SUPT6H
protein-codingSPT6 homolog, histone chaperone and transcription elongation factor, the group of SH2 domain containing
Gene summary
Enables histone binding activity. Involved in transcription elongation-coupled chromatin remodeling. Predicted to be located in nucleoplasm. Predicted to be part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.5 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 SUPT6H variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003170.5. 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 | 6 | 4 | 10 | |||
| missense | 148 | 148 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 164 | 4 | 0 | 168 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003161.2 | 36 | MANE Select | |
| Ensembl | ENSP00000319104.6 | 36 | MANE Select | |
| RefSeq | NP_001307684.1 | 36 | Standard | |
| Ensembl | ENSP00000338143.4 | 36 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| supt6h | Danio rerio | Structure: pigment cell Quality: quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- RNA Polymerase II Pre-transcription Events
- Formation of RNA Pol II elongation complex
- RNA Polymerase II Transcription
- RNA Polymerase II Transcription Elongation
Biological Process
- blastocyst formation
- chromatin remodeling
- regulation of transcription, DNA-templated
- transcription by RNA polymerase II
- transcription elongation from RNA polymerase II promoter
Molecular Function
- DNA binding
- DNA-binding transcription factor activity
- RNA binding
- protein binding
- nucleosome binding
Cellular Component
- nucleus
- nucleoplasm
- transcription elongation factor complex
- transcriptionally active chromatin
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000314616
- Coding exons
- 36
- Length
- 40589
- Individuals with no LoFs
- 125744
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125748
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 5.14 | 564 | 1.03e+3 | 0.549 | 0.0000614 | 11476 |
| Missense (PolyPhen) | 85 | 266.22 | 0.31929 | 2818 | ||
| Synonymous | 0.786 | 360 | 379 | 0.949 | 0.0000219 | 3150 |
| Loss of Function | 9.17 | 4 | 106 | 0.0378 | 0.00000628 | 1114 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription elongation factor which binds histone H3 and plays a key role in the regulation of transcription elongation and mRNA processing. Enhances the transcription elongation by RNA polymerase II (RNAPII) and is also required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. Besides chaperoning histones in transcription, acts to transport and splice mRNA by forming a complex with IWS1 and the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2), to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription. SUPT6H via its association with SETD1A, regulates both class-switch recombination and somatic hypermutation through formation of H3K4me3 epigenetic marks on activation-induced cytidine deaminase (AICDA) target loci. Promotes the activation of the myogenic gene program by entailing erasure of the repressive H3K27me3 epigenetic mark through stabilization of the chromatin interaction of the H3K27 demethylase KDM6A. {ECO:0000269|PubMed:15060154, ECO:0000269|PubMed:17234882, ECO:0000269|PubMed:22316138, ECO:0000269|PubMed:23503590, ECO:0000269|PubMed:9514752}.;
Recessive Scores
- pRec
- 0.157
Intolerance Scores
- LoFtool
- 0.0216
- RVIS EVS
- -2.41
- RVIS percentile EVS
- 1.07
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.965
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |