UTP4

UTP4 small subunit processome component, the group of WD repeat domain containing|UTPa subcomplex

Basic information

Region (hg38): 16:69131291-69231130

Previous symbols: [ "CIRH1A" ]

Links

ENSG00000141076 ∙ NCBI:84916 ∙ OMIM:607456 ∙ HGNC:1983 ∙ Uniprot:Q969X6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary North American Indian childhood cirrhosis (Supportive), mode of inheritance: AR
• cirrhosis, familial (Disputed Evidence), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
North American Indian childhood cirrhosis	AR	Gastrointestinal	Individuals may initially present with neonatal cholestatic jaundice, and the condition may progress to end-stage, severe liver failure; Liver transplantation has been described as effective, and individuals have been described as dying before liver transplantation was available	Gastrointestinal	6894906; 10820129; 11045837

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UTP4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UTP4 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			6	28	7	41
missense			38	4	2	44
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	5		7
non coding			2	4	2	8
Total	0	0	47	36	11

Variants in UTP4

This is a list of pathogenic ClinVar variants found in the UTP4 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-69133455-T-C		Hereditary North American Indian childhood cirrhosis	Uncertain significance (Jan 12, 2018)
16-69133495-T-C		UTP4-related disorder	Likely benign (Jun 03, 2022)
16-69133516-C-A		Hereditary North American Indian childhood cirrhosis	Uncertain significance (Jan 13, 2018)
16-69133533-A-G		UTP4-related disorder • not specified	Uncertain significance (Apr 06, 2023)
16-69133552-G-A		UTP4-related disorder	Likely benign (Mar 24, 2024)
16-69133557-T-C			Uncertain significance (Jul 17, 2023)
16-69133574-A-G		UTP4-related disorder	Uncertain significance (Oct 19, 2023)
16-69136751-A-G			Uncertain significance (May 23, 2023)
16-69136774-A-C		UTP4-related disorder	Uncertain significance (Jun 23, 2023)
16-69136780-G-A			Uncertain significance (Jul 03, 2022)
16-69136806-G-A		Hereditary North American Indian childhood cirrhosis	Benign (Jan 16, 2024)
16-69136838-G-T		Hereditary North American Indian childhood cirrhosis • UTP4-related disorder	Conflicting classifications of pathogenicity (Dec 21, 2023)
16-69136881-A-G		UTP4-related disorder	Likely benign (Apr 12, 2023)
16-69137867-A-G		Hereditary North American Indian childhood cirrhosis	Uncertain significance (Jan 12, 2018)
16-69137876-C-T		not specified • UTP4-related disorder	Uncertain significance (Oct 26, 2021)
16-69137892-G-A		UTP4-related disorder	Likely benign (May 03, 2024)
16-69139852-C-A		UTP4-related disorder	Likely benign (Jan 25, 2024)
16-69139853-C-T			Likely benign (May 31, 2023)
16-69139866-A-G		UTP4-related disorder	Uncertain significance (Dec 07, 2023)
16-69143182-C-T		Hereditary North American Indian childhood cirrhosis	Uncertain significance (Jan 13, 2018)
16-69143185-T-C		UTP4-related disorder	Likely benign (May 10, 2022)
16-69143186-G-T		UTP4-related disorder	Likely benign (May 23, 2023)
16-69143221-C-T			Likely benign (Jun 27, 2023)
16-69143222-G-A			Uncertain significance (Apr 24, 2023)
16-69143226-C-G		UTP4-related disorder	Uncertain significance (Mar 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UTP4	protein_coding	protein_coding	ENST00000314423	16	99840

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.71e-7	1.00	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.160	367	376	0.977	0.0000219	4526
Missense in Polyphen		71	96.353	0.73688		1166
Synonymous	-1.39	154	134	1.15	0.00000785	1315
Loss of Function	3.25	17	38.9	0.437	0.00000235	414

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.000185	0.000185
European (Non-Finnish)	0.0000968	0.0000967
Middle Eastern	0.000163	0.000163
South Asian	0.000295	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ribosome biogenesis factor. Involved in nucleolar processing of pre-18S ribosomal RNA. Involved in small subunit (SSU) pre-rRNA processing at sites A', A0, 1 and 2b. Required for optimal pre-ribosomal RNA transcription by RNA polymerase (PubMed:17699751, PubMed:19732766). May be a transcriptional regulator. Acts as a positive regulator of HIVEP1 which specifically binds to the DNA sequence 5'-GGGACTTTCC-3' found in enhancer elements of numerous viral promoters such as those of HIV-1, SV40, or CMV (PubMed:19732766). {ECO:0000269|PubMed:17699751, ECO:0000269|PubMed:19732766, ECO:0000269|PubMed:22916032}.
• Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human);rRNA processing;Metabolism of RNA;rRNA modification in the nucleus and cytosol;rRNA processing in the nucleus and cytosol (Consensus)

Recessive Scores

• pRec: 0.152

Intolerance Scores

• rvis_EVS: -0.13
• rvis_percentile_EVS: 43.98

Haploinsufficiency Scores

• pHI: 0.443
• hipred: Y
• hipred_score: 0.694
• ghis: 0.559

Essentials

• essential_gene_gene_trap: E

Mouse Genome Informatics

• Gene name: Utp4

Zebrafish Information Network

• Gene name: utp4
• Affected structure: hepatocyte
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);regulation of transcription, DNA-templated;rRNA processing;maturation of SSU-rRNA
• Cellular component: fibrillar center;nucleoplasm;chromosome;nucleolus;90S preribosome;small-subunit processome;t-UTP complex
• Molecular function: RNA binding;protein binding