SSRP1
protein-codingstructure specific recognition protein 1
Gene summary
The protein encoded by this gene is a subunit of a heterodimer that, along with SUPT16H, forms chromatin transcriptional elongation factor FACT. FACT interacts specifically with histones H2A/H2B to effect nucleosome disassembly and transcription elongation. FACT and cisplatin-damaged DNA may be crucial to the anticancer mechanism of cisplatin. This encoded protein contains a high mobility group box which most likely constitutes the structure recognition element for cisplatin-modified DNA. This protein also functions as a co-activator of the transcriptional activator p63. An alternatively spliced transcript variant of this gene has been described, but its full-length nature is not known. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.9 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 SSRP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003146.3. 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 | 2 | 3 | 5 | |||
| missense | 55 | 2 | 57 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 66 | 2 | 3 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003137.1 | 16 | MANE Select | |
| Ensembl | ENSP00000278412.2 | 16 | MANE Select | |
| Ensembl | ENSP00000431154.2 | 4 | Standard | |
| Ensembl | ENSP00000434546.2 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ssrp1a | Danio rerio | Structure: head Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Disease
- Gene expression (Transcription)
- Formation of HIV-1 elongation complex containing HIV-1 Tat
- Tat-mediated elongation of the HIV-1 transcript
- HIV Transcription Elongation
Biological Process
- DNA replication
- DNA repair
- regulation of transcription by RNA polymerase II
- transcription by RNA polymerase II
- transcription elongation from RNA polymerase II promoter
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- chromatin binding
- RNA binding
- protein binding
Cellular Component
- nucleoplasm
- chromosome
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000278412
- Coding exons
- 16
- Length
- 9893
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125748
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.04 | 189 | 423 | 0.447 | 0.0000251 | 4730 |
| Missense (PolyPhen) | 24 | 107.16 | 0.22396 | 1271 | ||
| Synonymous | 1.25 | 134 | 154 | 0.872 | 0.00000906 | 1281 |
| Loss of Function | 4.98 | 5 | 38.3 | 0.131 | 0.00000204 | 456 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). Binds specifically to double-stranded DNA and at low levels to DNA modified by the antitumor agent cisplatin. May potentiate cisplatin-induced cell death by blocking replication and repair of modified DNA. Also acts as a transcriptional coactivator for p63/TP63. {ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:12374749, ECO:0000269|PubMed:12934006, ECO:0000269|PubMed:16713563, ECO:0000269|PubMed:9489704, ECO:0000269|PubMed:9566881, ECO:0000269|PubMed:9836642}.;
Recessive Scores
- pRec
- 0.193
Intolerance Scores
- LoFtool
- 0.0641
- RVIS EVS
- -0.76
- RVIS percentile EVS
- 13.45
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.846
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |