SUPT4H1
protein-codingSPT4 homolog, DSIF elongation factor subunit
Gene summary
This gene encodes the small subunit of DRB (5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole) sensitivity-inducing factor (DSIF) complex, which regulates mRNA processing and transcription elongation by RNA polymerase II. The encoded protein is localized to the nucleus and interacts with the large subunit (SUPT5H) to form the DSIF complex. Related pseudogenes have been identified on chromosomes 2 and 12. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2012]
- SUPT4H
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SUPT4H1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003168.3. 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 | 1 | 1 | ||||
| missense | 11 | 11 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 12 | 1 | 0 | 13 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003159.1 | 5 | MANE Select | |
| Ensembl | ENSP00000225504.3 | 5 | MANE Select | |
| Ensembl | ENSP00000462100.1 | 4 | Standard | |
| Ensembl | ENSP00000462100.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Initiation of transcription and translation elongation at the HIV-1 LTR
- Disease
- Formation of the HIV-1 Early Elongation Complex
- Gene expression (Transcription)
- Formation of HIV-1 elongation complex containing HIV-1 Tat
Biological Process
- negative regulation of transcription by RNA polymerase II
- chromatin organization
- chromatin remodeling
- regulation of transcription, DNA-templated
- regulation of transcription by RNA polymerase II
Molecular Function
- RNA polymerase II complex binding
- DNA-binding transcription factor activity
- single-stranded RNA binding
- protein binding
- zinc ion binding
Cellular Component
- nucleus
- nucleoplasm
- DSIF complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000225504
- Coding exons
- 5
- Length
- 7916
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.25 | 41 | 70.4 | 0.582 | 0.00000380 | 754 |
| Missense (PolyPhen) | 12 | 22.953 | 0.52281 | 269 | ||
| Synonymous | 1.36 | 18 | 27.0 | 0.667 | 0.00000139 | 225 |
| Loss of Function | 1.11 | 6 | 9.76 | 0.615 | 6.50e-7 | 90 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites. DSIF can also positively regulate transcriptional elongation and is required for the efficient activation of transcriptional elongation by the HIV- 1 nuclear transcriptional activator, Tat. DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences. {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9857195}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.448
- RVIS EVS
- 0.21
- RVIS percentile EVS
- 67.72
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.982
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |