PAPPA2

pappalysin 2, the group of Pappalysins|Sushi domain containing

Basic information

Region (hg38): 1:176463170-176845601

Previous symbols: [ "PLAC3" ]

Links

ENSG00000116183 ∙ NCBI:60676 ∙ OMIM:619485 ∙ HGNC:14615 ∙ Uniprot:Q9BXP8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Short stature, Dauber-Argente type (Moderate), mode of inheritance: AR
• Short stature, Dauber-Argente type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short stature, Dauber-Argente type	AR	Endocrine	The condition can involve decreased growth, and response to prepubertal administration of growth hormone has been described	Craniofacial; Endocrine; Musculoskeletal; Neurologic	26902202; 27648969; 29029190; 34272725

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAPPA2 gene.

• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAPPA2 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	7	5	13
missense			97	8	4	109
nonsense	4					4
start loss						0
frameshift	2		1			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1		2
Total	6	0	100	16	9

Highest pathogenic variant AF is 0.0000263

Variants in PAPPA2

This is a list of pathogenic ClinVar variants found in the PAPPA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-176556338-A-G		Inborn genetic diseases	Uncertain significance (May 27, 2022)
1-176556357-C-A		Inborn genetic diseases	Uncertain significance (May 17, 2023)
1-176556455-T-A		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
1-176556467-C-T		Inborn genetic diseases	Uncertain significance (Oct 27, 2021)
1-176556602-C-T		Inborn genetic diseases	Uncertain significance (Nov 03, 2022)
1-176556711-T-A		Inborn genetic diseases	Uncertain significance (Jan 26, 2023)
1-176556767-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 24, 2024)
1-176556773-C-A		Inborn genetic diseases	Uncertain significance (Dec 14, 2022)
1-176556816-G-C		Inborn genetic diseases	Uncertain significance (May 26, 2024)
1-176556834-C-G			Benign (Dec 31, 2019)
1-176556865-C-T			Benign (Dec 31, 2019)
1-176556915-G-A		Inborn genetic diseases	Uncertain significance (May 05, 2023)
1-176556924-T-C		Inborn genetic diseases	Uncertain significance (May 09, 2022)
1-176556945-A-G		Inborn genetic diseases	Likely benign (Feb 15, 2023)
1-176556948-G-A		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
1-176556963-G-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
1-176557044-A-G		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
1-176557092-A-G		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
1-176557127-C-T		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
1-176557164-A-C		Inborn genetic diseases	Uncertain significance (Aug 26, 2022)
1-176557178-G-A		Inborn genetic diseases	Uncertain significance (Mar 29, 2024)
1-176594524-G-A		Inborn genetic diseases	Uncertain significance (Feb 08, 2023)
1-176594547-A-G		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
1-176594581-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
1-176594587-G-T		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAPPA2	protein_coding	protein_coding	ENST00000367662	22	382429

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.79e-8	1.00	124771	0	45	124816	0.000180

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.09	921	1.02e+3	0.904	0.0000583	11715
Missense in Polyphen		280	381.34	0.73426		4470
Synonymous	0.707	377	395	0.955	0.0000230	3543
Loss of Function	5.27	27	76.8	0.351	0.00000363	924

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000333	0.000333
Ashkenazi Jewish	0.000199	0.000199
East Asian	0.000111	0.000111
Finnish	0.000279	0.000278
European (Non-Finnish)	0.000195	0.000194
Middle Eastern	0.000111	0.000111
South Asian	0.0000987	0.0000980
Other	0.000166	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Metalloproteinase which specifically cleaves insulin- like growth factor binding protein (IGFBP)-5 at the '163-Ser-|- Lys-164' bond. Shows limited proteolysis toward IGFBP-3. {ECO:0000269|PubMed:11264294}.
• 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: 0.117

Intolerance Scores

• loftool: 0.594
• rvis_EVS: -1.49
• rvis_percentile_EVS: 3.62

Haploinsufficiency Scores

• pHI: 0.375
• hipred: Y
• hipred_score: 0.514
• ghis: 0.476

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.486

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pappa2
• Phenotype: craniofacial phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; immune system phenotype; skeleton phenotype; liver/biliary system phenotype; hematopoietic system 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)

Zebrafish Information Network

• Gene name: pappa2
• Affected structure: cranial neural crest cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of cell growth;proteolysis;response to salt stress;cellular protein metabolic process;bone morphogenesis
• Cellular component: extracellular region;cytosol;apical plasma membrane;extracellular exosome
• Molecular function: metalloendopeptidase activity;metallopeptidase activity;zinc ion binding