GTPBP4

Summary

GTPBP4 (GTP binding protein 4, HGNC:21535) is a protein-coding gene on chromosome 10p15.3, encoding GTP-binding protein 4 (Q9BZE4). Involved in the biogenesis of the 60S ribosomal subunit. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

GTP-binding proteins are GTPases and function as molecular switches that can flip between two states: active, when GTP is bound, and inactive, when GDP is bound. ‘Active’ in this context usually means that the molecule acts as a signal to trigger other events in the cell. When an extracellular ligand binds to a G-protein-linked receptor, the receptor changes its conformation and switches on the trimeric G proteins that associate with it by causing them to eject their GDP and replace it with GTP. The switch is turned off when the G protein hydrolyzes its own bound GTP, converting it back to GDP. But before that occurs, the active protein has an opportunity to diffuse away from the receptor and deliver its message for a prolonged period to its downstream target.

Source: NCBI Gene 23560 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 143 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_012341

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21535
Approved symbol	GTPBP4
Name	GTP binding protein 4
Location	10p15.3
Locus type	gene with protein product
Status	Approved
Aliases	CRFG, NGB, FLJ10690, FLJ10686, NOG1
Ensembl gene	ENSG00000107937
Ensembl biotype	protein_coding
OMIM	619169
Entrez	23560

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000360059, ENST00000360803, ENST00000483839, ENST00000491261, ENST00000491635, ENST00000892145, ENST00000892146, ENST00000892147, ENST00000892148, ENST00000892149, ENST00000892150, ENST00000925420, ENST00000925421, ENST00000925422, ENST00000925423, ENST00000925424, ENST00000925425

RefSeq mRNA: 1 — MANE Select: NM_012341 NM_012341

CCDS: CCDS31132

Canonical transcript exons

ENST00000360803 — 17 exons

Exon	Start	End
ENSE00000688071	1010420	1010520
ENSE00001094477	995929	996032
ENSE00001363971	988434	988527
ENSE00001430355	1017075	1019932
ENSE00001488520	1012465	1012662
ENSE00003467055	1005818	1005907
ENSE00003474273	1015753	1015896
ENSE00003490454	1014247	1014312
ENSE00003505248	1000948	1001013
ENSE00003513912	1009529	1009580
ENSE00003545578	999003	999095
ENSE00003572712	1008958	1009035
ENSE00003576216	996106	996242
ENSE00003613229	1000677	1000868
ENSE00003628701	1007018	1007128
ENSE00003673867	992489	992659
ENSE00003791514	997208	997308

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 96.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.5876 / max 398.8763, expressed in 1814 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103426	46.9985	1814
103429	0.5505	265
103427	0.0272	7
103428	0.0114	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.61	gold quality
adrenal tissue	UBERON:0018303	96.57	gold quality
male germ cell	CL:0000015	95.66	gold quality
epithelium of nasopharynx	UBERON:0001951	95.42	gold quality
calcaneal tendon	UBERON:0003701	94.90	gold quality
mucosa of urinary bladder	UBERON:0001259	94.67	gold quality
amniotic fluid	UBERON:0000173	94.25	gold quality
cartilage tissue	UBERON:0002418	94.07	gold quality
stromal cell of endometrium	CL:0002255	94.01	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.92	gold quality
right adrenal gland cortex	UBERON:0035827	93.63	gold quality
gastrocnemius	UBERON:0001388	93.49	gold quality
adrenal gland	UBERON:0002369	93.45	gold quality
tendon	UBERON:0000043	93.35	gold quality
adrenal cortex	UBERON:0001235	93.28	gold quality
right adrenal gland	UBERON:0001233	93.26	gold quality
left adrenal gland	UBERON:0001234	93.15	gold quality
palpebral conjunctiva	UBERON:0001812	93.15	gold quality
left adrenal gland cortex	UBERON:0035825	92.96	gold quality
pericardium	UBERON:0002407	92.94	gold quality
muscle of leg	UBERON:0001383	92.86	gold quality
hair follicle	UBERON:0002073	92.85	gold quality
penis	UBERON:0000989	92.83	gold quality
sural nerve	UBERON:0015488	92.79	gold quality
germinal epithelium of ovary	UBERON:0001304	92.67	gold quality
gingival epithelium	UBERON:0001949	92.62	gold quality
medial globus pallidus	UBERON:0002477	92.60	gold quality
esophagus squamous epithelium	UBERON:0006920	92.57	gold quality
mammary duct	UBERON:0001765	92.54	gold quality
squamous epithelium	UBERON:0006914	92.46	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	45.24
E-MTAB-7303	no	1765.42
E-CURD-95	no	216.39
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting GTPBP4, 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-3646	100.00	73.56	5283
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-1261	98.62	68.10	896
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-934	98.49	70.44	581
HSA-MIR-556-5P	97.75	66.17	473
HSA-MIR-610	96.84	67.98	905

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• NGB is a tumor suppressor that regulates and requires merlin to suppress cell proliferation (PMID:17210637)
• GTPBP4 promotes colorectal cancer metastasis by disrupting actin cytoskeleton, which is mediated by the reduced RhoA activity.Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis. (PMID:27720713)
• Determining the Clinical Value and Critical Pathway of GTPBP4 in Lung Adenocarcinoma Using a Bioinformatics Strategy: A Study Based on Datasets from The Cancer Genome Atlas. (PMID:33134380)
• An Integrating Immune-Related Signature to Improve Prognosis of Hepatocellular Carcinoma. (PMID:33204302)
• LncRNA FGD5-AS1 functions as an oncogene to upregulate GTPBP4 expression by sponging miR-873-5p in hepatocellular carcinoma. (PMID:34783233)
• GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism. (PMID:36116159)
• NOG1 downregulates type I interferon production by targeting phosphorylated interferon regulatory factor 3. (PMID:37410776)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtpbp4	ENSDARG00000018961
mus_musculus	Gtpbp4	ENSMUSG00000021149
rattus_norvegicus	Gtpbp4	ENSRNOG00000016217
rattus_norvegicus		ENSRNOG00000085666
drosophila_melanogaster	Non1	FBGN0028473
caenorhabditis_elegans		WBGENE00020297

Paralogs (4): MTG2 (ENSG00000101181), GTPBP10 (ENSG00000105793), DRG2 (ENSG00000108591), DRG1 (ENSG00000185721)

Protein

Protein identifiers

GTP-binding protein 4 — Q9BZE4 (reviewed: Q9BZE4)

Alternative names: Chronic renal failure gene protein, GTP-binding protein NGB, Nucleolar GTP-binding protein 1

All UniProt accessions (3): Q9BZE4, D2CFK9, Q5T3R7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the biogenesis of the 60S ribosomal subunit. Acts as a TP53 repressor, preventing TP53 stabilization and cell cycle arrest.

Subunit / interactions. Associates with pre-60S ribosomal particles. Interacts with MINAS-60 (product of an alternative open reading frame of RBM10).

Subcellular location. Nucleus. Nucleolus.

Similarity. Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. NOG subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BZE4-1	1	yes
Q9BZE4-2	2
Q9BZE4-3	3

RefSeq proteins (1): NP_036473* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005225	Small_GTP-bd	Domain
IPR006073	GTP-bd	Domain
IPR010674	NOG1_Rossman_fold_dom	Domain
IPR012973	NOG_C	Domain
IPR024926	NOG1	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031167	G_OBG	Domain
IPR041623	NOG1_N	Domain

Pfam: PF06858, PF08155, PF17835

UniProt features (29 total): modified residue 8, compositionally biased region 6, binding site 3, cross-link 3, splice variant 2, region of interest 2, initiator methionine 1, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

39 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8FKV	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
8FKW	ELECTRON MICROSCOPY	2.5
8FL3	ELECTRON MICROSCOPY	2.53
8FL7	ELECTRON MICROSCOPY	2.55
8FLB	ELECTRON MICROSCOPY	2.55
8FLD	ELECTRON MICROSCOPY	2.58
8FKX	ELECTRON MICROSCOPY	2.59
8FL6	ELECTRON MICROSCOPY	2.62
8FLA	ELECTRON MICROSCOPY	2.63
8FLF	ELECTRON MICROSCOPY	2.65
8FKY	ELECTRON MICROSCOPY	2.67
8FL2	ELECTRON MICROSCOPY	2.67
8FL9	ELECTRON MICROSCOPY	2.75
8FKQ	ELECTRON MICROSCOPY	2.76
8FLC	ELECTRON MICROSCOPY	2.76
8IDT	ELECTRON MICROSCOPY	2.8
8FKT	ELECTRON MICROSCOPY	2.81
8FKU	ELECTRON MICROSCOPY	2.82
8RL2	ELECTRON MICROSCOPY	2.84
8FKP	ELECTRON MICROSCOPY	2.85
8FKS	ELECTRON MICROSCOPY	2.88
8FKR	ELECTRON MICROSCOPY	2.89
8FL4	ELECTRON MICROSCOPY	2.89
8FL0	ELECTRON MICROSCOPY	2.91
8IDY	ELECTRON MICROSCOPY	3
8INF	ELECTRON MICROSCOPY	3
8FKZ	ELECTRON MICROSCOPY	3.04
9QIW	ELECTRON MICROSCOPY	3.04
6LU8	ELECTRON MICROSCOPY	3.13

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZE4-F1	83.45	0.38

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 (3): 175–182; 221–225; 289–292

Post-translational modifications (11): 2, 103, 122, 468, 470, 472, 522, 558, 103, 332, 534

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 271 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, chr14q24, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_LEVELS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP

GO Biological Process (11): maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000463), osteoblast differentiation (GO:0001649), negative regulation of DNA replication (GO:0008156), negative regulation of cell population proliferation (GO:0008285), negative regulation of G2/M transition of mitotic cell cycle (GO:0010972), negative regulation of cell-cell adhesion (GO:0022408), negative regulation of cell migration (GO:0030336), negative regulation of protein ubiquitination (GO:0031397), ribosomal large subunit biogenesis (GO:0042273), protein stabilization (GO:0050821), ribosome biogenesis (GO:0042254)

GO Molecular Function (6): RNA binding (GO:0003723), GTPase activity (GO:0003924), GTP binding (GO:0005525), preribosome binding (GO:1990275), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
ribonucleoprotein complex biogenesis	2
nuclear lumen	2
cytoplasm	2
maturation of LSU-rRNA	1
ossification	1
cell differentiation	1
DNA replication	1
regulation of DNA replication	1
negative regulation of DNA metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G2/M phase transition	1
negative regulation of cell adhesion	1
regulation of cell-cell adhesion	1
cell-cell adhesion	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
ribosome biogenesis	1
regulation of protein stability	1
nucleic acid binding	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoprotein complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
nucleus	1

Protein interactions and networks

STRING

3998 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTPBP4	RSL24D1	Q9UHA3	941
GTPBP4	GNL2	Q13823	910
GTPBP4	NSA2	O95478	892
GTPBP4	RHO	P08100	854
GTPBP4	GTPBP6	O43824	832
GTPBP4	RPF2	Q9H7B2	824
GTPBP4	MRTO4	Q9UKD2	802
GTPBP4	MTG1	Q9BT17	793
GTPBP4	GSPT1	P15170	786
GTPBP4	GTPBP3	Q969Y2	785
GTPBP4	NCF2	P19878	784
GTPBP4	NCF4	Q15080	763
GTPBP4	NCF1	P14598	759
GTPBP4	NMD3	Q96D46	727
GTPBP4	GSPT2	Q8IYD1	725
GTPBP4	NOP2	P46087	725

IntAct

379 interactions, top by confidence:

A	B	Type	Score
PIK3CB	PIK3R2	psi-mi:“MI:0914”(association)	0.860
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PTK2	TGFB1I1	psi-mi:“MI:0914”(association)	0.680
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
NF2	GTPBP4	psi-mi:“MI:0915”(physical association)	0.610
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
COPB1	GTPBP4	psi-mi:“MI:0915”(physical association)	0.560
HTT	GTPBP4	psi-mi:“MI:0915”(physical association)	0.560
EED	EPOP	psi-mi:“MI:0914”(association)	0.530
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
NSA2	TYW5	psi-mi:“MI:0914”(association)	0.530
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530

BioGRID (554): GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS), GTPBP4 (Affinity Capture-MS)

ESM2 similar proteins: A2VEI2, A8WQT4, B3MIF1, D6WIX5, O70200, P41044, P55008, P55009, P81076, Q02892, Q1LY46, Q21153, Q295E6, Q3UQ44, Q5E9G1, Q5E9R3, Q5RBP4, Q5TM25, Q5ZK33, Q641Z6, Q6AXZ3, Q6CM00, Q6DJ05, Q6FRV0, Q6GQ76, Q74ZK6, Q803R5, Q803V3, Q8CD10, Q8IQ70, Q8IYU8, Q8R491, Q94CF0, Q95PZ2, Q969Q6, Q99P77, Q9BDK2, Q9BZE4, Q9EQP2, Q9FEE2

Diamond homologs: A3QB95, A8FRU4, B0U3R3, B2I6V6, B4RZH3, B8CSY3, C0QX49, G0S8F1, O44411, O94659, P17103, P34280, P39729, P53295, Q02892, Q15PF0, Q2S3C0, Q493U5, Q54HP3, Q54N72, Q54WT4, Q58722, Q58803, Q58D56, Q6CM00, Q6FRV0, Q73LW4, Q74ZK6, Q87BL2, Q8SVJ8, Q99ME9, Q99P77, Q9BZE4, Q9C6I8, Q9CAI1, Q9LQK0, Q9PAS3, Q9QXB9, Q9SVA6, Q9U6A9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 224 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
SRP-dependent cotranslational protein targeting to membrane	19	12.9×	2e-13
Peptide chain elongation	15	12.9×	6e-11
Viral mRNA Translation	15	12.9×	6e-11
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	15	12.8×	6e-11
Selenocysteine synthesis	15	12.3×	8e-11
Eukaryotic Translation Termination	15	12.3×	8e-11
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	15	12.0×	9e-11
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	15	12.0×	9e-11

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal large subunit biogenesis	8	17.7×	3e-06
motor neuron axon guidance	5	17.6×	1e-03
cytoplasmic translation	17	15.7×	7e-13
negative regulation of viral genome replication	6	11.2×	2e-03
rRNA processing	14	9.9×	6e-08
regulation of signal transduction by p53 class mediator	5	9.6×	1e-02
translation	18	9.2×	7e-10
ribosomal small subunit biogenesis	8	9.1×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	104
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2559 predictions. Top by Δscore:

Variant	Effect	Δscore
10:1000673:TTAG:T	acceptor_loss	1.0000
10:1000674:TA:T	acceptor_loss	1.0000
10:1000675:A:AT	acceptor_loss	1.0000
10:1000676:G:GC	acceptor_loss	1.0000
10:1000943:CCTA:C	acceptor_loss	1.0000
10:1000945:TA:T	acceptor_loss	1.0000
10:1000946:A:AC	acceptor_loss	1.0000
10:1000946:A:AG	acceptor_gain	1.0000
10:1000947:G:GG	acceptor_gain	1.0000
10:1000947:G:GT	acceptor_loss	1.0000
10:1001009:ATCAG:A	donor_loss	1.0000
10:1001010:TCAG:T	donor_loss	1.0000
10:1001011:CAGG:C	donor_loss	1.0000
10:1001012:AGGT:A	donor_loss	1.0000
10:1001013:GGTAA:G	donor_loss	1.0000
10:1001014:G:GA	donor_loss	1.0000
10:1001015:T:G	donor_loss	1.0000
10:1005810:A:AG	acceptor_gain	1.0000
10:1005811:T:G	acceptor_gain	1.0000
10:1005817:GAAA:G	acceptor_gain	1.0000
10:1007124:ATAAG:A	donor_loss	1.0000
10:1007125:TAAGG:T	donor_loss	1.0000
10:1007129:G:A	donor_loss	1.0000
10:1007130:T:A	donor_loss	1.0000
10:1009579:GA:G	donor_gain	1.0000
10:1009581:G:GG	donor_gain	1.0000
10:1012444:A:AG	acceptor_gain	1.0000
10:1012447:A:AG	acceptor_gain	1.0000
10:1012449:A:AG	acceptor_gain	1.0000
10:1012450:A:G	acceptor_gain	1.0000

AlphaMissense

4232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:1000683:G:C	D221H	1.000
10:1000690:C:A	P223H	1.000
10:1000692:G:A	G224R	1.000
10:1000692:G:C	G224R	1.000
10:1000692:G:T	G224W	1.000
10:1000693:G:A	G224E	1.000
10:1000733:G:C	E237D	1.000
10:1000733:G:T	E237D	1.000
10:1000740:G:C	A240P	1.000
10:1000750:C:A	A243D	1.000
10:1000970:A:T	K290I	1.000
10:1000971:A:C	K290N	1.000
10:1000971:A:T	K290N	1.000
10:992523:G:C	R28P	1.000
10:992576:T:C	F46L	1.000
10:992578:T:A	F46L	1.000
10:992578:T:G	F46L	1.000
10:992590:A:C	K50N	1.000
10:992590:A:T	K50N	1.000
10:992592:T:A	V51D	1.000
10:995996:T:C	L96P	1.000
10:996141:G:A	G120D	1.000
10:996158:T:C	C126R	1.000
10:996159:G:A	C126Y	1.000
10:996160:C:G	C126W	1.000
10:996168:T:C	L129P	1.000
10:996172:G:C	K130N	1.000
10:996172:G:T	K130N	1.000
10:996179:G:C	A133P	1.000
10:996180:C:A	A133D	1.000

dbSNP variants (sampled 300 via entrez): RS1000009560 (10:1002184 G>A,T), RS1000057898 (10:993665 G>A,T), RS1000206510 (10:1009370 A>G), RS1000240402 (10:987970 C>A,T), RS1000290729 (10:999386 G>A,C), RS1000380923 (10:988327 T>C,G), RS1000404928 (10:1010189 A>C,T), RS1000492117 (10:1014842 C>T), RS1000510781 (10:993037 C>T), RS1000646896 (10:998702 A>G), RS1000688320 (10:999053 T>G), RS1000701932 (10:1020231 T>C), RS1000756528 (10:1010026 G>A,T), RS1001021843 (10:998873 C>T), RS1001026424 (10:987659 G>A)

Disease associations

OMIM: gene MIM:619169 | 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
GCST008163_605	Height	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105780 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,020 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL3545360	ASP-3026	1	665

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

ChEMBL bioactivities

6 potent at pChembl≥5 of 6 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.05	Kd	9	nM	ASP-3026
6.23	Kd	592.6	nM	CHEMBL5653589
6.23	ED50	592.6	nM	CHEMBL5653589
5.53	Kd	2950	nM	CHEMBL3752910
5.53	ED50	2950	nM	CHEMBL3752910
5.09	Kd	8198	nM	SOTRASTAURIN

PubChem BioAssay actives

4 with measured affinity, of 231 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine	1425016: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0090	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148478: Binding affinity to human GTPBP4 incubated for 45 mins by Kinobead based pull down assay	kd	0.5926	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148478: Binding affinity to human GTPBP4 incubated for 45 mins by Kinobead based pull down assay	kd	2.9496	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1425016: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	8.1980	uM

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	decreases expression, increases expression, affects cotreatment	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
TL8-506	increases expression, affects cotreatment	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
tetrahydropalmatine	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
nivalenol	increases expression	1
isobutyl alcohol	decreases expression, increases abundance, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression, increases reaction	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Glyphosate	affects methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Benztropine	increases expression	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991729	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

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