GTPBP8

Summary

GTPBP8 (GTP binding protein 8, HGNC:25007) is a protein-coding gene on chromosome 3q13.2, encoding GTP-binding protein 8 (Q8N3Z3). It is a selective cancer dependency (DepMap: 11.3% of cell lines).

Predicted to enable GTP binding activity; GTPase activity; and metal ion binding activity. Located in mitochondrion.

Source: NCBI Gene 29083 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 57 total
• Cancer dependency (DepMap): dependent in 11.3% of screened cell lines
• MANE Select transcript: NM_014170

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25007
Approved symbol	GTPBP8
Name	GTP binding protein 8
Location	3q13.2
Locus type	gene with protein product
Status	Approved
Aliases	HSPC135
Ensembl gene	ENSG00000163607
Ensembl biotype	protein_coding
Entrez	29083

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 nonsense_mediated_decay

ENST00000295864, ENST00000383677, ENST00000383678, ENST00000467752, ENST00000473129, ENST00000485330, ENST00000488781, ENST00000939284

RefSeq mRNA: 2 — MANE Select: NM_014170 NM_014170, NM_138485

CCDS: CCDS33820, CCDS33821

Canonical transcript exons

ENST00000383678 — 6 exons

Exon	Start	End
ENSE00001838422	112990984	112991335
ENSE00001879336	113000850	113001969
ENSE00003514356	112999446	112999564
ENSE00003518141	112995135	112995265
ENSE00003524400	112993026	112993124
ENSE00003532487	112996892	112996991

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 96.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.3552 / max 57.6701, expressed in 1785 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37949	9.0177	1775
37948	2.1329	1249
37947	0.2045	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.01	gold quality
oocyte	CL:0000023	94.85	gold quality
endothelial cell	CL:0000115	94.41	gold quality
sperm	CL:0000019	93.78	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.23	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.18	gold quality
biceps brachii	UBERON:0001507	93.13	gold quality
vastus lateralis	UBERON:0001379	92.28	gold quality
male germ cell	CL:0000015	92.21	gold quality
quadriceps femoris	UBERON:0001377	91.38	gold quality
superior surface of tongue	UBERON:0007371	90.83	gold quality
body of tongue	UBERON:0011876	90.78	gold quality
epithelium of nasopharynx	UBERON:0001951	90.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.64	gold quality
triceps brachii	UBERON:0001509	90.40	gold quality
skeletal muscle tissue	UBERON:0001134	90.34	gold quality
heart right ventricle	UBERON:0002080	90.12	gold quality
pylorus	UBERON:0001166	90.02	gold quality
tongue	UBERON:0001723	89.89	gold quality
parietal pleura	UBERON:0002400	89.82	gold quality
visceral pleura	UBERON:0002401	89.81	gold quality
palpebral conjunctiva	UBERON:0001812	89.50	gold quality
hair follicle	UBERON:0002073	89.48	gold quality
pleura	UBERON:0000977	89.35	gold quality
pharyngeal mucosa	UBERON:0000355	89.29	gold quality
cervix squamous epithelium	UBERON:0006922	89.19	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.05	gold quality
diaphragm	UBERON:0001103	89.05	gold quality
gluteal muscle	UBERON:0002000	89.00	gold quality
nipple	UBERON:0002030	88.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting GTPBP8, 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-3925-3P	100.00	69.95	1237
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-4678	97.59	68.31	902
HSA-MIR-6824-5P	97.41	68.43	583
HSA-MIR-411-5P	97.11	66.82	601
HSA-MIR-4764-3P	96.81	67.94	580
HSA-MIR-5591-3P	96.23	67.03	489

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• GTPBP8 modulates mitochondrial fission through a Drp1-dependent process. (PMID:38587461)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtpbp8	ENSDARG00000075033
mus_musculus	Gtpbp8	ENSMUSG00000022668
rattus_norvegicus	Gtpbp8	ENSRNOG00000002044

Protein

Protein identifiers

GTP-binding protein 8 — Q8N3Z3 (reviewed: Q8N3Z3)

All UniProt accessions (4): C9J0K3, C9J8V5, Q8N3Z3, F8WBY6

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. EngB GTPase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N3Z3-1	1	yes
Q8N3Z3-2	2
Q8N3Z3-3	3

RefSeq proteins (2): NP_054889, NP_612494 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006073	GTP-bd	Domain
IPR019987	GTP-bd_ribosome_bio_YsxC	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030393	G_ENGB_dom	Domain
IPR052279	EngB_GTPase	Family

Pfam: PF01926

UniProt features (14 total): binding site 7, splice variant 3, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3Z3-F1	85.06	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (7): 117–124; 124; 146–150; 148; 164–167; 226–229; 261–263

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): BLALOCK_ALZHEIMERS_DISEASE_UP, TGTGTGA_MIR377, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, STEIN_ESRRA_TARGETS_UP, PUIFFE_INVASION_INHIBITED_BY_ASCITES_DN, MARTENS_TRETINOIN_RESPONSE_DN, YTCCCRNNAGGY_UNKNOWN, ONKEN_UVEAL_MELANOMA_DN, CSR_EARLY_UP.V1_DN, TBK1.DF_DN, ARID5B_TARGET_GENES, DLX4_TARGET_GENES, F10_TARGET_GENES, FEV_TARGET_GENES, HOXB4_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (5): GTP binding (GO:0005525), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), GTPase activity (GO:0003924), protein binding (GO:0005515)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ribonucleoside triphosphate phosphatase activity	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1165 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTPBP8	MTG2	Q9H4K7	712
GTPBP8	GTPBP10	A4D1E9	709
GTPBP8	MTG1	Q9BT17	700
GTPBP8	GTPBP6	O43824	667
GTPBP8	DDX28	Q9NUL7	666
GTPBP8	RMP64	Q6NW34	573
GTPBP8	ERAL1	O75616	560
GTPBP8	GRAMD1C	Q8IYS0	559
GTPBP8	NOA1	Q8NC60	535
GTPBP8	PET117	Q6UWS5	527
GTPBP8	MALSU1	Q96EH3	512
GTPBP8	SPICE1	Q8N0Z3	505
GTPBP8	GTPBP3	Q969Y2	499
GTPBP8	BOLA1	Q9Y3E2	489
GTPBP8	GPHRA	B7ZAQ6	488

IntAct

26 interactions, top by confidence:

A	B	Type	Score
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
GTPBP8	CDC23	psi-mi:“MI:0915”(physical association)	0.560
GTPBP8	HSPD1	psi-mi:“MI:0914”(association)	0.530
YBEY	NME4	psi-mi:“MI:0914”(association)	0.530
MAPT	LANCL1	psi-mi:“MI:0914”(association)	0.350
YBEY	NUDT19	psi-mi:“MI:0914”(association)	0.350
NIT1	NUDT19	psi-mi:“MI:0914”(association)	0.350
MRPL12		psi-mi:“MI:0914”(association)	0.350
MRPL21		psi-mi:“MI:0914”(association)	0.350
IMPDH1	LCMT2	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
MALSU1	VWA8	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
MRPS25	ZNF865	psi-mi:“MI:0914”(association)	0.350
COQ5	HSPD1	psi-mi:“MI:0914”(association)	0.350
MRPL21	FDXR	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
TEAD3	PDHA1	psi-mi:“MI:0914”(association)	0.350
GTPBP8	CDC23	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): GTPBP8 (Affinity Capture-MS), GTPBP8 (Synthetic Growth Defect), GTPBP8 (Affinity Capture-MS), AMIGO3 (Affinity Capture-MS), GTPBP8 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), LAMP2 (Affinity Capture-MS), GTPBP8 (Affinity Capture-MS), GTPBP8 (Affinity Capture-MS), GTPBP8 (Affinity Capture-MS), GTPBP8 (Two-hybrid), GTPBP8 (Affinity Capture-RNA), GTPBP8 (Affinity Capture-MS), GTPBP8 (Affinity Capture-MS), GTPBP8 (Affinity Capture-MS)

ESM2 similar proteins: A6QPQ5, A9X1A9, O95707, P0C2C1, P82664, P82670, P82675, P82915, P82919, P82933, Q08BI9, Q0P5E7, Q0VFH6, Q2KIB9, Q2KID9, Q2KIJ6, Q2TBK2, Q2TBR2, Q3MHY7, Q3SYS0, Q3T040, Q58DQ5, Q58DV5, Q5C9Z4, Q5R7B0, Q5REJ1, Q5REY4, Q5RFM3, Q641X9, Q7Z2W9, Q7Z7H8, Q8N3Z3, Q8TCC3, Q924T2, Q99N85, Q99N87, Q99N94, Q9BSH4, Q9BYD2, Q9BYD6

Diamond homologs: A0M537, A0Q2K7, A0Q6R7, A1KS92, A2RF16, A4IYA4, A5FIZ1, A5G964, A5IMB8, A5IXT1, A5N2K5, A5VJ95, A6H1A5, A6L4J3, A6LBY4, A6USY3, A7NBT0, A8YUS5, A9M1V2, B0K530, B0KBA1, B0R871, B0S8I0, B1AIQ5, B1LBK5, B1MXT9, B2A1E8, B2G6R5, B2SG30, B3PN57, B4RQ29, B5EEM1, B5ZB76, B7IDZ1, B8I8N7, B9K8C0, B9LNM9, B9LZU0, C6E8C5, O05132

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2029 predictions. Top by Δscore:

Variant	Effect	Δscore
3:112991333:GAG:G	donor_gain	1.0000
3:112993125:G:GG	donor_gain	1.0000
3:112995262:GGAA:G	donor_gain	1.0000
3:112995263:G:T	donor_gain	1.0000
3:112995263:GAA:G	donor_gain	1.0000
3:112995263:GAAG:G	donor_gain	1.0000
3:112995266:G:GG	donor_gain	1.0000
3:112995272:A:T	donor_gain	1.0000
3:112996881:C:G	acceptor_gain	1.0000
3:112996882:A:AG	acceptor_gain	1.0000
3:112996882:AT:A	acceptor_gain	1.0000
3:112996883:T:G	acceptor_gain	1.0000
3:112996887:TATA:T	acceptor_loss	1.0000
3:112996889:TA:T	acceptor_loss	1.0000
3:112996890:A:AC	acceptor_loss	1.0000
3:112996890:A:AG	acceptor_gain	1.0000
3:112996891:G:GG	acceptor_gain	1.0000
3:112996891:G:GT	acceptor_loss	1.0000
3:112996891:GCTT:G	acceptor_gain	1.0000
3:112996988:TGTGG:T	donor_loss	1.0000
3:112996989:GTG:G	donor_gain	1.0000
3:112996992:G:A	donor_loss	1.0000
3:112996992:G:GG	donor_gain	1.0000
3:112996993:TAAG:T	donor_loss	1.0000
3:112999443:T:G	acceptor_gain	1.0000
3:112999443:TAGAT:T	acceptor_loss	1.0000
3:112999444:A:AG	acceptor_gain	1.0000
3:112999444:AG:A	acceptor_loss	1.0000
3:112999444:AGATT:A	acceptor_gain	1.0000
3:112999445:G:GT	acceptor_gain	1.0000

AlphaMissense

1853 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:112993057:A:T	K123I	0.999
3:112999459:A:T	K227I	0.999
3:112993054:G:A	G122E	0.998
3:112995196:C:A	P166Q	0.998
3:112993029:T:C	C114R	0.997
3:112993031:T:G	C114W	0.997
3:112993039:G:A	G117D	0.997
3:112993044:A:C	S119R	0.997
3:112993046:C:A	S119R	0.997
3:112993046:C:G	S119R	0.997
3:112993053:G:A	G122R	0.997
3:112993053:G:C	G122R	0.997
3:112993056:A:C	K123Q	0.997
3:112996944:G:C	D207H	0.997
3:112993038:G:C	G117R	0.996
3:112993054:G:T	G122V	0.996
3:112993058:A:C	K123N	0.996
3:112993058:A:T	K123N	0.996
3:112993066:T:C	L126P	0.996
3:112995189:G:C	D164H	0.996
3:112995190:A:C	D164A	0.996
3:112995190:A:G	D164G	0.996
3:112995199:G:A	G167D	0.996
3:112993039:G:T	G117V	0.995
3:112995136:G:A	G146E	0.995
3:112995225:T:C	F176L	0.995
3:112995227:T:A	F176L	0.995
3:112995227:T:G	F176L	0.995
3:112995250:T:C	L184P	0.995
3:112996954:C:A	A210D	0.995

dbSNP variants (sampled 300 via entrez): RS1000204918 (3:112993537 C>T), RS1000432779 (3:112993331 A>G), RS1000462145 (3:113000186 C>T), RS1000832804 (3:113000439 G>A), RS1000865728 (3:112992981 G>A), RS1001281376 (3:112991556 A>G), RS1001417700 (3:112998952 T>C), RS1001499538 (3:112992306 A>T), RS1001633562 (3:112992628 C>T), RS1001683032 (3:112999013 T>C), RS1001891779 (3:112998620 G>A), RS1002218863 (3:112999353 T>C), RS1002231584 (3:112990921 T>A,C), RS1002282549 (3:112990609 C>G), RS1002504184 (3:112991058 T>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
Particulate Matter	decreases reaction, increases expression, decreases expression, increases abundance	2
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	increases expression	1
K 7174	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
picoxystrobin	increases expression	1
Temozolomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Dexamethasone	increases expression	1
Diethylstilbestrol	decreases expression	1
Colforsin	decreases reaction, increases expression	1
Ketoconazole	decreases expression	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Selenium	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Vitamin E	affects cotreatment, decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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