TRIR

Summary

TRIR (telomerase RNA component interacting RNase, HGNC:28424) is a protein-coding gene on chromosome 19p13.13, encoding Telomerase RNA component interacting RNase (Q9BQ61). Exoribonuclease that is part of the telomerase RNA 3’ end processing complex and which has the ability to cleave all four unpaired RNA nucleotides from the 5’ end or 3’ end with higher efficiency for purine bases. It is a selective cancer dependency (DepMap: 12.5% of cell lines).

Enables 3’-5’ exonuclease activity and 5’-3’ exonuclease activity. Involved in rRNA catabolic process.

Source: NCBI Gene 79002 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• Cancer dependency (DepMap): dependent in 12.5% of screened cell lines
• MANE Select transcript: NM_024038

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28424
Approved symbol	TRIR
Name	telomerase RNA component interacting RNase
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC2803, fSAP18, TERCIR
Ensembl gene	ENSG00000123144
Ensembl biotype	protein_coding
Entrez	79002

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000242784, ENST00000588213, ENST00000589590, ENST00000591254, ENST00000592273

RefSeq mRNA: 3 — MANE Select: NM_024038 NM_001329738, NM_001329739, NM_024038

CCDS: CCDS12279, CCDS86709, CCDS86710

Canonical transcript exons

ENST00000242784 — 3 exons

Exon	Start	End
ENSE00002856959	12734313	12734684
ENSE00003584888	12731344	12731421
ENSE00003609336	12730640	12731068

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 190.8263 / max 4313.6949, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179352	189.1028	1828
179351	1.7235	978

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.12	gold quality
upper arm skin	UBERON:0004263	99.06	gold quality
kidney epithelium	UBERON:0004819	99.00	gold quality
cortical plate	UBERON:0005343	98.99	gold quality
embryo	UBERON:0000922	98.98	gold quality
ganglionic eminence	UBERON:0004023	98.98	gold quality
mucosa of transverse colon	UBERON:0004991	98.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.89	gold quality
endocervix	UBERON:0000458	98.83	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.80	gold quality
leukocyte	CL:0000738	98.79	gold quality
lower esophagus	UBERON:0013473	98.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.79	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.78	gold quality
monocyte	CL:0000576	98.77	gold quality
skin of abdomen	UBERON:0001416	98.76	gold quality
left ovary	UBERON:0002119	98.75	gold quality
parotid gland	UBERON:0001831	98.74	gold quality
ileal mucosa	UBERON:0000331	98.73	gold quality
body of uterus	UBERON:0009853	98.73	gold quality
right ovary	UBERON:0002118	98.71	gold quality
body of stomach	UBERON:0001161	98.70	gold quality
spleen	UBERON:0002106	98.69	gold quality
transverse colon	UBERON:0001157	98.68	gold quality
skin of leg	UBERON:0001511	98.68	gold quality
right lobe of liver	UBERON:0001114	98.67	gold quality
left uterine tube	UBERON:0001303	98.67	gold quality
ectocervix	UBERON:0012249	98.67	gold quality
lower esophagus mucosa	UBERON:0035834	98.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	196.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting TRIR, 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-6851-5P	100.00	65.63	1294
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-3690	96.44	65.18	737

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.5% of screened cell lines.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	trir	ENSDARG00000104178
mus_musculus	Trir	ENSMUSG00000041203
rattus_norvegicus	Trir	ENSRNOG00000003863

Protein

Protein identifiers

Telomerase RNA component interacting RNase — Q9BQ61 (reviewed: Q9BQ61)

Alternative names: Exoribonuclease TRIR

All UniProt accessions (4): K7ELS0, K7EN60, K7ERU7, Q9BQ61

UniProt curated annotations — full annotation on UniProt →

Function. Exoribonuclease that is part of the telomerase RNA 3’ end processing complex and which has the ability to cleave all four unpaired RNA nucleotides from the 5’ end or 3’ end with higher efficiency for purine bases.

Subunit / interactions. Part of the telomerase RNA 3’ end complex which contains about 488 proteins.

Activity regulation. Zn(2+) inhibits the RNase activity while Mg(2+), Ca(2+), Mn(2+), K(+), Na(+), EDTA and EGTA show little effect on the exoribonuclease activity.

Domain organisation. The C-terminus contains a key domain which is responsible for the RNA digestion activity.

RefSeq proteins (3): NP_001316667, NP_001316668, NP_076943* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038838	TRIR	Family

UniProt features (7 total): compositionally biased region 4, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQ61-F1	63.56	0.07

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 (1): 146

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): E2F_Q4_01, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOMF_NUCLEASE_ACTIVITY, GCANCTGNY_MYOD_Q6, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GGGTGGRR_PAX4_03, RICKMAN_METASTASIS_DN, E2F_Q3, E2F1_Q3, GOMF_EXONUCLEASE_ACTIVITY, GOBP_RRNA_CATABOLIC_PROCESS, E2F_Q6_01, ATGTACA_MIR493, TCCCRNNRTGC_UNKNOWN

GO Biological Process (1): rRNA catabolic process (GO:0016075)

GO Molecular Function (7): RNA binding (GO:0003723), 3’-5’ exonuclease activity (GO:0008408), 5’-3’ exonuclease activity (GO:0008409), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
exonuclease activity	2
RNA catabolic process	1
rRNA metabolic process	1
nucleic acid binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

1458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIR	TRIL	Q7L0X0	706
TRIR	UBB	P02248	547
TRIR	RPL36	Q9Y3U8	546
TRIR	SF3A2	Q15428	545
TRIR	EPHX3	Q9H6B9	510
TRIR	NCLN	Q969V3	496
TRIR	DDX55	Q8NHQ9	491
TRIR	UBB	P02248	484
TRIR	SNRPA	P09012	483
TRIR	ISOC2	Q96AB3	409
TRIR	ZSWIM1	Q9BR11	400
TRIR	REX1BD	Q96EN9	396
TRIR	DPM3	Q9P2X0	395
TRIR	TRMO	Q9BU70	372
TRIR	NDUFAF8	A1L188	357

IntAct

51 interactions, top by confidence:

A	B	Type	Score
SNRPA	TRIR	psi-mi:“MI:0915”(physical association)	0.740
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SF3A2	TRIR	psi-mi:“MI:0915”(physical association)	0.400
ERBB3	TRIR	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PCIF1	POLR2A	psi-mi:“MI:0914”(association)	0.350
Junb	RGPD3	psi-mi:“MI:0914”(association)	0.350
EMC2	TBL2	psi-mi:“MI:0914”(association)	0.350
MMGT1	DERL1	psi-mi:“MI:0914”(association)	0.350
SLC33A1	METTL8	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
PRKD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
CD81	CD276	psi-mi:“MI:0914”(association)	0.350
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
TRIR	EMB	psi-mi:“MI:0914”(association)	0.350
RBM17	HSPA8	psi-mi:“MI:0914”(association)	0.350
U2SURP	PPM1G	psi-mi:“MI:0914”(association)	0.350
SLC32A1	SMCHD1	psi-mi:“MI:0914”(association)	0.350
SLC35F4	SHTN1	psi-mi:“MI:0914”(association)	0.350
SF3B1	RBM10	psi-mi:“MI:0914”(association)	0.350
SF3B1	FAM83G	psi-mi:“MI:0914”(association)	0.350
STAT3	NACA	psi-mi:“MI:0914”(association)	0.350
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (76): C19orf43 (Two-hybrid), AIMP1 (Co-fractionation), C19orf43 (Affinity Capture-MS), C19orf43 (Affinity Capture-MS), C19orf43 (Affinity Capture-MS), C19orf43 (Affinity Capture-MS), C19orf43 (Affinity Capture-MS), C19orf43 (Affinity Capture-MS), C19orf43 (Affinity Capture-MS), C19orf43 (Affinity Capture-MS), C19orf43 (Affinity Capture-MS), C19orf43 (Affinity Capture-MS), C19orf43 (Proximity Label-MS), C19orf43 (Two-hybrid), C19orf43 (Proximity Label-MS)

ESM2 similar proteins: A4D2P6, A5PJV8, A6NFD8, D4AE48, O00268, O00287, O35274, O35779, O43566, P04198, P12755, P55199, Q08DA0, Q0D2I5, Q2KJ58, Q504T8, Q5XKK7, Q60698, Q61976, Q6NZ67, Q6P582, Q6R891, Q6T4P5, Q7Z6J2, Q80YR4, Q86UD0, Q86UK7, Q8BXL9, Q8CEG5, Q8R4T5, Q8TF61, Q8VCG9, Q969F2, Q969G9, Q96HZ4, Q96SB3, Q99PV5, Q9BQ61, Q9BUN5, Q9BZE9

Diamond homologs: Q9BQ61, Q9D735

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 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
mRNA Splicing	11	29.5×	4e-12
Processing of Capped Intron-Containing Pre-mRNA	14	28.1×	3e-15
mRNA Polyadenylation	13	27.9×	4e-14
mRNA Splicing - Minor Pathway	5	27.3×	4e-05
mRNA Splicing - Major Pathway	17	22.7×	5e-17
CHD1 and CHD2 subfamily	6	15.9×	7e-05
Dengue Virus-Host Interactions	14	15.6×	5e-12
Metabolism of RNA	11	11.2×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	10	17.3×	1e-07
mRNA processing	9	13.4×	5e-06
RNA splicing	6	10.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

415 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12731064:AATAC:A	acceptor_gain	1.0000
19:12731065:ATAC:A	acceptor_gain	1.0000
19:12731066:TAC:T	acceptor_gain	1.0000
19:12731067:AC:A	acceptor_gain	1.0000
19:12731068:CC:C	acceptor_gain	1.0000
19:12731069:C:A	acceptor_loss	1.0000
19:12731069:C:CC	acceptor_gain	1.0000
19:12731070:T:G	acceptor_loss	1.0000
19:12731338:GCTCA:G	donor_loss	1.0000
19:12731339:CTCA:C	donor_loss	1.0000
19:12731340:TCAC:T	donor_loss	1.0000
19:12731341:CA:C	donor_loss	1.0000
19:12731342:ACCTC:A	donor_loss	1.0000
19:12734311:A:AC	donor_gain	1.0000
19:12734312:C:CC	donor_gain	1.0000
19:12734312:CGAAG:C	donor_gain	1.0000
19:12734342:T:TA	donor_gain	1.0000
19:12734413:T:TA	donor_gain	1.0000
19:12731342:A:AC	donor_gain	0.9900
19:12731343:C:CC	donor_gain	0.9900
19:12731420:ACC:A	acceptor_loss	0.9900
19:12731421:CCTG:C	acceptor_loss	0.9900
19:12731422:C:CA	acceptor_loss	0.9900
19:12731423:T:G	acceptor_loss	0.9900
19:12734308:CTTA:C	donor_loss	0.9900
19:12734309:TTA:T	donor_loss	0.9900
19:12734310:TACGA:T	donor_loss	0.9900
19:12734311:ACGAA:A	donor_loss	0.9900
19:12734312:CG:C	donor_gain	0.9900
19:12734312:CGA:C	donor_gain	0.9900

AlphaMissense

1123 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12730971:A:G	L174P	1.000
19:12730971:A:T	L174Q	1.000
19:12730999:A:G	C165R	1.000
19:12731009:T:A	K161N	1.000
19:12731009:T:G	K161N	1.000
19:12731013:T:C	Y160C	1.000
19:12731013:T:G	Y160S	1.000
19:12731014:A:C	Y160D	1.000
19:12731014:A:G	Y160H	1.000
19:12731022:A:G	V157A	1.000
19:12731023:C:A	V157L	1.000
19:12731023:C:G	V157L	1.000
19:12731023:C:T	V157M	1.000
19:12731024:T:A	E156D	1.000
19:12731024:T:G	E156D	1.000
19:12731026:C:T	E156K	1.000
19:12731029:C:G	A155P	1.000
19:12731034:T:C	Y153C	1.000
19:12731034:T:G	Y153S	1.000
19:12731035:A:C	Y153D	1.000
19:12731035:A:G	Y153H	1.000
19:12731035:A:T	Y153N	1.000
19:12731042:C:A	W150C	1.000
19:12731042:C:G	W150C	1.000
19:12731043:C:G	W150S	1.000
19:12731044:A:G	W150R	1.000
19:12731044:A:T	W150R	1.000
19:12731365:C:A	K134N	1.000
19:12731365:C:G	K134N	1.000
19:12731378:C:A	G130V	1.000

dbSNP variants (sampled 300 via entrez): RS1000278000 (19:12732795 G>A,T), RS1000389236 (19:12733966 G>C), RS1000879915 (19:12731445 C>A), RS1001663408 (19:12735402 C>T), RS1001706220 (19:12732080 C>A), RS1002117352 (19:12732420 C>T), RS1002134151 (19:12735096 A>C), RS1002201453 (19:12736370 C>T), RS1002449628 (19:12735627 G>A,T), RS1002549869 (19:12732057 G>A), RS1002833161 (19:12731696 C>G,T), RS1003103911 (19:12730714 CAGAA>C), RS1003628453 (19:12735238 C>A,T), RS1003788957 (19:12730563 C>T), RS1004371642 (19:12733006 C>T)

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

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Vorinostat	decreases expression	1
Cadmium	increases abundance, increases expression	1
Demecolcine	decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Ivermectin	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Vincristine	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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