PUS1 (pseudouridine synthase 1)

Gene

• Entrez ID: 80324
• Gene name: Pseudouridine synthase 1
• Gene symbol: PUS1
• Synonyms (NCBI Gene): MLASA1
• Chromosome: 12
• Chromosome location: 12q24.33
• Summary: This gene encodes a pseudouridine synthase that converts uridine to pseudouridine once it has been incorporated into an RNA molecule. The encoded enzyme may play an essential role in tRNA function and in stabilizing the secondary and tertiary structure of

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894371	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs104894372	G>T	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained, genic downstream transcript variant
rs149378338	C>A,T	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs372753711	G>A	Likely-pathogenic	Missense variant, genic downstream transcript variant, non coding transcript variant, coding sequence variant
rs779193823	C>G,T	Pathogenic	Synonymous variant, non coding transcript variant, stop gained, genic downstream transcript variant, coding sequence variant
rs779651314	C>A	Likely-pathogenic	Stop gained, genic downstream transcript variant, non coding transcript variant, coding sequence variant
rs863224176	A>C	Likely-pathogenic	Genic downstream transcript variant, missense variant, non coding transcript variant, coding sequence variant
rs869025309	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, missense variant
rs1555268564	->G	Likely-pathogenic	Frameshift variant, genic downstream transcript variant, non coding transcript variant, coding sequence variant
rs1566148136	C>-	Likely-pathogenic	Genic downstream transcript variant, frameshift variant, coding sequence variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022192	hsa-miR-124-3p	Microarray	18668037
MIRT027453	hsa-miR-98-5p	Microarray	19088304
MIRT032213	hsa-let-7b-5p	Proteomics	18668040
MIRT041439	hsa-miR-193b-3p	CLASH	23622248
MIRT1277969	hsa-miR-1184	CLIP-seq
MIRT1277970	hsa-miR-1200	CLIP-seq
MIRT1277971	hsa-miR-3160-3p	CLIP-seq
MIRT1277972	hsa-miR-335	CLIP-seq
MIRT1277973	hsa-miR-3622b-5p	CLIP-seq
MIRT1277974	hsa-miR-4304	CLIP-seq
MIRT1277975	hsa-miR-4324	CLIP-seq
MIRT1277976	hsa-miR-4663	CLIP-seq
MIRT1277977	hsa-miR-4666-5p	CLIP-seq
MIRT1277978	hsa-miR-4668-5p	CLIP-seq
MIRT1277979	hsa-miR-4696	CLIP-seq
MIRT1277980	hsa-miR-4728-3p	CLIP-seq
MIRT1277981	hsa-miR-4743	CLIP-seq
MIRT1277982	hsa-miR-4747-5p	CLIP-seq
MIRT1277983	hsa-miR-493	CLIP-seq
MIRT1277984	hsa-miR-544b	CLIP-seq
MIRT1277985	hsa-miR-570	CLIP-seq
MIRT1277986	hsa-miR-604	CLIP-seq
MIRT1277987	hsa-miR-647	CLIP-seq
MIRT1277988	hsa-miR-34b	CLIP-seq
MIRT1277976	hsa-miR-4663	CLIP-seq
MIRT1277977	hsa-miR-4666-5p	CLIP-seq
MIRT1277980	hsa-miR-4728-3p	CLIP-seq
MIRT1277971	hsa-miR-3160-3p	CLIP-seq
MIRT1277982	hsa-miR-4747-5p	CLIP-seq
MIRT1277983	hsa-miR-493	CLIP-seq
MIRT1277985	hsa-miR-570	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IDA	23707380
GO:0001522	Process	Pseudouridine synthesis	IEA
GO:0002153	Function	Steroid receptor RNA activator RNA binding	IDA	24722331
GO:0003682	Function	Chromatin binding	IEA
GO:0003713	Function	Transcription coactivator activity	IEA
GO:0003723	Function	RNA binding	HDA	22658674, 22681889
GO:0003723	Function	RNA binding	IEA
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	15772074
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005667	Component	Transcription regulator complex	IEA
GO:0005730	Component	Nucleolus	IEA
GO:0005737	Component	Cytoplasm	IDA	15772074
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IDA	15772074, 28082677
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006397	Process	MRNA processing	IEA
GO:0008033	Process	TRNA processing	IEA
GO:0008380	Process	RNA splicing	IEA
GO:0009451	Process	RNA modification	IEA
GO:0009982	Function	Pseudouridine synthase activity	EXP	15772074, 22102571
GO:0009982	Function	Pseudouridine synthase activity	IBA
GO:0009982	Function	Pseudouridine synthase activity	IDA	31477916, 35051350
GO:0009982	Function	Pseudouridine synthase activity	IEA
GO:0009982	Function	Pseudouridine synthase activity	IMP	15772074, 24722331
GO:0016853	Function	Isomerase activity	IEA
GO:0031119	Process	TRNA pseudouridine synthesis	IBA
GO:0031119	Process	TRNA pseudouridine synthesis	IEA
GO:0031119	Process	TRNA pseudouridine synthesis	IEA
GO:0031119	Process	TRNA pseudouridine synthesis	IMP	15772074
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0070902	Process	Mitochondrial tRNA pseudouridine synthesis	TAS
GO:0106029	Function	TRNA pseudouridine synthase activity	IEA
GO:0160147	Function	TRNA pseudouridine(38-40) synthase activity	IEA
GO:1990481	Process	MRNA pseudouridine synthesis	IBA
GO:1990481	Process	MRNA pseudouridine synthesis	IDA	31477916, 35051350

Other IDs

• MIM: 608109
• HGNC: 15508
• e!Ensembl: ENSG00000177192

Protein

• UniProt ID: Q9Y606
• Protein name: Pseudouridylate synthase 1 homolog (EC 5.4.99.-) (tRNA pseudouridine synthase 1) (EC 5.4.99.12) (tRNA pseudouridine(38-40) synthase) (tRNA pseudouridylate synthase I) (tRNA-uridine isomerase I)
• Protein function: Pseudouridylate synthase that catalyzes pseudouridylation of tRNAs and mRNAs (PubMed:15772074, PubMed:24722331). Acts on positions 27/28 in the anticodon stem and also positions 34 and 36 in the anticodon of an intron containing tRNA (PubMed:247
• PDB: 4IQM, 4ITS, 4J37, 4NZ6, 4NZ7
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01416	PseudoU_synth_1	235 → 341	tRNA pseudouridine synthase	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed (PubMed:15108122). High levels of expression found in brain and skeletal muscle (PubMed:15108122). {ECO:0000269|PubMed:15108122}.
• Sequence:

  MGLQLRALLGAFGRWTLRLGPRPSCSPRMAGNAEPPPAGAACPQDRRSCSGRAGGDRVWE
  DGEHPAKKLKSGGDEERREKPPKRKIVLLMAYSGKGYHGMQRNVGSSQFKTIEDDLVSAL
  VRSGCIPENHGEDMRKMSFQRCARTDKGVSAAGQVVSLKVWLIDDILEKINSHLPSHIRI
  LGLKRVTGGFNSKNRCDARTYCYLLPTFAFAHKDRDVQDETYRLSAETLQQVNRLLACYK
  GTHNFHNFTSQKGPQDPSACRYILEMYCEEPFVREGLEFAVIRVKGQSFMMHQIRKMVGL
  VVAIVKGYAPESVLERSWGTEKVDVPKAPGLGLVLERVHFEKYNQRFGNDGLHEPLDWAQ
  EEGKVAAFKEEHIYPTIIGTERDERSMAQWLSTLPIHNFSATALTAGGTGAKVPSPLEGS
  EGDGDTD

• Sequence length: 427

Pathways

Reactome:

tRNA modification in the mitochondrion

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Myopathy, lactic acidosis, and sideroblastic anemia	Likely pathogenic; Pathogenic	rs1555268564, rs1048018914	RCV001829384 RCV005606789	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Myopathy, lactic acidosis, and sideroblastic anemia 1	Likely pathogenic; Pathogenic	rs754855677, rs895175332, rs104894371, rs104894372, rs1323139544, rs2540870188, rs2540862808, rs2541388871, rs1309276486, rs869025309, rs2540870135, rs2540872758, rs2540873492, rs751632633, rs2541389252, rs2541388990, rs2540870303, rs2540873585, rs2540873523, rs2541388135, rs2540874019, rs2540870199, rs779651314, rs1555268564, rs1566148136, rs779193823	RCV004571708 RCV002283570 RCV000002645 RCV000002646 RCV002470133 RCV003459727 RCV003464621 RCV003464624 RCV003459711 RCV000207447 RCV003463403 RCV003463404 RCV003471753 RCV003463405 RCV003463406 RCV003463407 RCV003471754 RCV003463408 RCV003471755 RCV003471756 RCV005006338 RCV004573417 RCV003990582 RCV000454345 RCV004568212 RCV000714784 RCV000853196	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
PUS1-related disorder	Likely pathogenic; Pathogenic	rs895175332, rs2541388135, rs2540874019	RCV003401940 RCV003902236 RCV003899398	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	Pathogenic	rs2540873599	RCV006444135	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Inborn mitochondrial myopathy	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial disease	Uncertain significance	ClinVar ClinGen, Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL MYOPATHY AND SIDEROBLASTIC ANEMIA	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOPATHY WITH LACTIC ACIDOSIS AND SIDEROBLASTIC ANEMIA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POSTERIOR CORTICAL ATROPHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sideroblastic anemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STOMACH NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Erythroid hyperplasia	Erythroid hyperplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Generalized limb muscle atrophy	Limb Muscle Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hereditary Diffuse Gastric Cancer	Gastric Cancer	CTD_human_DG	21364753		★☆☆☆☆ Found in Text Mining only
Hypochromic anemia	Hypochromic anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	21686963		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Iron-Refractory Iron Deficiency Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	30664217		★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	30664217		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	CTD_human_DG	21364753		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	15772074, 25227147	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	25037980		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Myopathies	Mitochondrial myopathy	LHGDN	15108122		★☆☆☆☆ Found in Text Mining only
Mitochondrial Myopathies	Mitochondrial myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
MITOCHONDRIAL MYOPATHY AND SIDEROBLASTIC ANEMIA	Mitochondrial Myopathy And Sideroblastic Anemia	BEFREE	17056637, 20598274, 23918765, 25037980		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL MYOPATHY AND SIDEROBLASTIC ANEMIA	Mitochondrial Myopathy And Sideroblastic Anemia	GENOMICS_ENGLAND_DG	21686963		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL MYOPATHY AND SIDEROBLASTIC ANEMIA	Mitochondrial Myopathy And Sideroblastic Anemia	ORPHANET_DG	21686963		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial myopathy and sideroblastic anemia	Mitochondrial Myopathy And Sideroblastic Anemia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL MYOPATHY AND SIDEROBLASTIC ANEMIA	Mitochondrial Myopathy And Sideroblastic Anemia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myopathy	Myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myopathy with lactic acidosis and sideroblastic anemia	Mitochondrial myopathy with sideroblastic anemia	Pubtator	15108122, 15772074, 20598274, 25037980	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOPATHY, LACTIC ACIDOSIS, AND SIDEROBLASTIC ANEMIA 1	Myopathy, lactic acidosis, and sideroblastic anemia	UNIPROT_DG	15108122, 16959974, 19731322		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MYOPATHY, LACTIC ACIDOSIS, AND SIDEROBLASTIC ANEMIA 1	Myopathy, lactic acidosis, and sideroblastic anemia	GENOMICS_ENGLAND_DG	15108122, 21686963, 25227147, 26556812, 27604308		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MYOPATHY, LACTIC ACIDOSIS, AND SIDEROBLASTIC ANEMIA 1	Myopathy, lactic acidosis, and sideroblastic anemia	BEFREE	30588737		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MYOPATHY, LACTIC ACIDOSIS, AND SIDEROBLASTIC ANEMIA 1	Myopathy, lactic acidosis, and sideroblastic anemia	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Osteoarthritis	Osteoarthritis	Pubtator	37006267	Associate	★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sideroblastic anemia	Sideroblastic Anemia	LHGDN	15108122		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sideroblastic anemia	Sideroblastic Anemia	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Stomach Neoplasms	Stomach Neoplasms	CTD_human_DG	21364753		★★☆☆☆ Found in Text Mining + Unknown/Other Associations