PUS1

pseudouridine synthase 1, the group of Pseudouridine synthases

Basic information

Region (hg38): 12:131929200-131945896

Links

ENSG00000177192 ∙ NCBI:80324 ∙ OMIM:608109 ∙ HGNC:15508 ∙ Uniprot:Q9Y606 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopathy, lactic acidosis, and sideroblastic anemia 1 (Definitive), mode of inheritance: AR
• myopathy, lactic acidosis, and sideroblastic anemia 1 (Moderate), mode of inheritance: AR
• myopathy, lactic acidosis, and sideroblastic anemia (Supportive), mode of inheritance: AR
• myopathy, lactic acidosis, and sideroblastic anemia 1 (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, lactic acidosis, and sideroblastic anemia 1	AR	Hematologic	Severe, non-B6 responsive anemia has reportedly required transfusions	Endocrine; Hematologic; Musculoskeletal; Neurologic	7726239; 14981724; 15108122; 15103716; 17056637; 19731322; 25227147

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PUS1 gene.

• not provided (25 variants)
• Myopathy, lactic acidosis, and sideroblastic anemia 1 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PUS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				260	3	263
missense		2	108	8		118
nonsense	8	6				14
start loss			2			2
frameshift	18	9				27
inframe indel						0
splice donor/acceptor (+/-2bp)		9				9
splice region			2	27	1	30
non coding			14	59	12	85
Total	26	26	124	327	15

Highest pathogenic variant AF is 0.00000657

Variants in PUS1

This is a list of pathogenic ClinVar variants found in the PUS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-131929266-G-C		Myopathy, lactic acidosis, and sideroblastic anemia 1	Uncertain significance (Jan 13, 2018)
12-131929270-C-T		Myopathy, lactic acidosis, and sideroblastic anemia 1	Uncertain significance (Jan 12, 2018)
12-131929299-C-T		Myopathy, lactic acidosis, and sideroblastic anemia 1	Uncertain significance (Jan 13, 2018)
12-131929436-G-C		Myopathy, lactic acidosis, and sideroblastic anemia 1	Uncertain significance (Jan 13, 2018)
12-131929457-G-C		Myopathy, lactic acidosis, and sideroblastic anemia 1	Uncertain significance (Jan 13, 2018)
12-131929477-G-A		Myopathy, lactic acidosis, and sideroblastic anemia 1	Uncertain significance (Jan 12, 2018)
12-131929479-G-C		Myopathy, lactic acidosis, and sideroblastic anemia 1	Uncertain significance (Jan 13, 2018)
12-131929541-C-T		Myopathy, lactic acidosis, and sideroblastic anemia 1	Benign (Jun 14, 2018)
12-131929572-G-A		Myopathy, lactic acidosis, and sideroblastic anemia 1	Uncertain significance (Jan 13, 2018)
12-131929643-G-A		Myopathy, lactic acidosis, and sideroblastic anemia 1	Uncertain significance (Jan 13, 2018)
12-131929674-G-T		not specified	Likely benign (Jan 31, 2018)
12-131929677-A-G		not specified	Likely benign (Sep 06, 2017)
12-131929723-A-G			Uncertain significance (Sep 01, 2022)
12-131929724-T-G		PUS1-related disorder	Uncertain significance (Jan 10, 2024)
12-131929728-C-A			Likely benign (Apr 06, 2023)
12-131929728-C-T			Likely benign (Sep 04, 2023)
12-131929730-T-A		Inborn genetic diseases	Uncertain significance (Apr 23, 2024)
12-131929731-C-G			Likely benign (Mar 24, 2023)
12-131929732-C-T			Pathogenic (Nov 19, 2021)
12-131929734-G-A			Likely benign (Dec 10, 2022)
12-131929739-G-A			Uncertain significance (Apr 04, 2022)
12-131929740-C-T			Likely benign (Nov 06, 2023)
12-131929742-C-T			Uncertain significance (Dec 24, 2021)
12-131929743-G-C			Likely benign (Jul 26, 2019)
12-131929743-G-T			Likely benign (Jul 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PUS1	protein_coding	protein_coding	ENST00000376649	6	14662

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00167	0.974	125729	0	12	125741	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.291	250	263	0.949	0.0000171	2758
Missense in Polyphen		85	106.14	0.80084		1133
Synonymous	-0.154	123	121	1.02	0.00000867	861
Loss of Function	1.98	7	15.4	0.455	6.57e-7	193

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000447	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts specific uridines to PSI in a number of tRNA substrates. Acts on positions 27/28 in the anticodon stem and also positions 34 and 36 in the anticodon of an intron containing tRNA. Involved in regulation of nuclear receptor activity through pseudouridylation of SRA1 RNA. {ECO:0000269|PubMed:24722331}.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;tRNA modification in the mitochondrion;Metabolism of RNA;Pyrimidine metabolism (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.684
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.58

Haploinsufficiency Scores

• pHI: 0.487
• hipred: Y
• hipred_score: 0.565
• ghis: 0.599

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.940

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pus1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: tRNA pseudouridine synthesis;mitochondrial tRNA pseudouridine synthesis;mRNA pseudouridine synthesis
• Cellular component: nucleus;mitochondrion;mitochondrial matrix
• Molecular function: tRNA binding;steroid receptor RNA activator RNA binding;RNA binding;pseudouridine synthase activity;tRNA pseudouridine synthase activity