PAPSS1
protein-coding3'-phosphoadenosine 5'-phosphosulfate synthase 1
Gene summary
Three-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS) is the sulfate donor cosubstrate for all sulfotransferase (SULT) enzymes (Xu et al., 2000 [PubMed 10679223]). SULTs catalyze the sulfate conjugation of many endogenous and exogenous compounds, including drugs and other xenobiotics. In humans, PAPS is synthesized from adenosine 5-prime triphosphate (ATP) and inorganic sulfate by 2 isoforms, PAPSS1 and PAPSS2 (MIM 603005).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~130.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011122
Submitter: LiferaOmics
Genetic evidence – Published PMID: 37644014 – Reports one affected individual. Case-level (biallelic non-LOF in AR model; homozygous; no deduction applied) (Founder variant, 10 affected members) Variant level score= 1 Segregation score= 3 Our Cases Total = 4 / 12 Experimental Evidence – Published Gene function/biochemical evidence: PMID 10679223, 22451673, and the classic enzymology papers (9576487, 9668121, 14747722). animal model undergoing validation Experimental evidence = 3 Updated total = 7
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PAPSS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005443.5. 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 | 1 | 1 | ||||
| missense | 70 | 70 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 75 | 0 | 0 | 75 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005434.4 | 12 | MANE Select | |
| Ensembl | ENSP00000265174.4 | 12 | MANE Select | |
| Ensembl | ENSP00000543455.1 | 13 | Standard | |
| Ensembl | ENSP00000543455.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Selenocompound metabolism - Homo sapiens (human)
- Purine metabolism - Homo sapiens (human)
- Sulfur metabolism - Homo sapiens (human)
- Selenoamino Acid Metabolism
- Sulfation Biotransformation Reaction
Biological Process
- sulfate assimilation
- skeletal system development
- phosphorylation
- 3'-phosphoadenosine 5'-phosphosulfate biosynthetic process
Molecular Function
- adenylylsulfate kinase activity
- sulfate adenylyltransferase (ATP) activity
- ATP binding
- nucleotidyltransferase activity
- protein homodimerization activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265174
- Coding exons
- 12
- Length
- 130176
- Individuals with no LoFs
- 125527
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 221
- Defined
- 125748
- p
- 0.000879
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.74 | 263 | 355 | 0.740 | 0.0000192 | 4088 |
| Missense (PolyPhen) | 108 | 156.71 | 0.68919 | 1697 | ||
| Synonymous | -0.107 | 122 | 121 | 1.01 | 0.00000605 | 1192 |
| Loss of Function | 2.48 | 17 | 32.2 | 0.528 | 0.00000183 | 365 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.014 | 0.014 | notable |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00038 | 0.00037 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate (PAPS: activated sulfate donor used by sulfotransferase). In mammals, PAPS is the sole source of sulfate; APS appears to be only an intermediate in the sulfate- activation pathway (PubMed:9576487, PubMed:9668121, PubMed:9648242, PubMed:14747722). Required for normal biosynthesis of sulfated L-selectin ligands in endothelial cells (PubMed:9576487). {ECO:0000269|PubMed:14747722, ECO:0000269|PubMed:9576487, ECO:0000269|PubMed:9648242, ECO:0000269|PubMed:9668121}.;
Recessive Scores
- pRec
- 0.168
Intolerance Scores
- LoFtool
- 0.755
- RVIS EVS
- -0.8
- RVIS percentile EVS
- 12.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.990
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |