PAPSS1

3'-phosphoadenosine 5'-phosphosulfate synthase 1

Basic information

Region (hg38): 4:107590275-107720234

Links

ENSG00000138801 ∙ NCBI:9061 ∙ OMIM:603262 ∙ HGNC:8603 ∙ Uniprot:O43252 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAPSS1 gene.

• Inborn genetic diseases (30 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAPSS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			30			30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	30	0	0

Variants in PAPSS1

This is a list of pathogenic ClinVar variants found in the PAPSS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-107614260-C-T		not specified	Uncertain significance (Aug 12, 2021)
4-107614269-T-G		not specified	Uncertain significance (Nov 17, 2022)
4-107614301-G-A		not specified	Uncertain significance (Aug 01, 2022)
4-107614323-G-T		not specified	Uncertain significance (Jun 21, 2022)
4-107614337-C-T		not specified	Uncertain significance (Nov 18, 2022)
4-107614377-A-G		not specified	Uncertain significance (Dec 02, 2022)
4-107631695-C-T		not specified	Uncertain significance (Mar 02, 2023)
4-107631779-G-T		not specified	Uncertain significance (Jul 26, 2022)
4-107644804-C-T		not specified	Uncertain significance (May 17, 2023)
4-107644863-T-G		not specified	Uncertain significance (Jul 14, 2022)
4-107644893-T-C		not specified	Uncertain significance (May 05, 2023)
4-107644895-C-G		not specified	Uncertain significance (May 18, 2022)
4-107644906-G-A		not specified	Uncertain significance (Jul 25, 2023)
4-107644918-G-A		not specified	Uncertain significance (Jan 31, 2023)
4-107644926-T-C		not specified	Uncertain significance (Jan 06, 2023)
4-107644939-A-G		not specified	Uncertain significance (Dec 21, 2022)
4-107644974-C-T		not specified	Uncertain significance (Jan 11, 2023)
4-107644975-G-A		not specified	Uncertain significance (Aug 30, 2021)
4-107644981-C-T		not specified	Uncertain significance (Jan 26, 2022)
4-107653500-T-C		not specified	Uncertain significance (Aug 25, 2021)
4-107653554-C-T		not specified	Uncertain significance (Feb 27, 2023)
4-107653577-A-C		not specified	Uncertain significance (Jun 24, 2022)
4-107654777-T-C		not specified	Uncertain significance (Dec 07, 2023)
4-107654781-G-A		not specified	Uncertain significance (Jan 03, 2024)
4-107654796-G-A		not specified	Uncertain significance (Jun 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAPSS1	protein_coding	protein_coding	ENST00000265174	12	130176

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.33e-8	0.994	125527	0	221	125748	0.000879

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.74	263	355	0.740	0.0000192	4088
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000445	0.000445
Ashkenazi Jewish	0.0141	0.0142
East Asian	0.000382	0.000381
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000375	0.000369
Middle Eastern	0.000382	0.000381
South Asian	0.000392	0.000392
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Selenocompound metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Sulfur metabolism - Homo sapiens (human);Selenoamino Acid Metabolism;Sulfation Biotransformation Reaction;Disease;Metabolism of ingested H2SeO4 and H2SeO3 into H2Se;Transport and synthesis of PAPS;Metabolism of carbohydrates;Phase II - Conjugation of compounds;Glycosaminoglycan metabolism;sulfate activation for sulfonation;Metabolism of amino acids and derivatives;Biological oxidations;Metabolism;Selenoamino acid metabolism;Cytosolic sulfonation of small molecules;Purine nucleotides nucleosides metabolism;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.168

Intolerance Scores

• loftool: 0.755
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.46

Haploinsufficiency Scores

• pHI: 0.369
• hipred: N
• hipred_score: 0.454
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.990

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Papss1

Gene ontology

• Biological process: sulfate assimilation;skeletal system development;phosphorylation;3'-phosphoadenosine 5'-phosphosulfate biosynthetic process
• Cellular component: cytosol
• Molecular function: adenylylsulfate kinase activity;sulfate adenylyltransferase (ATP) activity;ATP binding;nucleotidyltransferase activity;protein homodimerization activity