TPGS1

Summary

TPGS1 (tubulin polyglutamylase complex subunit 1, HGNC:25058) is a protein-coding gene on chromosome 19p13.3, encoding Tubulin polyglutamylase complex subunit 1 (Q6ZTW0). Subunit of the tubulin polyglutamylase complex (TPGC).

Predicted to enable microtubule binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in sperm axoneme assembly. Predicted to act upstream of or within several processes, including adult behavior; chemical synaptic transmission; and protein polyglutamylation. Located in centrosome.

Source: NCBI Gene 91978 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_033513

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25058
Approved symbol	TPGS1
Name	tubulin polyglutamylase complex subunit 1
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	GTRGEO22, PGs1
Ensembl gene	ENSG00000141933
Ensembl biotype	protein_coding
OMIM	620709
Entrez	91978

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000359315, ENST00000588278

RefSeq mRNA: 1 — MANE Select: NM_033513 NM_033513

CCDS: CCDS42454

Canonical transcript exons

ENST00000359315 — 2 exons

Exon	Start	End
ENSE00000951304	507497	507844
ENSE00001431625	518889	519654

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 85.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.5722 / max 169.2802, expressed in 1805 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172681	16.5722	1805

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	85.53	gold quality
mucosa of stomach	UBERON:0001199	85.11	gold quality
leukocyte	CL:0000738	85.04	gold quality
metanephros cortex	UBERON:0010533	84.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.55	gold quality
ascending aorta	UBERON:0001496	84.15	gold quality
thoracic aorta	UBERON:0001515	84.12	gold quality
tibial artery	UBERON:0007610	83.86	gold quality
popliteal artery	UBERON:0002250	83.85	gold quality
apex of heart	UBERON:0002098	83.81	gold quality
aorta	UBERON:0000947	83.76	gold quality
left coronary artery	UBERON:0001626	83.53	gold quality
mucosa of transverse colon	UBERON:0004991	83.51	gold quality
right adrenal gland	UBERON:0001233	83.46	gold quality
left adrenal gland cortex	UBERON:0035825	83.45	gold quality
anterior cingulate cortex	UBERON:0009835	83.34	gold quality
left adrenal gland	UBERON:0001234	83.30	gold quality
descending thoracic aorta	UBERON:0002345	83.27	gold quality
right adrenal gland cortex	UBERON:0035827	83.24	gold quality
endocervix	UBERON:0000458	82.96	gold quality
granulocyte	CL:0000094	82.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.54	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.52	gold quality
ectocervix	UBERON:0012249	82.51	gold quality
right frontal lobe	UBERON:0002810	82.50	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.23	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.90	gold quality
lower esophagus	UBERON:0013473	81.88	gold quality
body of uterus	UBERON:0009853	81.86	gold quality
body of stomach	UBERON:0001161	81.56	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	1841.15
E-CURD-79	yes	1830.37
E-MTAB-8142	yes	100.62
E-CURD-88	yes	43.04
E-HCAD-1	yes	38.17
E-MTAB-6701	yes	29.98
E-GEOD-135922	yes	25.71
E-HCAD-10	yes	8.19
E-ANND-3	yes	3.59
E-GEOD-137537	no	2558.76
E-HCAD-8	no	793.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

2 targeting TPGS1, 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-6783-3P	99.89	67.92	2059
HSA-MIR-1207-5P	99.49	69.11	2983

Literature-anchored findings (GeneRIF, showing 1)

• Isolation and functional characterization of the mouse PGs1 ortholog, and comparison to the human protein. (PMID:12972506)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tpgs1	ENSDARG00000027547
mus_musculus	Tpgs1	ENSMUSG00000020308
rattus_norvegicus	Tpgs1	ENSRNOG00000008296

Protein

Protein identifiers

Tubulin polyglutamylase complex subunit 1 — Q6ZTW0 (reviewed: Q6ZTW0)

All UniProt accessions (1): Q6ZTW0

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of the tubulin polyglutamylase complex (TPGC). The complex mediates cilia and flagella polyglutamylation which is essential for their biogenesis and motility. May act in the targeting of the tubulin polyglutamylase complex. Required for the development of the spermatid flagellum.

Subunit / interactions. Part of the neuronal tubulin polyglutamylase complex which contains TPGS1, TPGS2, TTLL1, LRRC49 and NICN1. Interacts with PCM1, CSTPP1 and LRRC49.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Flagellum axoneme. Cilium basal body. Flagellum basal body. Cell projection. Axon. Dendrite. Microtubule organizing center. Centrosome. Centriolar satellite.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZTW0-1	1	yes
Q6ZTW0-2	2

RefSeq proteins (1): NP_277048* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039235	TPGS1	Family
IPR047502	DD_TPGS1	Domain
IPR057632	TPGS1_C	Domain

Pfam: PF24480

UniProt features (5 total): modified residue 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZTW0-F1	81.46	0.50

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, 266

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin

MSigDB gene sets: 314 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_BEHAVIOR, GOBP_VESICLE_LOCALIZATION, GOBP_ADULT_BEHAVIOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CELL_CELL_SIGNALING, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GGAANCGGAANY_UNKNOWN

GO Biological Process (10): chemical synaptic transmission (GO:0007268), sperm axoneme assembly (GO:0007288), adult behavior (GO:0030534), vesicle localization (GO:0051648), microtubule cytoskeleton organization (GO:0000226), spermatogenesis (GO:0007283), protein polyglutamylation (GO:0018095), cell differentiation (GO:0030154), microtubule polymerization (GO:0046785), cilium disassembly (GO:0061523)

GO Molecular Function (3): microtubule binding (GO:0008017), tubulin-glutamic acid ligase activity (GO:0070740), tubulin binding (GO:0015631)

GO Cellular Component (13): centrosome (GO:0005813), microtubule organizing center (GO:0005815), microtubule (GO:0005874), axoneme (GO:0005930), axon (GO:0030424), dendrite (GO:0030425), centriolar satellite (GO:0034451), synapse (GO:0045202), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
developmental process involved in reproduction	2
microtubule cytoskeleton	2
neuron projection	2
anterograde trans-synaptic signaling	1
axoneme assembly	1
sperm flagellum assembly	1
behavior	1
organelle localization	1
cytoskeleton organization	1
microtubule-based process	1
male gamete generation	1
peptidyl-glutamic acid modification	1
cellular developmental process	1
microtubule nucleation	1
microtubule polymerization or depolymerization	1
protein polymerization	1
supramolecular fiber organization	1
cilium organization	1
organelle disassembly	1
tubulin binding	1
protein-glutamic acid ligase activity	1
cytoskeletal protein binding	1
centriole	1
microtubule organizing center	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
dendritic tree	1
centrosome	1
cell junction	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPGS1	LRRC49	Q8IUZ0	732
TPGS1	REX1BD	Q96EN9	625
TPGS1	TTC13	Q8NBP0	575
TPGS1	CATIP	Q7Z7H3	572
TPGS1	OR4K15	Q8NH41	564
TPGS1	TEX55	Q96M34	527
TPGS1	CIMAP1D	Q3SX64	506
TPGS1	FBXL13	Q8NEE6	505
TPGS1	AK8	Q96MA6	504
TPGS1	CCDC177	Q9NQR7	493
TPGS1	GPRIN1	Q7Z2K8	487
TPGS1	EFCAB10	A6NFE3	448
TPGS1	A0A0G2JP48	A0A0G2JP48	446
TPGS1	R3HDM4	Q96D70	433
TPGS1	TPGS2	Q68CL5	410

IntAct

47 interactions, top by confidence:

A	B	Type	Score
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
EIF3F	EIF3CL	psi-mi:“MI:0914”(association)	0.640
NICN1	TTLL1	psi-mi:“MI:0914”(association)	0.640
TTLL1	CDC27	psi-mi:“MI:0914”(association)	0.640
LRRC49	EIF3F	psi-mi:“MI:0914”(association)	0.640
LRRC49	SNAP29	psi-mi:“MI:0914”(association)	0.530
ANO4	ANO6	psi-mi:“MI:0914”(association)	0.530
ANP32E	KPNA6	psi-mi:“MI:0914”(association)	0.530
GSK3B	SEC16A	psi-mi:“MI:2364”(proximity)	0.420
PCM1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
LRRC49	PCM1	psi-mi:“MI:0914”(association)	0.350
SMG8	HSP90AA4P	psi-mi:“MI:0914”(association)	0.350
ROS1	ODAD3	psi-mi:“MI:0914”(association)	0.350
TPGS1	PPFIA3	psi-mi:“MI:0914”(association)	0.350
TPGS1	PIK3R2	psi-mi:“MI:0914”(association)	0.350
CSTPP1	PEX5	psi-mi:“MI:0914”(association)	0.350
TTLL1	CAMK2B	psi-mi:“MI:0914”(association)	0.350
CSTPP1	KRBA1	psi-mi:“MI:0914”(association)	0.350
NICN1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TTLL1	RGS12	psi-mi:“MI:0914”(association)	0.350
CEP290	ARPC3	psi-mi:“MI:2364”(proximity)	0.270
KIAA0753	DVL1	psi-mi:“MI:2364”(proximity)	0.270
CEP128	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
SSX2IP	CCDC85C	psi-mi:“MI:2364”(proximity)	0.270
PCM1	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
STIL	ERVK3-1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (104): TPGS1 (Affinity Capture-MS), TPGS1 (Affinity Capture-MS), TPGS1 (Proximity Label-MS), TPGS1 (Affinity Capture-MS), TPGS1 (Proximity Label-MS), TPGS1 (Proximity Label-MS), TPGS1 (Proximity Label-MS), TPGS1 (Proximity Label-MS), TPGS1 (Proximity Label-MS), TPGS1 (Proximity Label-MS), TPGS1 (Proximity Label-MS), TPGS1 (Proximity Label-MS), TPGS1 (Proximity Label-MS), TPGS1 (Proximity Label-MS), TPGS1 (Proximity Label-MS)

ESM2 similar proteins: A5PJU7, A8MQ27, F1MLB4, F1MX48, F1SAM7, I3L5V6, O75425, O95382, P36916, Q08DG4, Q0MW30, Q14451, Q2YD98, Q32P44, Q3MIP1, Q3T033, Q3UPE3, Q3UV16, Q505F5, Q5EBM0, Q5U651, Q5ZM20, Q641Q3, Q6MG06, Q6SZW1, Q6ZTW0, Q7T0L4, Q8BGG6, Q8BH83, Q8C0R7, Q8K0Y7, Q8N9W5, Q8R2K4, Q8TE68, Q8VC03, Q96BM1, Q96E14, Q96EF6, Q96EY9, Q99JB7

Diamond homologs: Q6ZTW0, Q99MS8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TPGS1	“form complex”	“Tubulin polyglutamylase complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 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
Loss of Nlp from mitotic centrosomes	5	18.9×	8e-04
Loss of proteins required for interphase microtubule organization from the centrosome	5	18.9×	8e-04
AURKA Activation by TPX2	5	18.1×	8e-04
Recruitment of mitotic centrosome proteins and complexes	5	16.2×	1e-03
Anchoring of the basal body to the plasma membrane	6	16.1×	7e-04
Regulation of PLK1 Activity at G2/M Transition	5	15.1×	1e-03
Recruitment of NuMA to mitotic centrosomes	5	13.9×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	5	65.4×	6e-06
cilium assembly	8	10.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3751 predictions. Top by Δscore:

Variant	Effect	Δscore
17:78378805:GGAG:G	donor_gain	1.0000
17:78378806:G:GT	donor_gain	1.0000
17:78378806:GAGGT:G	donor_loss	1.0000
17:78378809:GTGA:G	donor_loss	1.0000
17:78378810:T:G	donor_loss	1.0000
17:78398246:T:TA	acceptor_gain	1.0000
17:78398247:GGTA:G	acceptor_loss	1.0000
17:78398249:TAGGT:T	acceptor_loss	1.0000
17:78398250:A:T	acceptor_loss	1.0000
17:78398350:AGGT:A	donor_loss	1.0000
17:78398352:G:C	donor_loss	1.0000
17:78399341:T:TA	acceptor_gain	1.0000
17:78399345:CAGGC:C	acceptor_loss	1.0000
17:78399534:GCGG:G	donor_gain	1.0000
17:78399536:GG:G	donor_gain	1.0000
17:78399537:GG:G	donor_gain	1.0000
17:78399538:G:C	donor_loss	1.0000
17:78399538:G:GG	donor_gain	1.0000
17:78399539:T:G	donor_loss	1.0000
17:78400672:TGTAG:T	acceptor_loss	1.0000
17:78400673:GTA:G	acceptor_loss	1.0000
17:78400674:TA:T	acceptor_loss	1.0000
17:78400675:A:AG	acceptor_gain	1.0000
17:78400675:A:C	acceptor_loss	1.0000
17:78400675:AGT:A	acceptor_gain	1.0000
17:78400676:G:GC	acceptor_gain	1.0000
17:78400676:GT:G	acceptor_gain	1.0000
17:78400676:GTG:G	acceptor_gain	1.0000
17:78400676:GTGC:G	acceptor_gain	1.0000
17:78400676:GTGCA:G	acceptor_gain	1.0000

AlphaMissense

1839 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:519092:T:C	F181S	0.998
19:519371:T:C	F274S	0.998
19:507702:T:C	F66L	0.997
19:507704:C:A	F66L	0.997
19:507704:C:G	F66L	0.997
19:518896:T:C	F116L	0.997
19:518898:C:A	F116L	0.997
19:518898:C:G	F116L	0.997
19:518969:G:A	G140E	0.997
19:507820:T:A	L105H	0.996
19:518897:T:C	F116S	0.996
19:518977:T:G	Y143D	0.996
19:519395:T:C	F282S	0.996
19:507718:T:C	F71S	0.995
19:518918:C:A	A123D	0.995
19:518968:G:T	G140W	0.995
19:518969:G:T	G140V	0.995
19:519091:T:C	F181L	0.995
19:519093:C:A	F181L	0.995
19:519093:C:G	F181L	0.995
19:519130:T:C	F194L	0.995
19:519132:C:A	F194L	0.995
19:519132:C:G	F194L	0.995
19:507658:C:A	A51D	0.994
19:518920:T:G	Y124D	0.994
19:518987:T:C	L146P	0.994
19:518990:T:A	L147H	0.994
19:519077:T:A	V176E	0.994
19:519370:T:C	F274L	0.994
19:519372:T:A	F274L	0.994

dbSNP variants (sampled 300 via entrez): RS1000152843 (19:514582 A>C), RS1000265907 (19:509353 C>A), RS1000573842 (19:506260 A>C), RS1000762902 (19:509165 G>A), RS1000809319 (19:511682 G>A), RS1001068920 (19:506860 G>A,C), RS1001142567 (19:510851 T>G), RS1001167162 (19:515413 A>G), RS1001193143 (19:510738 T>C), RS1001198199 (19:515093 C>A,T), RS1001336195 (19:506921 T>C,G), RS1001383057 (19:510556 G>A,T), RS1001450528 (19:510905 A>T), RS1002288060 (19:507127 T>A), RS1002424299 (19:506993 T>C)

Disease associations

OMIM: gene MIM:620709 | 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
GCST90002396_3	Mean reticulocyte volume	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
fluorene-9-bisphenol	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic	increases methylation	1
Cisplatin	increases expression, affects cotreatment	1
Estradiol	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Palmitic Acid	decreases expression	1

Clinical trials (associated diseases)

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