases expression	1

Clinical trials (associated diseases)

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