TRUB2

Summary

TRUB2 (TruB pseudouridine synthase family member 2, HGNC:17170) is a protein-coding gene on chromosome 9q34.11, encoding Pseudouridylate synthase TRUB2, mitochondrial (O95900). Minor enzyme contributing to the isomerization of uridine to pseudouridine (pseudouridylation) of specific mitochondrial mRNAs (mt-mRNAs) such as COXI and COXIII mt-mRNAs. It is a selective cancer dependency (DepMap: 25.2% of cell lines).

Pseudouridine is an abundant component of rRNAs and tRNAs and is enzymatically generated by isomerization of uridine by pseudouridine synthase (Zucchini et al., 2003 [PubMed 12736709]).

Source: NCBI Gene 26995 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 75 total
• Cancer dependency (DepMap): dependent in 25.2% of screened cell lines
• MANE Select transcript: NM_015679

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17170
Approved symbol	TRUB2
Name	TruB pseudouridine synthase family member 2
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	CLONE24922
Ensembl gene	ENSG00000167112
Ensembl biotype	protein_coding
OMIM	610727
Entrez	26995

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000372890, ENST00000460320, ENST00000461180, ENST00000853279, ENST00000853280, ENST00000853281, ENST00000853282, ENST00000925515, ENST00000925516

RefSeq mRNA: 4 — MANE Select: NM_015679 NM_001329861, NM_001329862, NM_001329863, NM_015679

CCDS: CCDS6897

Canonical transcript exons

ENST00000372890 — 8 exons

Exon	Start	End
ENSE00001109877	128305159	128309875
ENSE00001875069	128322300	128322447
ENSE00003465144	128315567	128315628
ENSE00003547598	128311529	128311601
ENSE00003639632	128317152	128317226
ENSE00003640982	128310887	128311023
ENSE00003642369	128313808	128313889
ENSE00003642950	128321599	128321730

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 94.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.7048 / max 189.8923, expressed in 1793 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102683	26.7048	1793

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	94.41	silver quality
pons	UBERON:0000988	92.84	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.65	gold quality
prefrontal cortex	UBERON:0000451	92.16	gold quality
inferior vagus X ganglion	UBERON:0005363	91.68	silver quality
substantia nigra pars compacta	UBERON:0001965	91.35	silver quality
substantia nigra pars reticulata	UBERON:0001966	90.93	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.77	silver quality
lateral globus pallidus	UBERON:0002476	90.73	silver quality
right adrenal gland	UBERON:0001233	90.47	gold quality
ventral tegmental area	UBERON:0002691	90.45	silver quality
subthalamic nucleus	UBERON:0001906	90.33	silver quality
apex of heart	UBERON:0002098	90.29	gold quality
superior vestibular nucleus	UBERON:0007227	89.93	silver quality
midbrain	UBERON:0001891	89.88	gold quality
substantia nigra	UBERON:0002038	89.87	gold quality
left adrenal gland	UBERON:0001234	89.73	gold quality
nipple	UBERON:0002030	89.70	silver quality
right adrenal gland cortex	UBERON:0035827	89.67	gold quality
renal medulla	UBERON:0000362	89.65	gold quality
mucosa of transverse colon	UBERON:0004991	89.64	gold quality
frontal cortex	UBERON:0001870	89.56	gold quality
medulla oblongata	UBERON:0001896	89.49	silver quality
pancreatic ductal cell	CL:0002079	89.28	silver quality
adrenal gland	UBERON:0002369	89.18	gold quality
hypothalamus	UBERON:0001898	89.16	gold quality
heart left ventricle	UBERON:0002084	89.15	gold quality
putamen	UBERON:0001874	89.10	gold quality
adrenal cortex	UBERON:0001235	89.06	gold quality
cardiac ventricle	UBERON:0002082	89.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.01
E-MTAB-7249	no	82.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting TRUB2, 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-4267	99.96	66.53	2368
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-550A-3P	98.37	69.61	632
HSA-MIR-599	98.32	66.99	1037
HSA-MIR-200C-5P	97.71	67.73	596
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-1277-3P	93.47	68.97	156

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Mammalian nuclear TRUB1, mitochondrial TRUB2, and cytoplasmic PUS10 produce conserved pseudouridine 55 in different sets of tRNA. (PMID:33023933)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	trub2	ENSDARG00000028379
mus_musculus	Trub2	ENSMUSG00000039826
rattus_norvegicus	Trub2	ENSRNOG00000043189
rattus_norvegicus		ENSRNOG00000074520
rattus_norvegicus		ENSRNOG00000088140
drosophila_melanogaster	CG7849	FBGN0033060
caenorhabditis_elegans		WBGENE00021544

Protein

Protein identifiers

Pseudouridylate synthase TRUB2, mitochondrial — O95900 (reviewed: O95900)

Alternative names: TruB pseudouridine synthase homolog 2, tRNA pseudouridine 55 synthase TRUB2

All UniProt accessions (1): O95900

UniProt curated annotations — full annotation on UniProt →

Function. Minor enzyme contributing to the isomerization of uridine to pseudouridine (pseudouridylation) of specific mitochondrial mRNAs (mt-mRNAs) such as COXI and COXIII mt-mRNAs. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation. Also catalyzes pseudouridylation of some tRNAs, including synthesis of pseudouridine(55) from uracil-55, in the psi GC loop of a subset of tRNAs.

Subunit / interactions. Forms a regulatory protein-RNA complex, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA.

Subcellular location. Mitochondrion matrix.

Similarity. Belongs to the pseudouridine synthase TruB family.

Isoforms (2)

UniProt ID	Names	Canonical?
O95900-1	1	yes
O95900-2	2

RefSeq proteins (4): NP_001316790, NP_001316791, NP_001316792, NP_056494* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002501	PsdUridine_synth_N	Domain
IPR020103	PsdUridine_synth_cat_dom_sf	Homologous_superfamily
IPR039048	Trub2	Family

Pfam: PF01509

Catalyzed reactions (Rhea), 2 shown:

• uridine(55) in tRNA = pseudouridine(55) in tRNA (RHEA:42532)
• a uridine in mRNA = a pseudouridine in mRNA (RHEA:56644)

UniProt features (9 total): sequence variant 3, transit peptide 1, chain 1, region of interest 1, compositionally biased region 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95900-F1	85.94	0.61

Functional residue map

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

Catalytic / active sites (1): 98 (nucleophile)

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6793080	rRNA modification in the mitochondrion
R-HSA-9937008	Mitochondrial mRNA modification

MSigDB gene sets: 132 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_MRNA_MODIFICATION, GOBP_PSEUDOURIDINE_SYNTHESIS, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_RNA_MODIFICATION, GOBP_MITOCHONDRIAL_RNA_PROCESSING, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, WANG_TARGETS_OF_MLL_CBP_FUSION_UP, USF_02

GO Biological Process (9): mRNA processing (GO:0006397), mRNA modification (GO:0016556), positive regulation of mitochondrial translation (GO:0070131), mitochondrial tRNA pseudouridine synthesis (GO:0070902), mRNA pseudouridine synthesis (GO:1990481), pseudouridine synthesis (GO:0001522), RNA processing (GO:0006396), tRNA processing (GO:0008033), RNA modification (GO:0009451)

GO Molecular Function (4): RNA binding (GO:0003723), pseudouridine synthase activity (GO:0009982), tRNA pseudouridine(55) synthase activity (GO:0160148), isomerase activity (GO:0016853)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), ribonucleoprotein granule (GO:0035770)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
rRNA processing in the mitochondrion	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
mRNA metabolic process	2
RNA modification	2
mitochondrion	2
mitochondrial translation	1
positive regulation of translation	1
regulation of mitochondrial translation	1
tRNA pseudouridine synthesis	1
mitochondrial tRNA modification	1
pseudouridine synthesis	1
mRNA modification	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
tRNA metabolic process	1
RNA metabolic process	1
macromolecule modification	1
nucleic acid binding	1
intramolecular transferase activity	1
tRNA pseudouridine synthase activity	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1
intracellular membraneless organelle	1
supramolecular complex	1

Protein interactions and networks

STRING

2750 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRUB2	DKC1	O60832	862
TRUB2	RPUSD3	Q6P087	842
TRUB2	RPUSD4	Q96CM3	835
TRUB2	PUS7L	Q9H0K6	810
TRUB2	NGRN	Q9NPE2	784
TRUB2	PUS10	Q3MIT2	754
TRUB2	PUS1	Q9Y606	751
TRUB2	RPUSD2	Q8IZ73	749
TRUB2	PUS7	Q96PZ0	737
TRUB2	PUS3	Q9BZE2	717
TRUB2	PUSL1	Q8N0Z8	714
TRUB2	RPUSD1	Q9UJJ7	707
TRUB2	GTPBP10	A4D1E9	647
TRUB2	MTERF3	Q96E29	638
TRUB2	FASTKD2	Q9NYY8	626

IntAct

123 interactions, top by confidence:

A	B	Type	Score
RCC1L	NME6	psi-mi:“MI:0914”(association)	0.720
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
FAM120A	SYNCRIP	psi-mi:“MI:0914”(association)	0.640
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
MRPL50	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
RBMX	PTCD1	psi-mi:“MI:0914”(association)	0.530
DDX28	PTCD1	psi-mi:“MI:0914”(association)	0.530
TRUB2	HSPD1	psi-mi:“MI:0914”(association)	0.530
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
FBXW11	AHCYL1	psi-mi:“MI:0914”(association)	0.530
HNRNPA1	PTCD1	psi-mi:“MI:0914”(association)	0.530
IGF2BP3	PTCD1	psi-mi:“MI:0914”(association)	0.530
MRPL13	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
UQCRFS1	NDUFAB1	psi-mi:“MI:0914”(association)	0.530

BioGRID (435): TRUB2 (Affinity Capture-MS), TRUB2 (Affinity Capture-MS), TRUB2 (Affinity Capture-MS), TRUB2 (Affinity Capture-MS), TRUB2 (Affinity Capture-MS), FYCO1 (Affinity Capture-MS), YARS2 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), DCAF10 (Affinity Capture-MS), MRPL39 (Affinity Capture-MS), TRUB2 (Affinity Capture-MS), TRUB2 (Affinity Capture-MS), TRUB2 (Affinity Capture-MS), TRUB2 (Affinity Capture-MS), TRUB2 (Affinity Capture-MS)

ESM2 similar proteins: A5D7Q3, A7MBC2, D3ZEY4, E7F654, E9QAM5, F1S5L4, O43824, O95822, O95900, P13233, P23249, P41229, P41230, P53167, P53370, P70563, P97564, Q14BI7, Q28C60, Q2KI24, Q2M296, Q2NKY8, Q38JA7, Q3MHU3, Q52L34, Q5BJS0, Q5F259, Q5GJ77, Q5R607, Q5XFW2, Q5XGG2, Q5ZI74, Q61586, Q6DBR0, Q6DCK1, Q6P5E8, Q7L2E3, Q8CH40, Q8NDG6, Q8T773

Diamond homologs: A6LLV6, O59721, O95900, Q5M934, Q5XFW2, Q5XGG2, Q8C0D0, Q8WWH5, Q91WG3, Q2SML1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 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
Mitochondrial ribosome-associated quality control	14	22.3×	4e-13
Mitochondrial translation	12	21.4×	2e-11
Mitochondrial translation initiation	13	21.4×	3e-12
Mitochondrial translation elongation	13	21.4×	3e-12
Mitochondrial translation termination	13	18.5×	1e-11
mRNA 3’-end processing	5	12.8×	1e-03
Transport of Mature mRNA derived from an Intron-Containing Transcript	6	11.9×	4e-04
Processing of Capped Intron-Containing Pre-mRNA	10	10.7×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial large ribosomal subunit assembly	5	49.1×	4e-06
positive regulation of cytoplasmic translation	5	49.1×	4e-06
mitochondrial translation	15	25.8×	8e-15
regulation of alternative mRNA splicing, via spliceosome	8	19.4×	1e-06
mRNA transport	5	13.0×	1e-03
negative regulation of translation	6	11.6×	6e-04
RNA processing	5	10.8×	3e-03
translation	10	10.2×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

944 predictions. Top by Δscore:

Variant	Effect	Δscore
9:128309704:T:TA	donor_gain	1.0000
9:128309876:C:CC	acceptor_gain	1.0000
9:128309880:C:CT	acceptor_gain	1.0000
9:128310882:CCTA:C	donor_loss	1.0000
9:128310884:TAC:T	donor_loss	1.0000
9:128310886:C:A	donor_loss	1.0000
9:128311525:T:TA	donor_loss	1.0000
9:128311526:CACAT:C	donor_loss	1.0000
9:128311527:A:AC	donor_gain	1.0000
9:128311528:C:CC	donor_gain	1.0000
9:128311528:CAT:C	donor_gain	1.0000
9:128311528:CATCA:C	donor_gain	1.0000
9:128311598:TGGT:T	acceptor_gain	1.0000
9:128311599:GGT:G	acceptor_gain	1.0000
9:128311600:GT:G	acceptor_gain	1.0000
9:128311601:TC:T	acceptor_loss	1.0000
9:128311602:C:CC	acceptor_gain	1.0000
9:128311603:T:A	acceptor_loss	1.0000
9:128313796:T:TA	donor_gain	1.0000
9:128313797:C:A	donor_gain	1.0000
9:128313806:A:AC	donor_gain	1.0000
9:128313807:C:CC	donor_gain	1.0000
9:128313887:ATCCT:A	acceptor_loss	1.0000
9:128313888:TC:T	acceptor_gain	1.0000
9:128313889:CC:C	acceptor_gain	1.0000
9:128313890:CTTCA:C	acceptor_loss	1.0000
9:128313891:T:G	acceptor_loss	1.0000
9:128313893:C:CT	acceptor_gain	1.0000
9:128313899:C:CT	acceptor_gain	1.0000
9:128317227:C:CC	acceptor_gain	1.0000

AlphaMissense

2134 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128309818:C:T	G243D	0.989
9:128317160:C:T	G103E	0.987
9:128309776:C:G	R257P	0.986
9:128322358:C:A	K17N	0.984
9:128322358:C:G	K17N	0.984
9:128309790:G:C	C252W	0.983
9:128309809:A:G	L246P	0.983
9:128309726:A:G	W274R	0.981
9:128309726:A:T	W274R	0.981
9:128309770:C:G	R259P	0.981
9:128309777:G:T	R257S	0.981
9:128309797:G:T	A250D	0.981
9:128310895:A:G	F221S	0.981
9:128309798:C:G	A250P	0.979
9:128313873:C:T	G132D	0.979
9:128309792:A:G	C252R	0.978
9:128309819:C:G	G243R	0.978
9:128309830:A:T	V239D	0.978
9:128309779:C:G	R256P	0.977
9:128317160:C:A	G103V	0.977
9:128313874:C:G	G132R	0.976
9:128313859:C:G	A137P	0.975
9:128313864:C:T	G135D	0.975
9:128310894:G:C	F221L	0.972
9:128310894:G:T	F221L	0.972
9:128310896:A:G	F221L	0.972
9:128309865:G:C	C227W	0.971
9:128313864:C:A	G135V	0.971
9:128309791:C:T	C252Y	0.968
9:128317161:C:G	G103R	0.967

dbSNP variants (sampled 300 via entrez): RS1000053586 (9:128313390 G>T), RS1000240845 (9:128323042 G>A), RS1000315946 (9:128323258 A>G), RS1000453421 (9:128318342 C>T), RS1000500530 (9:128318567 T>C), RS1000578493 (9:128324245 T>C), RS1000747808 (9:128306597 G>A), RS1000748186 (9:128324068 C>T), RS1001048484 (9:128306403 T>G), RS1001219617 (9:128305984 C>T), RS1001238479 (9:128319142 T>C), RS1001350510 (9:128322807 C>T), RS1001455986 (9:128316763 G>A), RS1001506887 (9:128317126 AC>A), RS1001821971 (9:128305466 A>G)

Disease associations

OMIM: gene MIM:610727 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_186	Obesity-related traits	7.000000e-06
GCST001762_726	Obesity-related traits	6.000000e-06
GCST005951_65	Body mass index	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
GSK-J4	decreases expression	1
chloroacetaldehyde	affects expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
jinfukang	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Doxorubicin	affects expression	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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