PUS7

pseudouridine synthase 7, the group of Pseudouridine synthases

Basic information

Region (hg38): 7:105439661-105522271

Links

ENSG00000091127 ∙ NCBI:54517 ∙ OMIM:616261 ∙ HGNC:26033 ∙ Uniprot:Q96PZ0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with abnormal behavior, microcephaly, and short stature (Moderate), mode of inheritance: AR
• syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual developmental disorder with abnormal behavior, microcephaly, and short stature (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic	30526862; 30778726

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PUS7 gene.

• Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature (1 variants)
• not provided (1 variants)
• Inborn genetic diseases (1 variants)
• See cases (1 variants)
• Pervasive developmental disorder;Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PUS7 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				9	2	11
missense		1	40	3	1	45
nonsense	1	1				2
start loss						0
frameshift	4	4				8
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			1	2	3	6
non coding					4	4
Total	5	8	40	12	7

Highest pathogenic variant AF is 0.00000657

Variants in PUS7

This is a list of pathogenic ClinVar variants found in the PUS7 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-105457785-A-G		PUS7-related disorder	Benign (Dec 31, 2019)
7-105457792-A-G		Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature	Uncertain significance (Apr 04, 2024)
7-105457794-C-T		Inborn genetic diseases	Uncertain significance (May 05, 2022)
7-105457818-G-A		Inborn genetic diseases	Uncertain significance (May 31, 2023)
7-105457841-C-T			Uncertain significance (Jun 25, 2021)
7-105459242-TC-T		See cases	Pathogenic (Apr 26, 2021)
7-105459248-G-A		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
7-105462727-G-T		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
7-105462747-T-C			Uncertain significance (Oct 12, 2023)
7-105465343-C-T			Uncertain significance (Jan 30, 2023)
7-105468355-C-A		Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature	Pathogenic/Likely pathogenic (Mar 17, 2024)
7-105468381-T-C		Inborn genetic diseases	Uncertain significance (Mar 20, 2023)
7-105468395-G-T		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
7-105468442-T-C		Inborn genetic diseases	Uncertain significance (May 30, 2024)
7-105468457-T-C		Inborn genetic diseases	Uncertain significance (Jun 10, 2024)
7-105470697-T-C		PUS7-related disorder	Benign (Dec 20, 2018)
7-105470699-CAG-C		Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature	Likely pathogenic (-)
7-105470738-G-A		Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature	Pathogenic (Dec 06, 2018)
7-105470770-G-A		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
7-105470772-T-C		PUS7-related disorder	Benign (Jul 31, 2019)
7-105470823-G-C		Inborn genetic diseases	Uncertain significance (Jul 15, 2021)
7-105472170-G-A		Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
7-105472173-C-T		Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature	Likely pathogenic (Oct 28, 2022)
7-105481067-G-A		Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature • Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 21, 2022)
7-105481072-G-T		PUS7-related disorder	Likely benign (Nov 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PUS7	protein_coding	protein_coding	ENST00000356362	15	82607

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.35e-9	0.987	125703	0	45	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	281	357	0.787	0.0000181	4371
Missense in Polyphen		77	108.39	0.71042		1342
Synonymous	-0.451	134	128	1.05	0.00000698	1206
Loss of Function	2.37	20	35.2	0.569	0.00000185	444

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000400	0.000399
Ashkenazi Jewish	0.00	0.00
East Asian	0.000168	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000213	0.000211
Middle Eastern	0.000168	0.000163
South Asian	0.000370	0.000294
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Pseudouridylate synthase that catalyzes pseudouridylation of RNAs (PubMed:28073919, PubMed:29628141). Acts as a regulator of protein synthesis in embryonic stem cells by mediating pseudouridylation of RNA fragments derived from tRNAs (tRFs): pseudouridylated tRFs inhibit translation by targeting the translation initiation complex (PubMed:29628141). Also catalyzes pseudouridylation of mRNAs: mediates pseudouridylation of mRNAs with the consensus sequence 5'-UGUAG-3' (PubMed:28073919). In addition to mRNAs and tRNAs, binds other types of RNAs, such as snRNAs, Y RNAs and vault RNAs, suggesting that it can catalyze pseudouridylation of many RNA types (PubMed:29628141). {ECO:0000269|PubMed:28073919, ECO:0000269|PubMed:29628141}.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.754
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.72

Haploinsufficiency Scores

• pHI: 0.832
• hipred: Y
• hipred_score: 0.706
• ghis: 0.632

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.337

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pus7

Gene ontology

• Biological process: negative regulation of translation;tRNA pseudouridine synthesis;regulation of hematopoietic stem cell differentiation;mRNA pseudouridine synthesis;regulation of mesoderm development
• Cellular component: nucleus
• Molecular function: RNA binding;pseudouridine synthase activity;enzyme binding