TPGS2

Summary

TPGS2 (tubulin polyglutamylase complex subunit 2, HGNC:24561) is a protein-coding gene on chromosome 18q12.2, encoding Tubulin polyglutamylase complex subunit 2 (Q68CL5). Subunit of the tubulin polyglutamylase complex (TPGC).

This gene encodes a protein that is a component of the neuronal polyglutamylase complex, which plays a role in post-translational addition of glutamate residues to C-terminal tubulin tails. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 25941 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_015476

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24561
Approved symbol	TPGS2
Name	tubulin polyglutamylase complex subunit 2
Location	18q12.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP586M1523, HsT3006, PGs2
Ensembl gene	ENSG00000134779
Ensembl biotype	protein_coding
OMIM	620710
Entrez	25941

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 18 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron

ENST00000334295, ENST00000383056, ENST00000585635, ENST00000587129, ENST00000587207, ENST00000587382, ENST00000587511, ENST00000588909, ENST00000589049, ENST00000590258, ENST00000590337, ENST00000590500, ENST00000590652, ENST00000590692, ENST00000590842, ENST00000591648, ENST00000591823, ENST00000591906, ENST00000593035, ENST00000610723, ENST00000614939, ENST00000909158, ENST00000909159, ENST00000909160, ENST00000913990

RefSeq mRNA: 10 — MANE Select: NM_015476 NM_001271949, NM_001271950, NM_001271951, NM_001271952, NM_001271953, NM_001271954, NM_001271955, NM_001271956, NM_001330572, NM_015476

CCDS: CCDS32817, CCDS62421, CCDS62422, CCDS62423, CCDS62424, CCDS74214, CCDS74215, CCDS82248

Canonical transcript exons

ENST00000334295 — 7 exons

Exon	Start	End
ENSE00001257656	36828683	36829002
ENSE00003303372	36794108	36797050
ENSE00003458523	36800198	36800311
ENSE00003514360	36818894	36818973
ENSE00003550982	36805374	36805502
ENSE00003571312	36807847	36807934
ENSE00003713965	36798449	36798609

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.7890 / max 216.1706, expressed in 1820 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171694	26.0565	1797
171698	18.0901	1805
171697	1.5337	931
171696	0.6634	402
171699	0.6034	285
171693	0.3899	185
171695	0.3560	180
171700	0.0958	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.01	gold quality
sperm	CL:0000019	98.89	gold quality
left testis	UBERON:0004533	98.89	gold quality
right testis	UBERON:0004534	98.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.66	gold quality
ventricular zone	UBERON:0003053	98.40	gold quality
male germ cell	CL:0000015	98.24	gold quality
stromal cell of endometrium	CL:0002255	97.63	gold quality
cortical plate	UBERON:0005343	97.47	gold quality
testis	UBERON:0000473	97.34	gold quality
adult organism	UBERON:0007023	97.27	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.24	gold quality
embryo	UBERON:0000922	97.04	gold quality
prefrontal cortex	UBERON:0000451	97.00	gold quality
spinal cord	UBERON:0002240	96.66	gold quality
cingulate cortex	UBERON:0003027	96.35	gold quality
pons	UBERON:0000988	96.32	gold quality
anterior cingulate cortex	UBERON:0009835	96.32	gold quality
substantia nigra pars compacta	UBERON:0001965	96.29	gold quality
descending thoracic aorta	UBERON:0002345	96.26	gold quality
right frontal lobe	UBERON:0002810	96.19	gold quality
hypothalamus	UBERON:0001898	96.09	gold quality
substantia nigra	UBERON:0002038	95.96	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.83	gold quality
amygdala	UBERON:0001876	95.80	gold quality
thoracic aorta	UBERON:0001515	95.75	gold quality
ascending aorta	UBERON:0001496	95.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.68	gold quality
midbrain	UBERON:0001891	95.66	gold quality
mucosa of stomach	UBERON:0001199	95.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	144.96
E-CURD-122	yes	19.05
E-MTAB-6678	no	3.61
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting TPGS2, 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-8485	100.00	77.57	4731
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tpgs2	ENSDARG00000011926
mus_musculus	Tpgs2	ENSMUSG00000024269
rattus_norvegicus	Tpgs2	ENSRNOG00000054118
drosophila_melanogaster	CG6931	FBGN0036236

Protein

Protein identifiers

Tubulin polyglutamylase complex subunit 2 — Q68CL5 (reviewed: Q68CL5)

All UniProt accessions (14): A0A087WUC8, A0A087WV06, A0A087WZ07, A0A087X0Q8, Q68CL5, A0A087X1R7, K7EJA6, K7EK44, K7EKC0, K7ELA6, K7EN50, K7ENZ9, K7EP30, K7ERK3

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.

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

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q68CL5-2	2	yes
Q68CL5-1	1
Q68CL5-3	3
Q68CL5-4	4
Q68CL5-5	5

RefSeq proteins (10): NP_001258878, NP_001258879, NP_001258880, NP_001258881, NP_001258882, NP_001258883, NP_001258884, NP_001258885, NP_001317501, NP_056291* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018958	Knr4/Smi1-like_dom	Domain
IPR037883	Knr4/Smi1-like_sf	Homologous_superfamily
IPR039231	TPGS2	Family

UniProt features (10 total): splice variant 5, chain 1, region of interest 1, compositionally biased region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68CL5-F1	74.51	0.30

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 172 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, CCAWYNNGAAR_UNKNOWN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, MORF_RAD21, MITSIADES_RESPONSE_TO_APLIDIN_DN, YY1_Q6, IWANAGA_E2F1_TARGETS_INDUCED_BY_SERUM, GOCC_MICROTUBULE_ORGANIZING_CENTER, chr18q12, YY1_02, KMCATNNWGGA_UNKNOWN, GOCC_CENTROSOME, DAZARD_RESPONSE_TO_UV_SCC_UP, EGR1_01

GO Biological Process (4): microtubule cytoskeleton organization (GO:0000226), protein polyglutamylation (GO:0018095), microtubule polymerization (GO:0046785), cilium disassembly (GO:0061523)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): microtubule (GO:0005874), centriolar satellite (GO:0034451), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

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	2
cytoskeleton organization	1
microtubule-based process	1
peptidyl-glutamic acid modification	1
microtubule nucleation	1
microtubule polymerization or depolymerization	1
protein polymerization	1
supramolecular fiber organization	1
cilium organization	1
organelle disassembly	1
binding	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
centrosome	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPGS2	KIAA1328	Q86T90	714
TPGS2	SAYSD1	Q9NPB0	584
TPGS2	C5orf22	Q49AR2	562
TPGS2	TRMT13	Q9NUP7	550
TPGS2	PIGH	Q14442	502
TPGS2	TPGS1	Q6ZTW0	410
TPGS2	ANKRD40	Q6AI12	408
TPGS2	NXT2	Q9NPJ8	407
TPGS2	LRRC49	Q8IUZ0	401
TPGS2	CNPPD1	Q9BV87	397
TPGS2	NICN1	Q9BSH3	388
TPGS2	CHAMP1	Q96JM3	380
TPGS2	TYW3	Q6IPR3	376
TPGS2	UQCC5	Q8WVI0	370
TPGS2	FAM53C	Q9NYF3	357

IntAct

28 interactions, top by confidence:

A	B	Type	Score
NICN1	TTLL1	psi-mi:“MI:0914”(association)	0.640
TTLL1	CDC27	psi-mi:“MI:0914”(association)	0.640
NICN1	TPGS2	psi-mi:“MI:0914”(association)	0.640
LRRC49	EIF3F	psi-mi:“MI:0914”(association)	0.640
OTP	TPGS2	psi-mi:“MI:0915”(physical association)	0.560
LRRC49	SNAP29	psi-mi:“MI:0914”(association)	0.530
CSTPP1	TPGS2	psi-mi:“MI:0914”(association)	0.530
GRAPL	TPGS2	psi-mi:“MI:0915”(physical association)	0.400
TPGS2	RAP1B	psi-mi:“MI:0915”(physical association)	0.400
EWSR1	TPGS2	psi-mi:“MI:0915”(physical association)	0.370
TPGS2	ZMYM6	psi-mi:“MI:0914”(association)	0.350
LRRC49	PCM1	psi-mi:“MI:0914”(association)	0.350
CSTPP1	TPGS2	psi-mi:“MI:0914”(association)	0.350
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
TPGS1	PPFIA3	psi-mi:“MI:0914”(association)	0.350
CSTPP1	CRYGS	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
LRRC49	ASS1	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
TPGS2	OTP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): TPGS2 (Affinity Capture-RNA), TPGS2 (Affinity Capture-RNA), TPGS2 (Two-hybrid), TPGS2 (Affinity Capture-MS), TPGS2 (Affinity Capture-MS), TPGS2 (Two-hybrid), TPGS2 (Affinity Capture-MS), TPGS2 (Affinity Capture-MS), TPGS2 (Affinity Capture-MS), TPGS2 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), ZMYM6 (Affinity Capture-MS), ACTB (Affinity Capture-MS), UBR4 (Affinity Capture-MS), TPGS2 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A0JNW5, A2AAE1, A2AGL3, A2RSJ4, A2RT67, A2RUS2, A2RV80, B0LPN4, B1H2P5, E7F240, E9Q401, O00507, O94967, P30957, P48553, P51593, Q14161, Q2LD37, Q3TLI0, Q3UHE1, Q3UVG3, Q3UX43, Q5F361, Q5M7Q1, Q5RAQ5, Q5ZJK1, Q658Y4, Q68CL5, Q6BDS2, Q6P6Y1, Q6TEP1, Q6VNB8, Q7TMY8, Q7TSG1, Q7Z6Z7, Q8BHY8, Q8CB44, Q8CGF6

Diamond homologs: Q66JT5, Q68CL5, Q6AXS8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TPGS2	“form complex”	“Tubulin polyglutamylase complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1685 predictions. Top by Δscore:

Variant	Effect	Δscore
18:36779421:T:A	acceptor_gain	1.0000
18:36807932:CTT:C	acceptor_gain	1.0000
18:36807935:C:CC	acceptor_gain	1.0000
18:36818892:A:AC	donor_gain	1.0000
18:36818893:C:CC	donor_gain	1.0000
18:36818972:TT:T	acceptor_gain	1.0000
18:36828677:CCTCA:C	donor_loss	1.0000
18:36828678:CTCA:C	donor_loss	1.0000
18:36828679:TCAC:T	donor_loss	1.0000
18:36828680:CACC:C	donor_loss	1.0000
18:36828681:ACC:A	donor_loss	1.0000
18:36779422:G:A	acceptor_gain	0.9900
18:36798443:CCTTA:C	donor_loss	0.9900
18:36798444:CTTAC:C	donor_loss	0.9900
18:36798445:TTAC:T	donor_loss	0.9900
18:36798446:T:TG	donor_loss	0.9900
18:36798448:CCTTG:C	donor_loss	0.9900
18:36798608:TG:T	acceptor_gain	0.9900
18:36798609:GC:G	acceptor_loss	0.9900
18:36798610:C:CC	acceptor_gain	0.9900
18:36798610:C:T	acceptor_loss	0.9900
18:36798615:G:GC	acceptor_gain	0.9900
18:36798623:C:CT	acceptor_gain	0.9900
18:36798624:A:T	acceptor_gain	0.9900
18:36800308:CTGG:C	acceptor_gain	0.9900
18:36800321:C:T	acceptor_gain	0.9900
18:36807930:TTCTT:T	acceptor_gain	0.9900
18:36807933:TT:T	acceptor_gain	0.9900
18:36818887:CACT:C	donor_loss	0.9900
18:36818889:CTTA:C	donor_loss	0.9900

AlphaMissense

1977 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:36798491:C:A	W205C	1.000
18:36798491:C:G	W205C	1.000
18:36798493:A:G	W205R	1.000
18:36798493:A:T	W205R	1.000
18:36807865:A:G	W79R	1.000
18:36807865:A:T	W79R	1.000
18:36818902:A:G	W53R	1.000
18:36818902:A:T	W53R	1.000
18:36797047:A:G	W221R	0.999
18:36797047:A:T	W221R	0.999
18:36798501:A:G	L202P	0.999
18:36798504:C:T	G201D	0.999
18:36798505:C:G	G201R	0.999
18:36798522:A:G	L195P	0.999
18:36798525:C:G	R194P	0.999
18:36798562:A:G	W182R	0.999
18:36798562:A:T	W182R	0.999
18:36798576:T:A	D177V	0.999
18:36798576:T:G	D177A	0.999
18:36798579:A:G	L176P	0.999
18:36798582:A:G	F175S	0.999
18:36798586:A:G	W174R	0.999
18:36798586:A:T	W174R	0.999
18:36800221:A:G	L158P	0.999
18:36800225:A:G	C157R	0.999
18:36800233:C:T	G154E	0.999
18:36800234:C:A	G154W	0.999
18:36800254:A:G	L147P	0.999
18:36805484:C:T	G91E	0.999
18:36807863:C:A	W79C	0.999

dbSNP variants (sampled 300 via entrez): RS1000096275 (18:36827143 A>C), RS1000098913 (18:36794298 T>C), RS1000128607 (18:36829946 T>A), RS1000148995 (18:36783934 T>C), RS1000149540 (18:36786962 G>C), RS1000377478 (18:36780831 G>A), RS1000403770 (18:36790467 C>T), RS1000482153 (18:36785497 T>C), RS1000511103 (18:36814978 TG>T), RS1000562672 (18:36830174 A>G), RS1000773356 (18:36821365 A>G), RS1000826325 (18:36817025 C>A), RS1000839456 (18:36819893 C>G), RS1000858107 (18:36811367 T>C,G), RS1000864785 (18:36811635 T>C)

Disease associations

OMIM: gene MIM:620710 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_99	Obesity-related traits	5.000000e-06
GCST002312_2	Periodontal disease-related phenotype (Socransky)	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
Cyclosporine	decreases expression	3
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
Temozolomide	decreases expression	1
Carbamazepine	affects expression	1
Estradiol	affects expression	1
Hydrogen Peroxide	affects expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation, increases expression	1
Lactic Acid	increases expression	1
tert-Butylhydroperoxide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2JF	Abcam HeLa TPGS2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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