USB1 (U6 snRNA biogenesis phosphodiesterase 1)

Gene

• Entrez ID: 79650
• Gene name: U6 snRNA biogenesis phosphodiesterase 1
• Gene symbol: USB1
• Synonyms (NCBI Gene): C16orf57, HVSL1, Mpn1, PN, hMpn1, hUsb1
• Chromosome: 16
• Chromosome location: 16q21
• Summary: This gene encodes a protein with several conserved domains, however, its exact function is not known. Mutations in this gene are associated with poikiloderma with neutropenia (PN), which shows phenotypic overlap with Rothmund-Thomson syndrome (RTS) caused

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137853970	A>C	Pathogenic	Genic downstream transcript variant, splice acceptor variant
rs137853971	A>G	Pathogenic	Intron variant, coding sequence variant, genic downstream transcript variant, missense variant
rs137853972	AGGAACTACAGG>-	Pathogenic	Genic downstream transcript variant, coding sequence variant, splice donor variant
rs771096742	T>A,C	Pathogenic	Coding sequence variant, stop gained, synonymous variant
rs777667891	TCAA>-	Pathogenic	Genic downstream transcript variant, frameshift variant, intron variant, coding sequence variant
rs1249059283	A>C,G	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs1292827495	G>T	Pathogenic	Splice donor variant, genic downstream transcript variant
rs1459714680	C>T	Pathogenic	Genic downstream transcript variant, coding sequence variant, stop gained
rs1555498092	G>A	Pathogenic	Splice acceptor variant
rs1555498117	->C	Pathogenic	Frameshift variant, coding sequence variant
rs1555498120	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1555498129	C>T	Pathogenic	Stop gained, coding sequence variant
rs1555498396	A>G	Pathogenic	Intron variant, genic downstream transcript variant, splice acceptor variant
rs1555498399	A>-	Pathogenic	Frameshift variant, intron variant, genic downstream transcript variant, coding sequence variant
rs1555498563	T>G	Pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant
rs1555498565	A>-	Pathogenic	Frameshift variant, genic downstream transcript variant, coding sequence variant
rs1555498573	C>T	Pathogenic	Stop gained, genic downstream transcript variant, coding sequence variant
rs1555498581	G>A	Pathogenic	Splice donor variant, genic downstream transcript variant
rs1597049287	T>C	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT028794	hsa-miR-26b-5p	Microarray	19088304
MIRT050173	hsa-miR-26a-5p	CLASH	23622248
MIRT491593	hsa-miR-4524b-3p	PAR-CLIP	23592263
MIRT491591	hsa-miR-6758-5p	PAR-CLIP	23592263
MIRT491592	hsa-miR-6856-5p	PAR-CLIP	23592263
MIRT491590	hsa-miR-3125	PAR-CLIP	23592263
MIRT491589	hsa-miR-3916	PAR-CLIP	23592263
MIRT491588	hsa-miR-6859-5p	PAR-CLIP	23592263
MIRT491587	hsa-miR-4779	PAR-CLIP	23592263
MIRT491586	hsa-miR-4524a-3p	PAR-CLIP	23592263
MIRT491585	hsa-miR-3150b-3p	PAR-CLIP	23592263
MIRT491584	hsa-miR-4784	PAR-CLIP	23592263
MIRT491583	hsa-miR-6077	PAR-CLIP	23592263
MIRT491582	hsa-miR-185-5p	PAR-CLIP	23592263
MIRT491581	hsa-miR-4306	PAR-CLIP	23592263
MIRT491580	hsa-miR-4644	PAR-CLIP	23592263
MIRT491579	hsa-miR-765	PAR-CLIP	23592263
MIRT491577	hsa-miR-7106-5p	PAR-CLIP	23592263
MIRT491578	hsa-miR-6825-5p	PAR-CLIP	23592263
MIRT491593	hsa-miR-4524b-3p	PAR-CLIP	23592263
MIRT491591	hsa-miR-6758-5p	PAR-CLIP	23592263
MIRT491592	hsa-miR-6856-5p	PAR-CLIP	23592263
MIRT491590	hsa-miR-3125	PAR-CLIP	23592263
MIRT491589	hsa-miR-3916	PAR-CLIP	23592263
MIRT491588	hsa-miR-6859-5p	PAR-CLIP	23592263
MIRT491587	hsa-miR-4779	PAR-CLIP	23592263
MIRT491586	hsa-miR-4524a-3p	PAR-CLIP	23592263
MIRT491585	hsa-miR-3150b-3p	PAR-CLIP	23592263
MIRT491584	hsa-miR-4784	PAR-CLIP	23592263
MIRT491583	hsa-miR-6077	PAR-CLIP	23592263
MIRT491582	hsa-miR-185-5p	PAR-CLIP	23592263
MIRT491581	hsa-miR-4306	PAR-CLIP	23592263
MIRT491580	hsa-miR-4644	PAR-CLIP	23592263
MIRT491579	hsa-miR-765	PAR-CLIP	23592263
MIRT491577	hsa-miR-7106-5p	PAR-CLIP	23592263
MIRT491578	hsa-miR-6825-5p	PAR-CLIP	23592263

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000175	Function	3'-5'-RNA exonuclease activity	IBA
GO:0000175	Function	3'-5'-RNA exonuclease activity	IDA	23190533, 30215753
GO:0000175	Function	3'-5'-RNA exonuclease activity	IEA
GO:0004518	Function	Nuclease activity	IEA
GO:0005515	Function	Protein binding	IPI	23022480
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	22899009, 23022480
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0008380	Process	RNA splicing	IMP	22899009
GO:0016787	Function	Hydrolase activity	IEA
GO:0016829	Function	Lyase activity	IEA
GO:0034472	Process	SnRNA 3'-end processing	IMP	26213367
GO:0034477	Process	U6 snRNA 3'-end processing	IBA
GO:0034477	Process	U6 snRNA 3'-end processing	IDA	23190533
GO:0034477	Process	U6 snRNA 3'-end processing	IEA
GO:0034477	Process	U6 snRNA 3'-end processing	IMP	22899009, 23022480, 26213367
GO:0045171	Component	Intercellular bridge	IDA
GO:1990838	Function	Poly(U)-specific exoribonuclease activity, producing 3' uridine cyclic phosphate ends	IDA	23022480, 23190533, 26213367, 28887445, 31832688
GO:1990838	Function	Poly(U)-specific exoribonuclease activity, producing 3' uridine cyclic phosphate ends	IEA

Other IDs

• MIM: 613276
• HGNC: 25792
• e!Ensembl: ENSG00000103005

Protein

• UniProt ID: Q9BQ65
• Protein name: U6 snRNA phosphodiesterase 1 (hUsb1) (3'-5' RNA exonuclease USB1) (EC 4.6.1.-) (Mutated in poikiloderma with neutropenia protein 1) (Mutated in PN protein 1) (hMpn1)
• Protein function: 3'-5' RNA exonuclease that trims the 3' end of oligo(U) and oligo(A) tracts of the pre-U6 small nuclear RNA (snRNA) molecule, leading to the formation of a mature U6 snRNA 3' end-terminated with a 2',3'-cyclic phosphate (PubMed:22899009, PubMed:
• PDB: 4H7W, 5V1M, 6D2Z, 6D30, 6D31
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF09749	HVSL	43 → 263	Uncharacterised conserved protein	Family

• Sequence:

  MSAAPLVGYSSSGSEDESEDGMRTRPGDGSHRRGQSPLPRQRFPVPDSVLNMFPGTEEGP
  EDDSTKHGGRVRTFPHERGNWATHVYVPYEAKEEFLDLLDVLLPHAQTYVPRLVRMKVFH
  LSLSQSVVLRHHWILPFVQALKARMTSFHRFFFTANQVKIYTNQEKTRTFIGLEVTSGHA
  QFLDLVSEVDRVMEEFNLTTFYQDPSFHLSLAWCVGDARLQLEGQCLQELQAIVDGFEDA
  EVLLRVHTEQVRCKSGNKFFSMPLK

• Sequence length: 265

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
Poikiloderma with neutropenia	Likely pathogenic; Pathogenic	rs747958554, rs137853970, rs137853972, rs137853971, rs137853973, rs786205051, rs1555498399, rs1555498565, rs1555498573, rs1249059283, rs1459714680, rs1292827495, rs759761915, rs1555498092, rs1555498129, rs777667891, rs1555498120, rs1597049287	RCV002504642 RCV000000224 RCV000000225 RCV000000226 RCV000144431 RCV000000227 RCV000598668 RCV000598696 RCV000599164 RCV000599396 RCV000598691 RCV000599560 RCV000598852 RCV000599282 RCV000599306 RCV000598593 RCV000677661 RCV000985173	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
USB1-related disorder	Likely pathogenic; Pathogenic	rs747958554	RCV004758163	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DYSKERATOSIS CONGENITA	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alopecia	Alopecia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	26872609	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	26872609	Associate	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	Pubtator	32020235	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cirrhosis	Cirrhosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Conjunctivitis	Conjunctivitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dermatologic disorders	Dermatologic Disorders	BEFREE	23776162		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dubowitz syndrome	Dubowitz syndrome	Pubtator	27612988	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyskeratosis Congenita	Dyskeratosis Congenita	GENOMICS_ENGLAND_DG	20004881		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyskeratosis Congenita	Dyskeratosis Congenita	BEFREE	20817924, 21872685, 22899009, 26535771, 27612988		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyskeratosis Congenita	Dyskeratosis Congenita	ORPHANET_DG	20817924, 22160078		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyskeratosis Congenita	Dyskeratosis congenita	Pubtator	20817924, 22899009, 27612988	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyskeratosis congenita	Dyskeratosis Congenita	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dystonic Disorders	Dystonia	Pubtator	26306619	Associate	★☆☆☆☆ Found in Text Mining only
Dystrophia unguium	Nail dystrophy	BEFREE	21872685		★☆☆☆☆ Found in Text Mining only
Dystrophia unguium	Nail dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ectodermal Dysplasia	Ectodermal dysplasia	Pubtator	27612988	Associate	★☆☆☆☆ Found in Text Mining only
Ectrodactyly	Ectrodactyly	Pubtator	26546903	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Stenosis	Esophageal Stenosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gingivitis	Gingivitis	BEFREE	21872685		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	27612988	Associate	★☆☆☆☆ Found in Text Mining only
Hypodontia	Hypodontia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of the maxilla	Hypoplasia of the maxilla	HPO_DG			★☆☆☆☆ Found in Text Mining only
Keratoderma, Palmoplantar	Palmoplantar keratoderma	BEFREE	21872685		★☆☆☆☆ Found in Text Mining only
Keratoderma, Palmoplantar	Palmoplantar keratoderma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	37164308	Associate	★☆☆☆☆ Found in Text Mining only
Leukopenia	Leukopenia	BEFREE	20817924, 21872685		★☆☆☆☆ Found in Text Mining only
Leukoplakia, Oral	Leukoplakia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver Failure	Liver failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lung Diseases	Lung disease	Pubtator	26273833	Associate	★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malabsorption Syndrome	Malabsorption Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	26306619		★☆☆☆☆ Found in Text Mining only
Myelodysplasia	Myelodysplasia	BEFREE	26306619		★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	26306619		★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndromes	Myelodysplastic syndrome	Pubtator	26306619	Associate	★☆☆☆☆ Found in Text Mining only
Myelodysplastic-Myeloproliferative Diseases	Myelodysplastic-Myeloproliferative Diseases	BEFREE	26306619		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural tube defect	Pubtator	26306619	Associate	★☆☆☆☆ Found in Text Mining only
Neutropenia	Neutropenia	BEFREE	20817924, 21872685		★☆☆☆☆ Found in Text Mining only
Neutropenia	Neutropenia	Pubtator	20817924, 22899009, 26213367, 26987923, 27612988, 35522049	Associate	★☆☆☆☆ Found in Text Mining only
Neutropenia	Neutropenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	27028305	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasm	Pancreatic Neoplasm	HPO_DG			★☆☆☆☆ Found in Text Mining only
Periodontitis	Periodontitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Poikiloderma	Poikiloderma	BEFREE	20817924, 21872685		★☆☆☆☆ Found in Text Mining only
Poikiloderma	Poikiloderma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Poikiloderma with Neutropenia	Poikiloderma With Neutropenia	BEFREE	20004881, 20734427, 20817924, 21271650, 21967010, 22269211, 22899009, 23022480, 23190533, 23196894, 23776162, 26213367, 26306619, 26522474, 26546903, 27612988, 28353165, 29797650, 30215753		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Poikiloderma with Neutropenia	Poikiloderma With Neutropenia	CLINVAR_DG	20004881, 20618321, 20817924, 21271650, 21872685		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Poikiloderma with Neutropenia	Poikiloderma With Neutropenia	ORPHANET_DG	20004881, 20503306		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Poikiloderma with Neutropenia	Poikiloderma With Neutropenia	GENOMICS_ENGLAND_DG	20004881, 20503306, 25044170		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Poikiloderma with neutropenia	Poikiloderma With Neutropenia	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Poikiloderma with Neutropenia	Poikiloderma With Neutropenia	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Recurrent otitis media	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Recurrent sinusitis	Sinusitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rett Syndrome	Rett syndrome	Pubtator	20817924	Associate	★☆☆☆☆ Found in Text Mining only
Rothmund-Thomson syndrome	Rothmund-Thomson Syndrome	BEFREE	20817924, 22899009		★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	24887023	Inhibit	★☆☆☆☆ Found in Text Mining only
Taurodontism	Taurodontism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	BEFREE	22269211		★☆☆☆☆ Found in Text Mining only