PAPPA

pappalysin 1, the group of Pappalysins|Sushi domain containing

Basic information

Region (hg38): 9:116153791-116402321

Links

ENSG00000182752

∙ NCBI:5069 ∙ OMIM:176385 ∙ HGNC:8602 ∙ Uniprot:Q13219 ∙ 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 PAPPA gene.

not_specified (207 variants)
not_provided (13 variants)
Inborn_genetic_diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAPPA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002581.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar	3 clinvar	7
missense			198 clinvar	11 clinvar	4 clinvar	213
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	198	15	7

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAPPA	protein_coding	protein_coding	ENST00000328252	22	248519

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.161	0.839	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.21	710	897	0.792	0.0000521	10709
Missense in Polyphen		67	103.12	0.64976		1110
Synonymous	0.0896	354	356	0.994	0.0000213	3180
Loss of Function	6.01	17	72.1	0.236	0.00000369	808

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000110	0.000109
South Asian	0.0000329	0.0000327
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

Function: FUNCTION: Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is slightly inhibited by the presence of IGF. {ECO:0000269|PubMed:10077652, ECO:0000269|PubMed:10913121, ECO:0000269|PubMed:11522292}.;
Pathway: Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (Consensus)

Recessive Scores

pRec: 0.233

Intolerance Scores

loftool: 0.471
rvis_EVS: -1.4
rvis_percentile_EVS: 4.16

Haploinsufficiency Scores

pHI: 0.632
hipred: Y
hipred_score: 0.685
ghis: 0.481

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.794

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pappa
Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; skeleton phenotype;

Zebrafish Information Network

Gene name: pappaa
Affected structure: post-vent region
Phenotype tag: abnormal
Phenotype quality: kinked

Gene ontology

Biological process: proteolysis;female pregnancy;response to follicle-stimulating hormone;cellular protein metabolic process;response to glucocorticoid
Cellular component: extracellular region;extracellular space
Molecular function: metalloendopeptidase activity;metallopeptidase activity;zinc ion binding