PUS10

protein-coding

pseudouridine synthase 10, the group of Pseudouridine synthases

Gene summary

Pseudouridination, the isomerization of uridine to pseudouridine, is the most common posttranscriptional nucleotide modification found in RNA and is essential for biologic functions such as spliceosome biogenesis. Pseudouridylate synthases, such as PUS10, catalyze pseudouridination of structural RNAs, including transfer, ribosomal, and splicing RNAs. These enzymes also act as RNA chaperones, facilitating the correct folding and assembly of tRNAs (McCleverty et al., 2007 [PubMed 17900615]).[supplied by OMIM, May 2009]

Previous symbols:

CCDC139

MANE transcript

NM_144709.4

Inheritance

—

ClinVar variants

U:69B:3

Top phenotype

Peroxisome biogenesis disorder 11A (Zellweger)

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr2:60,939,610-61,018,259

External References & Databases

Ensembl (ENSG00000162927)

Transcript & Mutation Effects

hg38 • Region Span ~78.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PUS10 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 77

Peroxisome biogenesis disorder 11A (Zellweger)Total: 67

not providedTotal: 15

PEX13-related disorderTotal: 10

Inborn genetic diseasesTotal: 10

Peroxisome biogenesis disorder 11BTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144709.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			66 clinvar	2 clinvar		68
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	69	3	0	72

Highest pathogenic variant AF is 0.000029669074

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 79 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144709.4	RefSeq	NP_653310.2	17	MANE Select
ENST00000316752.11	Ensembl	ENSP00000326003.6	17	MANE Select
NM_001322123.1	RefSeq	NP_001309052.1	17	Standard
NM_001322124.1	RefSeq	NP_001309053.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

tRNA pseudouridine synthesis

Molecular Function

RNA binding
pseudouridine synthase activity
tRNA pseudouridine synthase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316752
Coding exons: 17
Length: 78038
Individuals with no LoFs: 115833
Homozygous LoFs: 0
Heterozygous LoFs: 9915
Defined: 125748
p: 0.0402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0423	264	266	0.993	0.0000129	3489
Missense (PolyPhen)		73	84.142	0.86758		1055
Synonymous	-0.735	105	95.9	1.10	0.00000484	959
Loss of Function	1.37	25	33.6	0.745	0.00000175	408

Population LoF Frequency

Population	CAF	p-value	Status
African	0.040	0.035	notable
Latino/Admixed American	0.023	0.022	notable
Ashkenazi Jewish	0.015	0.014	notable
East Asian	0.054	0.050	notable
Finnish	0.053	0.049	notable
European (Non-Finnish)	0.058	0.055	notable
South Asian	0.012	0.011	notable
Other	0.029	0.027	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Pseudouridylate synthases catalyze pseudouridination of structural RNAs, including transfer, ribosomal, and splicing RNAs. PUS10 catalyzes the formation of the universal psi55 in the GC loop of transfer RNAs (Probable). Modulator of TRAIL-induced cell death via activation of procaspase 8 and BID cleavage. Required for the progression of the apoptotic signal through intrinsic mitochondrial cell death. {ECO:0000269|PubMed:14527409, ECO:0000269|PubMed:19712588, ECO:0000305}.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.451
RVIS EVS: -0.49
RVIS percentile EVS: 22.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.402

Gene Damage Prediction

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