PUSL1

Summary

PUSL1 (pseudouridine synthase like 1, HGNC:26914) is a protein-coding gene on chromosome 1p36.33, encoding tRNA pseudouridine synthase-like 1 (Q8N0Z8).

Predicted to enable pseudouridine synthase activity. Predicted to be involved in tRNA pseudouridine synthesis. Located in mitochondrion.

Source: NCBI Gene 126789 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 76 total — 1 pathogenic
• MANE Select transcript: NM_153339

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26914
Approved symbol	PUSL1
Name	pseudouridine synthase like 1
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90811
Ensembl gene	ENSG00000169972
Ensembl biotype	protein_coding
Entrez	126789

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000379031, ENST00000463758, ENST00000467712, ENST00000470520, ENST00000493657, ENST00000706601, ENST00000706602, ENST00000892132, ENST00000892133

RefSeq mRNA: 2 — MANE Select: NM_153339 NM_001346116, NM_153339

CCDS: CCDS20

Canonical transcript exons

ENST00000379031 — 8 exons

Exon	Start	End
ENSE00001225918	1310909	1311071
ENSE00001225948	1308915	1308972
ENSE00001853015	1308597	1308720
ENSE00001893383	1311330	1311677
ENSE00003513130	1309681	1309851
ENSE00003604149	1309086	1309273
ENSE00003668395	1310634	1310688
ENSE00003688171	1309454	1309603

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 89.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.6238 / max 131.3761, expressed in 1764 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81	14.9036	1759
82	0.4941	260
83	0.2261	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	89.55	gold quality
buccal mucosa cell	CL:0002336	87.83	gold quality
mucosa of transverse colon	UBERON:0004991	87.07	gold quality
esophagus mucosa	UBERON:0002469	86.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.52	gold quality
skin of leg	UBERON:0001511	85.28	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.24	gold quality
skin of abdomen	UBERON:0001416	85.05	gold quality
granulocyte	CL:0000094	84.79	gold quality
apex of heart	UBERON:0002098	84.50	gold quality
adenohypophysis	UBERON:0002196	84.16	gold quality
right adrenal gland	UBERON:0001233	83.93	gold quality
ectocervix	UBERON:0012249	83.87	gold quality
right adrenal gland cortex	UBERON:0035827	83.81	gold quality
pituitary gland	UBERON:0000007	83.32	gold quality
esophagus	UBERON:0001043	83.28	gold quality
left adrenal gland cortex	UBERON:0035825	83.28	gold quality
zone of skin	UBERON:0000014	83.12	gold quality
minor salivary gland	UBERON:0001830	83.10	gold quality
left adrenal gland	UBERON:0001234	82.97	gold quality
body of stomach	UBERON:0001161	82.87	gold quality
left uterine tube	UBERON:0001303	82.25	gold quality
mouth mucosa	UBERON:0003729	82.14	gold quality
saliva-secreting gland	UBERON:0001044	81.94	gold quality
endocervix	UBERON:0000458	81.89	gold quality
adrenal cortex	UBERON:0001235	81.89	gold quality
body of uterus	UBERON:0009853	81.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.41	gold quality
right uterine tube	UBERON:0001302	81.26	gold quality
body of pancreas	UBERON:0001150	81.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting PUSL1, 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-6515-3P	99.82	68.19	1933
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-431-5P	96.16	66.50	652
HSA-MIR-5002-3P	95.75	67.04	542
HSA-MIR-2861	95.24	65.47	1056

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pusl1	ENSDARG00000074565
mus_musculus	Pusl1	ENSMUSG00000051557
rattus_norvegicus	Pusl1	ENSRNOG00000022354
drosophila_melanogaster	CG34140	FBGN0083976
caenorhabditis_elegans		WBGENE00022250

Paralogs (2): PUS3 (ENSG00000110060), PUS1 (ENSG00000177192)

Protein

Protein identifiers

tRNA pseudouridine synthase-like 1 — Q8N0Z8 (reviewed: Q8N0Z8)

Alternative names: tRNA pseudouridylate synthase-like 1, tRNA-uridine isomerase-like 1

All UniProt accessions (2): Q8N0Z8, J3KTG4

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the tRNA pseudouridine synthase TruA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N0Z8-1	1	yes
Q8N0Z8-2	2

RefSeq proteins (2): NP_001333045, NP_699170* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001406	PsdUridine_synth_TruA	Family
IPR020094	TruA/RsuA/RluB/E/F_N	Homologous_superfamily
IPR020095	PsdUridine_synth_TruA_C	Homologous_superfamily
IPR020097	PsdUridine_synth_TruA_a/b_dom	Domain
IPR020103	PsdUridine_synth_cat_dom_sf	Homologous_superfamily

Pfam: PF01416

Catalyzed reactions (Rhea), 1 shown:

• a uridine in tRNA = a pseudouridine in tRNA (RHEA:54572)

UniProt features (7 total): sequence variant 2, chain 1, active site 1, binding site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N0Z8-F1	91.59	0.84

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): 66 (nucleophile)

Ligand- & substrate-binding residues (1): 130

Post-translational modifications (1): 84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_PSEUDOURIDINE_SYNTHESIS, GOBP_RNA_MODIFICATION, LIAO_METASTASIS, GOBP_TRNA_PROCESSING, GOBP_TRNA_MODIFICATION, GOMF_PSEUDOURIDINE_SYNTHASE_ACTIVITY, GOMF_INTRAMOLECULAR_TRANSFERASE_ACTIVITY, GOMF_ISOMERASE_ACTIVITY, chr1p36, MARTENS_TRETINOIN_RESPONSE_DN, LU_EZH2_TARGETS_UP, GOBP_TRNA_PSEUDOURIDINE_SYNTHESIS, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_A_TRNA

GO Biological Process (4): tRNA pseudouridine synthesis (GO:0031119), pseudouridine synthesis (GO:0001522), tRNA processing (GO:0008033), RNA modification (GO:0009451)

GO Molecular Function (5): RNA binding (GO:0003723), pseudouridine synthase activity (GO:0009982), tRNA pseudouridine synthase activity (GO:0106029), isomerase activity (GO:0016853), tRNA pseudouridine(38-40) synthase activity (GO:0160147)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pseudouridine synthesis	1
tRNA modification	1
RNA modification	1
RNA processing	1
tRNA metabolic process	1
RNA metabolic process	1
macromolecule modification	1
nucleic acid binding	1
intramolecular transferase activity	1
pseudouridine synthase activity	1
catalytic activity, acting on a tRNA	1
catalytic activity	1
tRNA pseudouridine synthase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PUSL1	RPUSD4	Q96CM3	727
PUSL1	RPUSD3	Q6P087	727
PUSL1	TRUB2	O95900	714
PUSL1	PUS7L	Q9H0K6	709
PUSL1	TRUB1	Q8WWH5	648
PUSL1	PUS7	Q96PZ0	609
PUSL1	RPUSD1	Q9UJJ7	608
PUSL1	PUS10	Q3MIT2	605
PUSL1	ACAP3	Q96P50	595
PUSL1	RPUSD2	Q8IZ73	584
PUSL1	TMEM244	Q5VVB8	559
PUSL1	TMEM141	Q96I45	540
PUSL1	WDR33	Q9C0J8	511
PUSL1	TRPT1	Q86TN4	507
PUSL1	TPST1	O60507	500

IntAct

81 interactions, top by confidence:

A	B	Type	Score
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
KIF24	CCP110	psi-mi:“MI:0914”(association)	0.810
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
TRIP13	INTS11	psi-mi:“MI:0914”(association)	0.550
KLHL40	CBX4	psi-mi:“MI:0914”(association)	0.530
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
	PLOD2	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
DISC1	AP4M1	psi-mi:“MI:0914”(association)	0.530
PSME1	POLR3A	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
IMPDH2	IMPDH1	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
PYCR3	RPL23	psi-mi:“MI:0914”(association)	0.530
SRSF3	CASC3	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
FOXF1	CPS1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350
IMPDH1	LCMT2	psi-mi:“MI:0914”(association)	0.350
ISOC2	MPP2	psi-mi:“MI:0914”(association)	0.350
TRIP13	METTL8	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS)

ESM2 similar proteins: A2ADA5, A4PCD4, A6H611, D3ZDM7, F6PHZ6, O75344, P04053, P09838, P17256, P36195, P47823, P55345, Q01992, Q03426, Q08602, Q0V8R7, Q13144, Q1L8I0, Q3MIT2, Q4KM92, Q4QQT0, Q5CZL1, Q5E9Z1, Q5I0L3, Q5M7T9, Q5M934, Q5RFE6, Q5XGM5, Q64350, Q6GQ53, Q7L3T8, Q80W22, Q86YJ6, Q8BYL4, Q8C0D0, Q8CHW4, Q8N0Z8, Q8WWH5, Q91XW8, Q92089

Diamond homologs: A1AZF2, A1TLH0, A1VF73, A1WAT5, A2ADA5, A2SHS6, A3PLW1, A4G4G0, A4IJL9, A4J151, A4VT40, A4VZC6, A4WPU4, A5VLH4, A6U5I6, A7HPQ3, A7IKI9, A8F079, A8GQ80, A8GU17, A8GUM4, A8LNZ7, A9BNH5, A9IRL0, A9W377, B0BVL0, B0K5S6, B0KCN3, B0T1S6, B0UP40, B1I1B5, B1M6N9, B1YH83, B1ZGA6, B2G8U7, B2GDT8, B2IEW0, B3E0A0, B5E6N8, B6JJP6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	58
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
152695	GRCh38/hg38 1p36.33-36.32(chr1:821713-2976123)x1	Pathogenic

SpliceAI

1452 predictions. Top by Δscore:

Variant	Effect	Δscore
1:1308700:G:GG	donor_gain	1.0000
1:1308721:G:GG	donor_gain	1.0000
1:1309081:TGCAG:T	acceptor_loss	1.0000
1:1309082:GCAGG:G	acceptor_loss	1.0000
1:1309083:CA:C	acceptor_loss	1.0000
1:1309085:G:GT	acceptor_loss	1.0000
1:1309269:ATCAG:A	donor_loss	1.0000
1:1309270:TCAGG:T	donor_loss	1.0000
1:1309271:CAGGT:C	donor_loss	1.0000
1:1309272:AGGTG:A	donor_loss	1.0000
1:1309273:GGT:G	donor_loss	1.0000
1:1309274:GTGAG:G	donor_loss	1.0000
1:1309275:T:G	donor_loss	1.0000
1:1309599:GCAGA:G	donor_gain	1.0000
1:1309602:GA:G	donor_gain	1.0000
1:1309603:AGTG:A	donor_loss	1.0000
1:1309604:G:GG	donor_gain	1.0000
1:1309847:AGCAG:A	donor_loss	1.0000
1:1309849:CAGG:C	donor_loss	1.0000
1:1309850:AG:A	donor_loss	1.0000
1:1309851:GG:G	donor_loss	1.0000
1:1309852:G:GC	donor_loss	1.0000
1:1309853:T:A	donor_loss	1.0000
1:1310903:TCACA:T	acceptor_loss	1.0000
1:1310904:CACAG:C	acceptor_loss	1.0000
1:1310905:ACAG:A	acceptor_loss	1.0000
1:1310906:CAGGT:C	acceptor_loss	1.0000
1:1310907:AGG:A	acceptor_loss	1.0000
1:1311070:CGGTA:C	donor_loss	1.0000
1:1311072:G:GC	donor_loss	1.0000

AlphaMissense

1934 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:1310674:T:C	F229L	0.996
1:1310676:C:A	F229L	0.996
1:1310676:C:G	F229L	0.996
1:1309147:A:T	D66V	0.993
1:1309137:A:C	S63R	0.992
1:1309139:C:A	S63R	0.992
1:1309139:C:G	S63R	0.992
1:1310665:A:C	S226R	0.992
1:1310667:C:A	S226R	0.992
1:1310667:C:G	S226R	0.992
1:1309148:C:A	D66E	0.991
1:1309148:C:G	D66E	0.991
1:1309177:C:A	A76E	0.990
1:1309485:T:C	F119L	0.990
1:1309487:C:A	F119L	0.990
1:1309487:C:G	F119L	0.990
1:1309739:T:C	F178L	0.990
1:1309741:C:A	F178L	0.990
1:1309741:C:G	F178L	0.990
1:1309172:C:A	N74K	0.987
1:1309172:C:G	N74K	0.987
1:1309270:T:A	I107N	0.987
1:1309456:T:A	V109D	0.987
1:1308701:T:C	Y20H	0.986
1:1308956:T:A	V40D	0.985
1:1309492:C:A	A121D	0.985
1:1309748:T:C	F181L	0.985
1:1309750:C:A	F181L	0.985
1:1309750:C:G	F181L	0.985
1:1308716:T:C	F25L	0.984

dbSNP variants (sampled 300 via entrez): RS1000013557 (1:1307957 G>C,T), RS1000473668 (1:1309380 G>A,C), RS1000778377 (1:1308812 C>G,T), RS1001132193 (1:1307695 A>C,G), RS1001242875 (1:1311218 C>A,G,T), RS1002443569 (1:1307305 T>G), RS1002476475 (1:1307166 T>C), RS1003161341 (1:1312034 A>G), RS1003249853 (1:1309884 C>G,T), RS1003322835 (1:1310452 T>C), RS1003576339 (1:1309070 C>G,T), RS1004482448 (1:1307512 G>A,T), RS1004845635 (1:1306711 C>T), RS1005270034 (1:1309970 G>A), RS1005493668 (1:1310328 C>A,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

2 associations (top):

Study	Trait	p-value
GCST004131_103	Inflammatory bowel disease	2.000000e-07
GCST004133_40	Ulcerative colitis	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
jinfukang	increases expression	1
Sunitinib	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Phenobarbital	affects expression	1
Rotenone	increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TH75	HAP1 PUSL1 (-) 1	Cancer cell line	Male
CVCL_XS05	HAP1 PUSL1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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