PAPSS2

3'-phosphoadenosine 5'-phosphosulfate synthase 2

Basic information

Region (hg38): 10:87659612-87747705

Links

ENSG00000198682 ∙ NCBI:9060 ∙ OMIM:603005 ∙ HGNC:8604 ∙ Uniprot:O95340 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepimetaphyseal dysplasia, PAPSS2 type (Definitive), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia, PAPSS2 type (Strong), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia, PAPSS2 type (Strong), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia, PAPSS2 type (Supportive), mode of inheritance: AR
• autosomal recessive brachyolmia (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brachyolmia 4 with mild epiphyseal and metaphyseal changes	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine; Musculoskeletal	9714015; 9771708; 19474428
The condition may include endocrinological manifestations such as premature pubarche

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAPSS2 gene.

• Spondyloepimetaphyseal dysplasia, PAPSS2 type (203 variants)
• not provided (70 variants)
• Inborn genetic diseases (18 variants)
• not specified (6 variants)
• PAPSS2-related condition (2 variants)
• Autosomal recessive brachyolmia (1 variants)
• Brachyolmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAPSS2 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			1	38	4	43
missense	1	1	95	3	3	103
nonsense	9	2				11
start loss						0
frameshift	2	3	2			7
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	3	2				5
splice region			8	5	2	15
non coding			2	29	41	72
Total	15	9	103	70	48

Highest pathogenic variant AF is 0.0000529

Variants in PAPSS2

This is a list of pathogenic ClinVar variants found in the PAPSS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-87659881-C-CGCT			Benign (Jul 27, 2020)
10-87659881-C-CGCTGCTGCT			Benign (Jun 04, 2021)
10-87659881-C-CGCTGCTGCTGCT			Likely benign (May 24, 2021)
10-87659914-C-T			Benign (May 14, 2021)
10-87660014-C-T		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Uncertain significance (Mar 23, 2020)
10-87660022-C-A		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Likely benign (Dec 06, 2022)
10-87660024-C-T		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Likely benign (Nov 11, 2022)
10-87660026-G-A		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Benign (Dec 30, 2023)
10-87660116-C-G			Benign (Jul 27, 2018)
10-87660153-A-G			Benign (Jul 27, 2018)
10-87660214-C-T			Benign (Apr 09, 2019)
10-87660300-C-T			Benign (Sep 11, 2018)
10-87709196-G-A		not specified • Spondyloepimetaphyseal dysplasia, PAPSS2 type	Benign/Likely benign (Jan 29, 2024)
10-87709196-G-T		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Pathogenic (Apr 29, 2023)
10-87709199-A-C			Uncertain significance (Jun 28, 2016)
10-87709203-A-G		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Uncertain significance (Jun 03, 2022)
10-87709205-C-G		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Uncertain significance (Dec 27, 2021)
10-87709217-A-G		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Uncertain significance (Jul 27, 2022)
10-87709227-A-G		Inborn genetic diseases	Uncertain significance (Jun 17, 2022)
10-87709228-T-C		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Likely benign (Nov 15, 2022)
10-87709233-C-T		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Uncertain significance (Jan 02, 2024)
10-87709289-C-T		Spondyloepimetaphyseal dysplasia, PAPSS2 type • PAPSS2-related disorder	Pathogenic (Nov 22, 2023)
10-87709311-C-G		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Pathogenic (May 28, 2009)
10-87709326-CAT-C		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Benign (Jan 25, 2024)
10-87709326-CATAT-C		Spondyloepimetaphyseal dysplasia, PAPSS2 type	Benign (Jan 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAPSS2	protein_coding	protein_coding	ENST00000456849	13	88093

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.97e-10	0.853	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.461	327	351	0.931	0.0000211	4062
Missense in Polyphen		133	154.13	0.8629		1731
Synonymous	-0.957	144	130	1.11	0.00000759	1217
Loss of Function	1.75	20	30.4	0.658	0.00000174	346

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000825	0.000825
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000163	0.000163
Finnish	0.000142	0.000139
European (Non-Finnish)	0.000257	0.000255
Middle Eastern	0.000163	0.000163
South Asian	0.000426	0.000425
Other	0.00	0.00

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. May have a important role in skeletogenesis during postnatal growth (By similarity). {ECO:0000250}.
• Pathway: Selenocompound metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Sulfur metabolism - Homo sapiens (human);Sulfate/Sulfite Metabolism;Sulfite oxidase deficiency;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Sulfation Biotransformation Reaction;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 (Consensus)

Recessive Scores

• pRec: 0.168

Intolerance Scores

• loftool: 0.891
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.74

Haploinsufficiency Scores

• pHI: 0.217
• hipred: Y
• hipred_score: 0.502
• ghis: 0.520

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.929

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Papss2
• Phenotype: limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; craniofacial phenotype; homeostasis/metabolism phenotype

Gene ontology

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