RPUSD2

Summary

RPUSD2 (RNA pseudouridine synthase domain containing 2, HGNC:24180) is a protein-coding gene on chromosome 15q15.1, encoding Pseudouridylate synthase RPUSD2 (Q8IZ73). Pseudouridine synthase that catalyzes pseudouridylation of mRNAs.

Enables pseudouridine synthase activity. Involved in mRNA pseudouridine synthesis.

Source: NCBI Gene 27079 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_152260

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24180
Approved symbol	RPUSD2
Name	RNA pseudouridine synthase domain containing 2
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	C18B11, FLJ31409, PUS9
Ensembl gene	ENSG00000166133
Ensembl biotype	protein_coding
Entrez	27079

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000315616, ENST00000559271, ENST00000616318, ENST00000890562, ENST00000890563, ENST00000917964

RefSeq mRNA: 2 — MANE Select: NM_152260 NM_001286407, NM_152260

CCDS: CCDS10061, CCDS66737

Canonical transcript exons

ENST00000315616 — 3 exons

Exon	Start	End
ENSE00001100092	40571604	40571900
ENSE00001254269	40569299	40569943
ENSE00001834199	40573527	40574949

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 88.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0207 / max 47.4731, expressed in 1691 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146120	6.0207	1691

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	88.82	silver quality
secondary oocyte	CL:0000655	86.84	gold quality
paraflocculus	UBERON:0005351	86.60	gold quality
frontal pole	UBERON:0002795	86.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.73	gold quality
middle frontal gyrus	UBERON:0002702	84.47	silver quality
Brodmann (1909) area 10	UBERON:0013541	82.84	gold quality
gastrocnemius	UBERON:0001388	82.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.72	gold quality
muscle of leg	UBERON:0001383	81.25	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.77	gold quality
apex of heart	UBERON:0002098	80.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.66	gold quality
mucosa of transverse colon	UBERON:0004991	80.21	gold quality
stromal cell of endometrium	CL:0002255	78.87	gold quality
left adrenal gland cortex	UBERON:0035825	78.57	gold quality
granulocyte	CL:0000094	78.54	gold quality
left adrenal gland	UBERON:0001234	78.40	gold quality
right adrenal gland	UBERON:0001233	78.23	gold quality
heart left ventricle	UBERON:0002084	78.20	gold quality
prefrontal cortex	UBERON:0000451	78.03	gold quality
cardiac ventricle	UBERON:0002082	77.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.65	gold quality
right adrenal gland cortex	UBERON:0035827	77.63	gold quality
lower esophagus	UBERON:0013473	77.61	gold quality
muscle organ	UBERON:0001630	77.51	gold quality
gingival epithelium	UBERON:0001949	77.16	silver quality
oocyte	CL:0000023	77.13	gold quality
adrenal cortex	UBERON:0001235	77.09	gold quality
skin of leg	UBERON:0001511	77.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting RPUSD2, 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-4500	99.99	72.72	2367
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-3159	97.94	66.79	1098
HSA-MIR-1271-3P	97.56	64.85	865
HSA-MIR-550A-3-5P	97.56	65.35	823
HSA-MIR-550A-5P	97.56	65.35	823
HSA-MIR-3651	95.62	64.67	287

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpusd2	ENSDARG00000060992
mus_musculus	Rpusd2	ENSMUSG00000027324
rattus_norvegicus	Rpusd2	ENSRNOG00000010528
drosophila_melanogaster	RluA-2	FBGN0032256
drosophila_melanogaster	RluA-1	FBGN0051719
caenorhabditis_elegans		WBGENE00019498

Paralogs (3): RPUSD1 (ENSG00000007376), RPUSD3 (ENSG00000156990), RPUSD4 (ENSG00000165526)

Protein

Protein identifiers

Pseudouridylate synthase RPUSD2 — Q8IZ73 (reviewed: Q8IZ73)

Alternative names: RNA pseudouridylate synthase domain-containing protein 2

All UniProt accessions (2): A0A087WXE2, Q8IZ73

UniProt curated annotations — full annotation on UniProt →

Function. Pseudouridine synthase that catalyzes pseudouridylation of mRNAs.

Similarity. Belongs to the pseudouridine synthase RluA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IZ73-1	1	yes
Q8IZ73-2	2

RefSeq proteins (2): NP_001273336, NP_689473* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006145	PsdUridine_synth_RsuA/RluA	Domain
IPR006224	PsdUridine_synth_RluA-like_CS	Conserved_site
IPR006225	PsdUridine_synth_RluC/D	Family
IPR020103	PsdUridine_synth_cat_dom_sf	Homologous_superfamily
IPR050188	RluA_PseudoU_synthase	Family

Pfam: PF00849

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (9 total): sequence conflict 3, modified residue 2, chain 1, region of interest 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZ73-F1	76.03	0.57

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): 274

Post-translational modifications (2): 68, 477

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GOBP_RIBOSOME_BIOGENESIS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_MRNA_MODIFICATION, GOBP_PSEUDOURIDINE_SYNTHESIS, GOBP_RNA_MODIFICATION, HOEGERKORP_CD44_TARGETS_DIRECT_UP, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP, GOBP_RRNA_MODIFICATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_E2F4_UNSTIMULATED, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_UP, GOMF_PSEUDOURIDINE_SYNTHASE_ACTIVITY, GOMF_INTRAMOLECULAR_TRANSFERASE_ACTIVITY

GO Biological Process (5): enzyme-directed rRNA pseudouridine synthesis (GO:0000455), mRNA processing (GO:0006397), mRNA pseudouridine synthesis (GO:1990481), pseudouridine synthesis (GO:0001522), RNA modification (GO:0009451)

GO Molecular Function (3): RNA binding (GO:0003723), pseudouridine synthase activity (GO:0009982), isomerase activity (GO:0016853)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
rRNA pseudouridine synthesis	1
RNA processing	1
mRNA metabolic process	1
pseudouridine synthesis	1
mRNA modification	1
RNA modification	1
RNA metabolic process	1
macromolecule modification	1
nucleic acid binding	1
intramolecular transferase activity	1
catalytic activity	1

Protein interactions and networks

STRING

1815 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPUSD2	TRUB1	Q8WWH5	811
RPUSD2	PUS7	Q96PZ0	811
RPUSD2	PUS1	Q9Y606	806
RPUSD2	PUS7L	Q9H0K6	776
RPUSD2	PUS3	Q9BZE2	767
RPUSD2	PUS10	Q3MIT2	763
RPUSD2	TRUB2	O95900	749
RPUSD2	RPUSD3	Q6P087	715
RPUSD2	PUSL1	Q8N0Z8	584
RPUSD2	DKC1	O60832	557
RPUSD2	LCMT2	O60294	470
RPUSD2	TRMT112	Q9UI30	458
RPUSD2	QTRT2	Q9H974	456
RPUSD2	ASB3	Q9Y575	452
RPUSD2	PNO1	Q9NRX1	445

IntAct

22 interactions, top by confidence:

A	B	Type	Score
PFDN4	PFDN6	psi-mi:“MI:0914”(association)	0.730
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
CELA2B	AURKA	psi-mi:“MI:0914”(association)	0.530
PMPCA	CLUH	psi-mi:“MI:0914”(association)	0.530
ALDH8A1	ALDH6A1	psi-mi:“MI:0914”(association)	0.530
RPUSD2	GRB2	psi-mi:“MI:0915”(physical association)	0.400
NEU4	AIP	psi-mi:“MI:0914”(association)	0.350
SPATA8	PSMG1	psi-mi:“MI:0914”(association)	0.350
SHISA3	ZNF316	psi-mi:“MI:0914”(association)	0.350
	POLRMT	psi-mi:“MI:0914”(association)	0.350
SPATA8	GMFG	psi-mi:“MI:0914”(association)	0.350
NTNG1	UBA6	psi-mi:“MI:0914”(association)	0.350
DNAJB6	SCAMP1	psi-mi:“MI:0914”(association)	0.350
ARGLU1	PIAS2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (44): RPUSD2 (Affinity Capture-MS), RPUSD2 (Affinity Capture-MS), RPUSD2 (Co-fractionation), RPUSD2 (Co-fractionation), RPUSD2 (Co-fractionation), RPUSD2 (Reconstituted Complex), RPUSD2 (Affinity Capture-MS), RPUSD2 (Affinity Capture-MS), RPUSD2 (Affinity Capture-MS), RPUSD2 (Affinity Capture-MS), RPUSD2 (Affinity Capture-MS), RPUSD2 (Affinity Capture-MS), RPUSD2 (Affinity Capture-MS), RPUSD2 (Proximity Label-MS), RPUSD2 (Proximity Label-MS)

ESM2 similar proteins: A0A0K9RDW0, A1L4V7, A2Y8B9, A3BN26, A6NHR9, B4FTR7, B8B0E2, B9EYZ1, F4I933, F4J117, O35099, O49931, O81360, P03271, P03272, P03273, P93236, P93740, Q0DST9, Q0DVX2, Q0JCU7, Q0WL81, Q3U487, Q56X76, Q5E9N5, Q5M721, Q5QLS7, Q5T447, Q5VRY0, Q5VS72, Q60649, Q69TY5, Q6ATB4, Q6K9C1, Q6YSY5, Q7X745, Q8H4D4, Q8IZ73, Q8S2E5, Q8W519

Diamond homologs: O16686, O25610, O31613, O66114, O67638, P0AA37, P0AA38, P0AA39, P0AA40, P44445, P44782, P59831, P70870, P72970, Q09709, Q0E0Y3, Q12069, Q12362, Q149F1, Q45826, Q5M721, Q68XB2, Q87LD3, Q87N15, Q89AH2, Q8D8G1, Q8DCG0, Q8FIP7, Q8FL93, Q8IZ73, Q8X8J3, Q8XA10, Q8XYX8, Q8Z439, Q8Z9J5, Q8ZFU1, Q8ZIK1, Q8ZMD5, Q8ZQ16, Q8ZRV9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

282 predictions. Top by Δscore:

Variant	Effect	Δscore
15:40571600:ACAG:A	acceptor_loss	1.0000
15:40571602:A:AC	acceptor_loss	1.0000
15:40571896:GGCAG:G	donor_gain	1.0000
15:40571897:GCAG:G	donor_gain	1.0000
15:40571897:GCAGG:G	donor_gain	1.0000
15:40571899:AGGT:A	donor_loss	1.0000
15:40573522:T:G	acceptor_gain	1.0000
15:40573525:A:AG	acceptor_gain	1.0000
15:40573525:AGCT:A	acceptor_gain	1.0000
15:40573526:G:GG	acceptor_gain	1.0000
15:40573526:GCT:G	acceptor_gain	1.0000
15:40573526:GCTG:G	acceptor_gain	1.0000
15:40569980:G:GT	donor_gain	0.9900
15:40571598:T:TA	acceptor_gain	0.9900
15:40571602:A:AG	acceptor_gain	0.9900
15:40571602:AG:A	acceptor_gain	0.9900
15:40571603:G:GG	acceptor_gain	0.9900
15:40571603:GG:G	acceptor_gain	0.9900
15:40571603:GGA:G	acceptor_gain	0.9900
15:40571603:GGAC:G	acceptor_gain	0.9900
15:40571603:GGACA:G	acceptor_gain	0.9900
15:40571901:G:GG	donor_gain	0.9900
15:40571902:T:A	donor_loss	0.9900
15:40573521:AT:A	acceptor_gain	0.9900
15:40573522:T:TA	acceptor_gain	0.9900
15:40573524:TAGCT:T	acceptor_loss	0.9900
15:40573525:A:AC	acceptor_loss	0.9900
15:40573525:AGCTG:A	acceptor_gain	0.9900
15:40573526:GC:G	acceptor_gain	0.9900
15:40573526:GCTGG:G	acceptor_gain	0.9900

AlphaMissense

3525 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:40571727:C:G	H244D	0.999
15:40571818:A:T	D274V	0.999
15:40569798:A:T	K154I	0.998
15:40569845:T:C	F170L	0.998
15:40569847:C:A	F170L	0.998
15:40569847:C:G	F170L	0.998
15:40571650:T:A	V218D	0.998
15:40571725:T:A	V243D	0.998
15:40571729:C:A	H244Q	0.998
15:40571729:C:G	H244Q	0.998
15:40571818:A:C	D274A	0.998
15:40573539:T:C	Y306H	0.998
15:40574232:T:A	W537R	0.998
15:40574232:T:C	W537R	0.998
15:40569782:T:C	F149L	0.997
15:40569784:C:A	F149L	0.997
15:40569784:C:G	F149L	0.997
15:40569796:C:G	C153W	0.997
15:40569799:A:C	K154N	0.997
15:40569799:A:T	K154N	0.997
15:40569806:T:A	W157R	0.997
15:40569806:T:C	W157R	0.997
15:40569808:G:C	W157C	0.997
15:40569808:G:T	W157C	0.997
15:40571832:G:T	G279W	0.997
15:40571833:G:A	G279E	0.997
15:40573750:T:C	L376P	0.997
15:40571631:C:G	H212D	0.996
15:40571642:G:C	E215D	0.996
15:40571642:G:T	E215D	0.996

dbSNP variants (sampled 300 via entrez): RS1001100168 (15:40572658 G>A), RS1001541998 (15:40571073 A>C,G), RS1001811025 (15:40568318 G>A,T), RS1001883335 (15:40568568 G>C,T), RS1002151269 (15:40574625 G>A,T), RS1002936636 (15:40569883 C>G,T), RS1003217942 (15:40572313 A>G), RS1003438980 (15:40572500 A>C), RS1004928564 (15:40572341 T>C), RS1005061838 (15:40572896 G>C), RS1005375484 (15:40570150 A>C,T), RS1005779159 (15:40568150 G>A), RS1005892711 (15:40573562 G>A,T), RS1006330887 (15:40574474 G>A,T), RS1006376282 (15:40568829 G>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

4 associations (top):

Study	Trait	p-value
GCST010002_167	Refractive error	3.000000e-11
GCST010725_23	Malaria	2.000000e-06
GCST010725_38	Malaria	3.000000e-06
GCST010725_80	Malaria	7.000000e-06

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
sodium arsenite	affects cotreatment, decreases expression	3
Cadmium Chloride	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Rosiglitazone	affects cotreatment, decreases expression	1
Pioglitazone	affects cotreatment, decreases expression	1
Troglitazone	decreases expression, decreases reaction	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Potassium Dichromate	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1
tert-Butylhydroperoxide	decreases reaction, affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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