TPPP2

Summary

TPPP2 (tubulin polymerization promoting protein family member 2, HGNC:19293) is a protein-coding gene on chromosome 14q11.2, encoding Tubulin polymerization-promoting protein family member 2 (P59282). Probable regulator of microtubule dynamics required for sperm motility.

Enables tubulin binding activity. Involved in regulation of flagellated sperm motility. Located in cytosol.

Source: NCBI Gene 122664 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_173846

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19293
Approved symbol	TPPP2
Name	tubulin polymerization promoting protein family member 2
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	p25beta, p18, CT152
Ensembl gene	ENSG00000179636
Ensembl biotype	protein_coding
OMIM	616956
Entrez	122664

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000321760, ENST00000460647, ENST00000472458, ENST00000481535, ENST00000495665, ENST00000525425, ENST00000529496, ENST00000530140, ENST00000532060, ENST00000533755, ENST00000534434, ENST00000555751

RefSeq mRNA: 1 — MANE Select: NM_173846 NM_173846

CCDS: CCDS9566

Canonical transcript exons

ENST00000321760 — 4 exons

Exon	Start	End
ENSE00001296940	21031012	21031165
ENSE00001851632	21031892	21032815
ENSE00001914024	21030217	21030304
ENSE00002023465	21030513	21030754

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 99.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3460 / max 367.1832, expressed in 7 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138496	0.3141	7
138495	0.0252	3
138497	0.0067	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.31	gold quality
left testis	UBERON:0004533	98.67	gold quality
right testis	UBERON:0004534	98.40	gold quality
adult organism	UBERON:0007023	95.84	gold quality
testis	UBERON:0000473	95.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.25	gold quality
right lobe of liver	UBERON:0001114	84.89	gold quality
liver	UBERON:0002107	77.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.69	gold quality
gastrocnemius	UBERON:0001388	73.58	gold quality
muscle of leg	UBERON:0001383	72.80	gold quality
ventricular zone	UBERON:0003053	66.87	gold quality
cauda epididymis	UBERON:0004360	65.46	gold quality
skeletal muscle tissue	UBERON:0001134	64.51	gold quality
mucosa of transverse colon	UBERON:0004991	64.44	gold quality
vena cava	UBERON:0004087	64.17	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	63.92	gold quality
tendon of biceps brachii	UBERON:0008188	63.32	gold quality
right ovary	UBERON:0002118	63.09	gold quality
left ovary	UBERON:0002119	62.99	gold quality
buccal mucosa cell	CL:0002336	62.78	gold quality
deltoid	UBERON:0001476	62.11	gold quality
tibialis anterior	UBERON:0001385	61.93	silver quality
muscle tissue	UBERON:0002385	61.80	gold quality
adult mammalian kidney	UBERON:0000082	61.37	gold quality
heart left ventricle	UBERON:0002084	60.99	gold quality
quadriceps femoris	UBERON:0001377	60.91	gold quality
saliva-secreting gland	UBERON:0001044	60.67	gold quality
parotid gland	UBERON:0001831	60.63	gold quality
cardiac ventricle	UBERON:0002082	60.47	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	3809.48
E-ANND-3	no	1.12

Regulation

Is transcription factor: no

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tppp2	ENSDARG00000035338
mus_musculus	Tppp2	ENSMUSG00000008813
rattus_norvegicus		ENSRNOG00000090962
drosophila_melanogaster	ringer	FBGN0266417
caenorhabditis_elegans	tppp-1	WBGENE00016321

Paralogs (2): TPPP3 (ENSG00000159713), TPPP (ENSG00000171368)

Protein

Protein identifiers

Tubulin polymerization-promoting protein family member 2 — P59282 (reviewed: P59282)

Alternative names: Protein p25-beta, TPPP/p18

All UniProt accessions (6): P59282, D6R9S2, D6RIC1, H0Y8L2, H0YEZ3, H0YJP6

UniProt curated annotations — full annotation on UniProt →

Function. Probable regulator of microtubule dynamics required for sperm motility. In contrast to other members of the family, has no microtubule bundling activity.

Subunit / interactions. Interacts with CFAP65.

Subcellular location. Cytoplasm. Cytosol. Cell projection. Cilium. Flagellum.

Tissue specificity. Expressed in spermatids. Detected in liver cancer (at protein level).

Similarity. Belongs to the TPPP family.

RefSeq proteins (1): NP_776245* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF05517

UniProt features (4 total): chain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59282-F1	85.45	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, TGACATY_UNKNOWN, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY

GO Biological Process (5): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), positive regulation of protein polymerization (GO:0032273), microtubule polymerization (GO:0046785), regulation of flagellated sperm motility (GO:1901317)

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

GO Cellular Component (7): cytosol (GO:0005829), sperm flagellum (GO:0036126), cytoplasm (GO:0005737), microtubule (GO:0005874), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein polymerization	2
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
positive regulation of protein-containing complex assembly	1
regulation of protein polymerization	1
microtubule nucleation	1
microtubule polymerization or depolymerization	1
supramolecular fiber organization	1
flagellated sperm motility	1
regulation of cilium movement involved in cell motility	1
regulation of reproductive process	1
cytoskeletal protein binding	1
cytoplasm	1
9+2 motile cilium	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

560 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPPP2	OAZ3	Q9UMX2	566
TPPP2	SPACA1	Q9HBV2	535
TPPP2	ZPBP	Q9BS86	514
TPPP2	TMPRSS12	Q86WS5	507
TPPP2	RSPH1	Q8WYR4	483
TPPP2	PRSS55	Q6UWB4	480
TPPP2	NTN3	O00634	421
TPPP2	GARIN5A	Q6IPT2	421
TPPP2	NME8	Q8N427	415
TPPP2	GEMIN4	P57678	414
TPPP2	SLIT3	O75094	402
TPPP2	HSPB9	Q9BQS6	401
TPPP2	TMT1A	Q9H8H3	380
TPPP2	TEX38	Q6PEX7	377
TPPP2	PPP2R2B	Q00005	373

IntAct

9 interactions, top by confidence:

A	B	Type	Score
MYL6	MYL6B	psi-mi:“MI:0914”(association)	0.530
ENSA	TPPP2	psi-mi:“MI:0915”(physical association)	0.400
C11orf71	TPPP2	psi-mi:“MI:0915”(physical association)	0.400
TPPP2	BTBD1	psi-mi:“MI:0915”(physical association)	0.400
MT1M	PGP	psi-mi:“MI:0914”(association)	0.350
CMTM8	UBXN8	psi-mi:“MI:0914”(association)	0.350
CST9L	QSOX1	psi-mi:“MI:0914”(association)	0.350
NDP	PLXNA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): TPPP2 (Positive Genetic), TPPP2 (Affinity Capture-MS), TPPP2 (Affinity Capture-MS), BTBD1 (Affinity Capture-MS), TPPP2 (Affinity Capture-MS), TPPP2 (Affinity Capture-MS), TPPP2 (Affinity Capture-MS), TPPP2 (Affinity Capture-MS), TPPP2 (Affinity Capture-MS), TPPP2 (PCA), TPPP2 (PCA)

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1272 predictions. Top by Δscore:

Variant	Effect	Δscore
14:21025653:C:CA	donor_gain	1.0000
14:21030750:GTCAA:G	donor_gain	1.0000
14:21030755:G:GG	donor_gain	1.0000
14:21031162:TACT:T	donor_gain	1.0000
14:21031163:ACT:A	donor_gain	1.0000
14:21031163:ACTGT:A	donor_loss	1.0000
14:21031165:TGTG:T	donor_loss	1.0000
14:21031166:G:GG	donor_gain	1.0000
14:21031167:T:A	donor_loss	1.0000
14:21031168:GAGT:G	donor_loss	1.0000
14:21025680:T:A	donor_gain	0.9900
14:21031005:T:A	acceptor_gain	0.9900
14:21031161:CTACT:C	donor_gain	0.9900
14:21031164:CT:C	donor_gain	0.9900
14:21031890:A:AG	acceptor_gain	0.9900
14:21031891:G:GG	acceptor_gain	0.9900
14:21031891:GAAA:G	acceptor_gain	0.9900
14:21025344:AGC:A	donor_gain	0.9800
14:21025578:G:A	donor_gain	0.9800
14:21025654:C:A	donor_gain	0.9800
14:21025668:T:TA	donor_gain	0.9800
14:21025676:CCT:C	donor_gain	0.9800
14:21025678:T:TA	donor_gain	0.9800
14:21030726:G:GT	donor_gain	0.9800
14:21030751:TC:T	donor_gain	0.9800
14:21024598:AGTCT:A	donor_gain	0.9700
14:21025422:T:TA	donor_gain	0.9700
14:21025480:TGA:T	donor_gain	0.9700
14:21031002:A:AG	acceptor_gain	0.9700
14:21031886:TTGCA:T	acceptor_loss	0.9700

AlphaMissense

1126 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:21030741:T:C	F54L	0.998
14:21030743:C:A	F54L	0.998
14:21030743:C:G	F54L	0.998
14:21030615:T:C	F12L	0.997
14:21030617:T:A	F12L	0.997
14:21030617:T:G	F12L	0.997
14:21031055:G:C	A73P	0.997
14:21031964:T:C	F134L	0.997
14:21031966:T:A	F134L	0.997
14:21031966:T:G	F134L	0.997
14:21030681:T:C	C34R	0.996
14:21030732:G:C	D51H	0.996
14:21030606:T:C	F9L	0.995
14:21030608:C:A	F9L	0.995
14:21030608:C:G	F9L	0.995
14:21030715:T:A	V45D	0.995
14:21030675:A:G	K32E	0.994
14:21030677:G:C	K32N	0.994
14:21030677:G:T	K32N	0.994
14:21030742:T:C	F54S	0.994
14:21031923:T:C	L120S	0.994
14:21031940:T:G	Y126D	0.994
14:21030733:A:T	D51V	0.993
14:21031941:A:C	Y126S	0.993
14:21031961:C:A	R133S	0.993
14:21030679:T:C	L33P	0.992
14:21031965:T:C	F134S	0.992
14:21031056:C:A	A73E	0.991
14:21031940:T:C	Y126H	0.991
14:21031947:G:A	G128D	0.991

dbSNP variants (sampled 300 via entrez): RS1000119394 (14:21032810 G>A), RS1000975098 (14:21022765 G>A,C,T), RS1001034548 (14:21030196 C>T), RS1001107937 (14:21030029 G>A,T), RS1001457179 (14:21024285 T>C,G), RS1001553627 (14:21029594 A>G,T), RS1001783881 (14:21024597 C>A,G), RS1001975577 (14:21024282 A>G), RS1002122201 (14:21035193 T>C), RS1002168055 (14:21034465 A>ACCAG), RS1002386495 (14:21025485 C>G,T), RS1002486302 (14:21025126 C>A,G,T), RS1002849079 (14:21030090 G>A), RS1002853027 (14:21025407 T>C,G), RS1002946334 (14:21025241 G>T)

Disease associations

OMIM: gene MIM:616956 | 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
GCST008156_144	Hip circumference adjusted for BMI	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
fluorene-9-bisphenol	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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