TSR3

Summary

TSR3 (TSR3 ribosome maturation factor, HGNC:14175) is a protein-coding gene on chromosome 16p13.3, encoding 18S rRNA aminocarboxypropyltransferase (Q9UJK0). Aminocarboxypropyltransferase that catalyzes the aminocarboxypropyl transfer on pseudouridine at position 1248 (Psi1248) in 18S rRNA.

Enables rRNA small subunit aminocarboxypropyltransferase activity. Involved in enzyme-directed rRNA pseudouridine synthesis. Predicted to be located in cytosol.

Source: NCBI Gene 115939 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 66 total — 1 pathogenic
• MANE Select transcript: NM_001001410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14175
Approved symbol	TSR3
Name	TSR3 ribosome maturation factor
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC24381
Ensembl gene	ENSG00000007520
Ensembl biotype	protein_coding
OMIM	617058
Entrez	115939

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000007390, ENST00000566296, ENST00000858635, ENST00000911396, ENST00000956793, ENST00000956794

RefSeq mRNA: 1 — MANE Select: NM_001001410 NM_001001410

CCDS: CCDS10435

Canonical transcript exons

ENST00000007390 — 6 exons

Exon	Start	End
ENSE00000346153	1351379	1351598
ENSE00000665570	1351693	1351878
ENSE00000665596	1349889	1349952
ENSE00001062114	1349240	1349608
ENSE00003595524	1350058	1350234
ENSE00003606439	1350807	1351000

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.7893 / max 118.9985, expressed in 1802 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155837	17.7893	1802

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.17	gold quality
apex of heart	UBERON:0002098	97.19	gold quality
cervix squamous epithelium	UBERON:0006922	95.51	gold quality
medial globus pallidus	UBERON:0002477	95.01	gold quality
heart left ventricle	UBERON:0002084	94.95	gold quality
mucosa of transverse colon	UBERON:0004991	94.94	gold quality
cardiac ventricle	UBERON:0002082	94.71	gold quality
putamen	UBERON:0001874	94.58	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.51	gold quality
amygdala	UBERON:0001876	94.47	gold quality
gastrocnemius	UBERON:0001388	94.45	gold quality
right atrium auricular region	UBERON:0006631	94.40	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.40	gold quality
nucleus accumbens	UBERON:0001882	94.29	gold quality
left coronary artery	UBERON:0001626	94.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.22	gold quality
lower esophagus	UBERON:0013473	94.21	gold quality
muscle of leg	UBERON:0001383	94.15	gold quality
gingival epithelium	UBERON:0001949	94.02	gold quality
coronary artery	UBERON:0001621	93.98	gold quality
right frontal lobe	UBERON:0002810	93.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.92	gold quality
caudate nucleus	UBERON:0001873	93.87	gold quality
prefrontal cortex	UBERON:0000451	93.80	gold quality
right coronary artery	UBERON:0001625	93.74	gold quality
body of stomach	UBERON:0001161	93.73	gold quality
thoracic aorta	UBERON:0001515	93.62	gold quality
ascending aorta	UBERON:0001496	93.61	gold quality
cardiac atrium	UBERON:0002081	93.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.71
E-GEOD-83139	no	3.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting TSR3, 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-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-517-5P	97.13	68.43	781

Literature-anchored findings (GeneRIF, showing 1)

• Structurally, Tsr3 represents a novel class of acp transferase enzymes. (PMID:27084949)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tsr3	ENSDARG00000038567
mus_musculus	Tsr3	ENSMUSG00000015126
rattus_norvegicus	Tsr3	ENSRNOG00000017858
drosophila_melanogaster	CG4338	FBGN0038313
caenorhabditis_elegans		WBGENE00018679

Protein

Protein identifiers

18S rRNA aminocarboxypropyltransferase — Q9UJK0 (reviewed: Q9UJK0)

Alternative names: 20S S rRNA accumulation protein 3 homolog

All UniProt accessions (2): Q9UJK0, H3BQD4

UniProt curated annotations — full annotation on UniProt →

Function. Aminocarboxypropyltransferase that catalyzes the aminocarboxypropyl transfer on pseudouridine at position 1248 (Psi1248) in 18S rRNA. It constitutes the last step in biosynthesis of the hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) conserved in eukaryotic 18S rRNA.

Subcellular location. Cytoplasm.

Similarity. Belongs to the TDD superfamily. TSR3 family.

RefSeq proteins (1): NP_001001410* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007177	Tsr3_C	Domain
IPR007209	RNaseL-inhib-like_metal-bd_dom	Domain
IPR022968	Tsr3-like	Family

Pfam: PF04034, PF04068

Catalyzed reactions (Rhea), 2 shown:

• N(1)-methylpseudouridine(1248) in human 18S rRNA + S-adenosyl-L-methionine = N(1)-methyl-N(3)-[(3S)-3-amino-3-carboxypropyl]pseudouridine(1248) in human 18S rRNA + S-methyl-5’-thioadenosine + H(+) (RHEA:63292)
• an N(1)-methylpseudouridine in rRNA + S-adenosyl-L-methionine = N(1)-methyl-N(3)-[(3S)-3-amino-3-carboxypropyl]pseudouridine in rRNA + S-methyl-5’-thioadenosine + H(+) (RHEA:63296)

UniProt features (12 total): modified residue 5, binding site 4, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJK0-F1	75.17	0.49

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 (4): 74; 122; 145; 160

Post-translational modifications (5): 264, 282, 24, 259, 261

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol

MSigDB gene sets: 119 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA, GOBP_PSEUDOURIDINE_SYNTHESIS, GOBP_RNA_MODIFICATION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, MORF_PPP2R4, ACEVEDO_LIVER_CANCER_UP, GOBP_RRNA_MODIFICATION, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, REACTOME_METABOLISM_OF_RNA, OSMAN_BLADDER_CANCER_DN, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GOMF_SULFUR_COMPOUND_BINDING, YAGI_AML_WITH_T_8_21_TRANSLOCATION

GO Biological Process (5): rRNA modification (GO:0000154), enzyme-directed rRNA pseudouridine synthesis (GO:0000455), maturation of SSU-rRNA (GO:0030490), rRNA processing (GO:0006364), ribosome biogenesis (GO:0042254)

GO Molecular Function (3): transferase activity (GO:0016740), rRNA small subunit aminocarboxypropyltransferase activity (GO:0106388), S-adenosyl-L-methionine binding (GO:1904047)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
rRNA processing	2
cellular anatomical structure	2
RNA modification	1
rRNA pseudouridine synthesis	1
ribosomal small subunit biogenesis	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
ribonucleoprotein complex biogenesis	1
catalytic activity	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
catalytic activity, acting on a rRNA	1
cation binding	1
sulfur compound binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSR3	TSR2	Q969E8	847
TSR3	TSR1	Q2NL82	810
TSR3	DTWD2	Q8NBA8	733
TSR3	EMG1	Q92979	718
TSR3	TYW2	Q53H54	710
TSR3	DTWD1	Q8N5C7	709
TSR3	POFUT2	Q9Y2G5	694
TSR3	CFP	P27918	659
TSR3	DPY19L3	Q6ZPD9	615
TSR3	BUD23	O43709	593
TSR3	OR2B3	O76000	583
TSR3	NOB1	Q9ULX3	572
TSR3	SLC35F4	A4IF30	544
TSR3	DPY19L1	Q2PZI1	540
TSR3	ANTKMT	Q9BQD7	531

IntAct

66 interactions, top by confidence:

A	B	Type	Score
FOSL2	JUN	psi-mi:“MI:0914”(association)	0.930
MTMR7	CCNH	psi-mi:“MI:0914”(association)	0.740
FOSB	JUN	psi-mi:“MI:0914”(association)	0.690
REL	NFKBIE	psi-mi:“MI:0914”(association)	0.670
CCND1	CDK1	psi-mi:“MI:0914”(association)	0.640
GOLPH3	RCC1L	psi-mi:“MI:0914”(association)	0.640
FGL1	LCMT2	psi-mi:“MI:0914”(association)	0.640
OSER1	LACC1	psi-mi:“MI:0914”(association)	0.620
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
CACNG5	ZNF316	psi-mi:“MI:0914”(association)	0.530
CFAP46	GAPDHS	psi-mi:“MI:0914”(association)	0.530
MAF1	POLR3A	psi-mi:“MI:0914”(association)	0.530
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
FOSL2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	SIAH2	psi-mi:“MI:0914”(association)	0.530
TPCN2	AP3B1	psi-mi:“MI:0914”(association)	0.530
SAMTOR	PER1	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	METTL18	psi-mi:“MI:0914”(association)	0.530
MEF2A	TSR3	psi-mi:“MI:0915”(physical association)	0.400
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Srp72		psi-mi:“MI:0914”(association)	0.350

BioGRID (68): TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS), TSR3 (Affinity Capture-MS)

ESM2 similar proteins: A1L131, A8MXQ7, C0HAV3, C5IJB0, D3ZND0, F1MX48, O54935, O60232, O95400, P18887, P36916, P56873, Q15527, Q17QX2, Q27J81, Q28H71, Q2KIJ6, Q2YD98, Q32KW2, Q3SYU1, Q3ZBN4, Q5FVK6, Q5HZH2, Q5PPF5, Q5T0F9, Q5U4Z3, Q60596, Q6MG06, Q7T0L4, Q8BIY1, Q8BRN9, Q8N5A5, Q8VDM1, Q8WVB6, Q8WVT3, Q91VL8, Q924T7, Q96EP0, Q99JB7, Q99PL6

Diamond homologs: A5UJF3, B0R700, C3MQM6, C3MWA4, C3N6E6, C3NEV4, C3NGU0, C4KHW1, E1QU22, O26654, Q10409, Q12094, Q12ZL9, Q2NET3, Q469W0, Q58118, Q5HZH2, Q8PSK5, Q8TMY6, Q8TXM4, Q975W6, Q97CM6, Q9HM46, Q9HNJ6, Q9UJK0, Q9UWV6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	46
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2425969	NC_000016.9:g.(?256302)(1657267_?)del	Pathogenic

SpliceAI

633 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1349959:C:CT	acceptor_gain	1.0000
16:1349960:G:T	acceptor_gain	1.0000
16:1350053:CTCA:C	donor_loss	1.0000
16:1350054:TCA:T	donor_loss	1.0000
16:1350055:CA:C	donor_loss	1.0000
16:1350056:A:AC	donor_gain	1.0000
16:1350057:C:CC	donor_gain	1.0000
16:1350057:CCGAT:C	donor_gain	1.0000
16:1350066:T:TA	donor_gain	1.0000
16:1350069:T:TA	donor_gain	1.0000
16:1350081:T:A	donor_gain	1.0000
16:1350204:C:CT	acceptor_gain	1.0000
16:1350231:AAGC:A	acceptor_gain	1.0000
16:1350235:C:CC	acceptor_gain	1.0000
16:1350235:CT:C	acceptor_loss	1.0000
16:1350802:CTCA:C	donor_loss	1.0000
16:1350805:A:AC	donor_gain	1.0000
16:1350805:A:C	donor_loss	1.0000
16:1350806:C:CC	donor_gain	1.0000
16:1350806:CCTA:C	donor_gain	1.0000
16:1350997:CTGT:C	acceptor_gain	1.0000
16:1351005:C:CT	acceptor_gain	1.0000
16:1351376:TACCT:T	donor_loss	1.0000
16:1351378:CC:C	donor_loss	1.0000
16:1351378:CCTGT:C	donor_gain	1.0000
16:1351688:CTCA:C	donor_loss	1.0000
16:1351689:TCACC:T	donor_loss	1.0000
16:1351690:CA:C	donor_loss	1.0000
16:1351691:A:AC	donor_gain	1.0000
16:1351691:AC:A	donor_gain	1.0000

AlphaMissense

2000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1350197:A:C	F188L	0.997
16:1350197:A:T	F188L	0.997
16:1350199:A:G	F188L	0.997
16:1350955:C:A	W126C	0.996
16:1350955:C:G	W126C	0.996
16:1351522:C:A	W63C	0.996
16:1351522:C:G	W63C	0.996
16:1350191:C:A	W190C	0.995
16:1350191:C:G	W190C	0.995
16:1350180:A:G	F194S	0.994
16:1350193:A:G	W190R	0.994
16:1350193:A:T	W190R	0.994
16:1350835:T:A	E166D	0.993
16:1350835:T:G	E166D	0.993
16:1350836:T:A	E166V	0.993
16:1350179:G:C	F194L	0.992
16:1350179:G:T	F194L	0.992
16:1350181:A:G	F194L	0.992
16:1351524:A:G	W63R	0.992
16:1351524:A:T	W63R	0.992
16:1350884:G:T	A150D	0.991
16:1350957:A:G	W126R	0.991
16:1350957:A:T	W126R	0.991
16:1351432:G:C	F93L	0.991
16:1351432:G:T	F93L	0.991
16:1351434:A:G	F93L	0.991
16:1350968:A:T	I122N	0.990
16:1350974:G:T	A120D	0.990
16:1350877:G:C	N152K	0.989
16:1350877:G:T	N152K	0.989

dbSNP variants (sampled 300 via entrez): RS1000826301 (16:1350444 T>A), RS1000935039 (16:1351074 A>C), RS1001218165 (16:1352691 G>A), RS1001607169 (16:1352982 T>TC), RS1001709426 (16:1350866 T>C,G), RS1001715643 (16:1348964 G>A,T), RS1003116954 (16:1351908 G>T), RS1003337137 (16:1350044 C>A,T), RS1004044382 (16:1351787 T>C,G), RS1004055677 (16:1351583 C>A,T), RS1005015597 (16:1350770 C>T), RS1005211601 (16:1350701 G>A,T), RS1006130223 (16:1352624 CT>C,CTT), RS1006329439 (16:1351922 G>A,C), RS1007240454 (16:1351297 C>G)

Disease associations

OMIM: gene MIM:617058 | disease phenotypes: MIM:266920

GenCC curated gene-disease

Mondo (1): short-rib thoracic dysplasia 9 with or without polydactyly (MONDO:0009964)

Orphanet (1): Saldino-Mainzer syndrome (Orphanet:140969)

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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, decreases reaction, decreases expression, increases expression	3
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	increases expression	1
Atrazine	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	increases expression	1
Ribonucleotides	affects binding, decreases reaction	1
Selenium	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Vitamin E	increases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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