UTP4
protein-codingUTP4 small subunit processome component, the group of WD repeat domain containing|UTPa subcomplex
Gene summary
This gene encodes a WD40-repeat-containing protein that is localized to the nucleolus. Mutation of this gene causes North American Indian childhood cirrhosis, a severe intrahepatic cholestasis that results in transient neonatal jaundice, and progresses to periportal fibrosis and cirrhosis in childhood and adolescence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
- CIRH1A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~99.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0007329
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0011497
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0011497
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011497
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Gastrointestinal
Intervention: Gastrointestinal
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UTP4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032830.3. 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 | 5 | 46 | 8 | 59 | ||
| missense | 69 | 8 | 77 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 3 | |||
| Total | 0 | 0 | 77 | 54 | 9 | 140 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_116219.2 | 16 | MANE Select | |
| Ensembl | ENSP00000327179.7 | 16 | MANE Select | |
| RefSeq | NP_001305320.1 | 15 | Standard | |
| Ensembl | ENSP00000339164.4 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| utp4 | Danio rerio | Structure: hepatocyte Quality: increased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
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
Molecular Function
- RNA binding
- protein binding
Cellular Component
- fibrillar center
- nucleoplasm
- chromosome
- nucleolus
- 90S preribosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000314423
- Coding exons
- 16
- Length
- 99840
- Individuals with no LoFs
- 125716
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125748
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.160 | 367 | 376 | 0.977 | 0.0000219 | 4526 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00018 | 0.00018 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.152
Intolerance Scores
- RVIS EVS
- -0.13
- RVIS percentile EVS
- 43.98
Essentials
- Essential (gene trap)
- E