USB1

U6 snRNA biogenesis phosphodiesterase 1

Basic information

Region (hg38): 16:57999545-58021618

Previous symbols: [ "C16orf57" ]

Links

ENSG00000103005 ∙ NCBI:79650 ∙ OMIM:613276 ∙ HGNC:25792 ∙ Uniprot:Q9BQ65 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• poikiloderma with neutropenia (Definitive), mode of inheritance: AR
• dyskeratosis congenita (Supportive), mode of inheritance: AD
• poikiloderma with neutropenia (Supportive), mode of inheritance: AR
• poikiloderma with neutropenia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Poikiloderma with neutropenia	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious; Dermatologic	18925663; 20004881; 20503306
Individuals may also be at risk for leukemia and related processes

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USB1 gene.

• not provided (235 variants)
• Poikiloderma with neutropenia (27 variants)
• not specified (14 variants)
• Inborn genetic diseases (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USB1 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				41	1	42
missense		2	95	2	1	100
nonsense	3					3
start loss			3			3
frameshift	6	2				8
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	5				6
splice region			6	6		12
non coding			2	39	18	59
Total	10	9	101	82	20

Highest pathogenic variant AF is 0.0000329

Variants in USB1

This is a list of pathogenic ClinVar variants found in the USB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-58001290-C-G			Likely benign (May 16, 2021)
16-58001305-T-G			Likely benign (Jun 23, 2021)
16-58001433-G-C			Likely benign (Feb 24, 2021)
16-58001479-G-GC			Uncertain significance (Apr 26, 2021)
16-58001484-A-G		Poikiloderma with neutropenia	Uncertain significance (Apr 07, 2022)
16-58001486-G-C			Uncertain significance (Jul 10, 2022)
16-58001489-C-T			Likely benign (Aug 10, 2023)
16-58001494-C-A			Uncertain significance (May 17, 2021)
16-58001494-C-G			Uncertain significance (Oct 04, 2021)
16-58001495-GC-G			Pathogenic (Jun 26, 2022)
16-58001501-G-A			Likely benign (Dec 13, 2023)
16-58001503-T-C		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
16-58001506-G-A		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
16-58001511-A-G			Uncertain significance (Aug 22, 2021)
16-58001513-C-T			Likely benign (Jan 02, 2024)
16-58001525-C-A		not specified	Benign (Feb 01, 2024)
16-58001528-G-T			Uncertain significance (Aug 28, 2021)
16-58001530-A-G			Uncertain significance (Oct 27, 2021)
16-58001541-G-A			Uncertain significance (Oct 17, 2022)
16-58001543-CG-C		Poikiloderma with neutropenia	Pathogenic/Likely pathogenic (Oct 09, 2023)
16-58001544-G-A			Uncertain significance (Oct 20, 2022)
16-58001544-G-C		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
16-58001557-G-A			Uncertain significance (Dec 19, 2019)
16-58001557-G-C		Inborn genetic diseases	Uncertain significance (Oct 01, 2023)
16-58001558-G-A			Likely benign (Dec 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USB1	protein_coding	protein_coding	ENST00000219281	7	22073

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000687	0.923	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.192	147	154	0.956	0.00000921	1736
Missense in Polyphen		46	45.508	1.0108		526
Synonymous	-0.823	69	60.8	1.13	0.00000356	516
Loss of Function	1.57	7	13.2	0.532	6.56e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000304
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000411	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.000144	0.000141
Middle Eastern	0.000411	0.000381
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Phosphodiesterase responsible for the U6 snRNA 3' end processing. Acts as an exoribonuclease (RNase) responsible for trimming the poly(U) tract of the last nucleotides in the pre-U6 snRNA molecule, leading to the formation of mature U6 snRNA 3' end-terminated with a 2',3'-cyclic phosphate. {ECO:0000255|HAMAP- Rule:MF_03040, ECO:0000269|PubMed:22899009, ECO:0000269|PubMed:23190533}.
• Disease: DISEASE: Poikiloderma with neutropenia (PN) [MIM:604173]: A genodermatosis characterized by poikiloderma, pachyonychia and chronic neutropenia. The disorder starts as a papular erythematous rash on the limbs during the first year of life. It gradually spreads centripetally and, as the papular rash resolves, hypo- and hyperpigmentation result, with development of telangiectasias. Another skin manifestation is pachyonychia, but alopecia and leukoplakia are distinctively absent. Patients have recurrent pneumonias that usually result in reactive airway disease and/or chronic cough. One of the most important extracutaneous symptoms is an increased susceptibility to infections, mainly affecting the respiratory system, primarily due to a chronic neutropenia and to neutrophil functional defects. Bone marrow abnormalities account for neutropenia and may evolve into myelodysplasia associated with the risk of leukemic transformation. Poikiloderma with neutropenia shows phenotypic overlap with Rothmund-Thomson syndrome. {ECO:0000269|PubMed:20004881, ECO:0000269|PubMed:20503306}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0975

Intolerance Scores

• rvis_EVS: 0.19
• rvis_percentile_EVS: 67.03

Haploinsufficiency Scores

• pHI: 0.0943
• hipred: N
• hipred_score: 0.332
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usb1

Zebrafish Information Network

• Gene name: usb1
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: RNA splicing;U6 snRNA 3'-end processing;RNA phosphodiester bond hydrolysis, exonucleolytic
• Cellular component: nucleus;intercellular bridge
• Molecular function: 3'-5'-exoribonuclease activity;poly(U)-specific exoribonuclease activity, producing 3' uridine cyclic phosphate ends