SPP2

secreted phosphoprotein 2

Basic information

Region (hg38): 2:234050679-234077134

Links

ENSG00000072080 ∙ NCBI:6694 ∙ OMIM:602637 ∙ HGNC:11256 ∙ Uniprot:Q13103 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Limited), mode of inheritance: AD
• retinitis pigmentosa (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPP2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPP2 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			2	32	2	36
missense			74	3	2	79
nonsense			6			6
start loss						0
frameshift		1	3			4
inframe indel			3			3
splice donor/acceptor (+/-2bp)			7			7
splice region			2	6		8
non coding			2	27	3	32
Total	0	1	97	62	7

Variants in SPP2

This is a list of pathogenic ClinVar variants found in the SPP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-234050786-C-A		SPP2-related disorder	Likely benign (Jul 23, 2019)
2-234050796-A-C			Likely benign (Feb 19, 2022)
2-234050812-C-G		not specified	Uncertain significance (Aug 08, 2024)
2-234050812-C-T		not specified	Conflicting classifications of pathogenicity (Jul 30, 2024)
2-234050813-G-T			Likely benign (Apr 22, 2024)
2-234050815-T-A			Uncertain significance (Nov 04, 2023)
2-234050815-T-C			Uncertain significance (Oct 22, 2024)
2-234050834-T-C		SPP2-related disorder	Likely benign (Feb 03, 2025)
2-234050833-T-TTATG		Retinal dystrophy	Likely pathogenic (Oct 01, 2023)
2-234050836-T-C			Uncertain significance (Nov 22, 2022)
2-234050845-T-A			Uncertain significance (Dec 07, 2022)
2-234050846-TGGAATGAAC-T			Uncertain significance (Jul 26, 2023)
2-234050850-A-G			Uncertain significance (Apr 02, 2024)
2-234050855-C-T			Likely benign (Nov 13, 2021)
2-234050858-C-T			Likely benign (Nov 13, 2021)
2-234050857-A-ATGTTTGCTCTTGGAATTATGT			Uncertain significance (Nov 19, 2021)
2-234050861-G-C			Uncertain significance (Nov 19, 2021)
2-234050861-GT-CC			Uncertain significance (Feb 24, 2024)
2-234050866-G-A		not specified	Uncertain significance (Dec 26, 2023)
2-234050891-G-A			Likely benign (Jul 05, 2022)
2-234050957-G-C			Likely benign (Jan 23, 2025)
2-234050957-G-T			Likely benign (Jan 23, 2025)
2-234050962-C-A			Uncertain significance (Oct 29, 2024)
2-234050962-C-T			Likely benign (Nov 11, 2024)
2-234050963-G-A		SPP2-related disorder	Likely benign (Aug 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPP2	protein_coding	protein_coding	ENST00000168148	7	26456

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.69e-14	0.00202	125707	0	40	125747	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.389	136	124	1.10	0.00000691	1398
Missense in Polyphen		35	31.191	1.1221		369
Synonymous	0.00698	44	44.1	0.999	0.00000263	362
Loss of Function	-1.37	18	12.7	1.41	5.35e-7	160

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000630	0.000630
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000185	0.000185
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Could coordinate an aspect of bone turnover. {ECO:0000250}.
• Pathway: Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Intolerance Scores

• loftool: 0.814
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.69

Haploinsufficiency Scores

• pHI: 0.0358
• hipred: N
• hipred_score: 0.123
• ghis: 0.421

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.00449

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spp2

Gene ontology

• Biological process: skeletal system development;platelet degranulation;negative regulation of endopeptidase activity;post-translational protein modification;cellular protein metabolic process;bone remodeling
• Cellular component: extracellular region;endoplasmic reticulum lumen;platelet dense granule lumen;collagen-containing extracellular matrix
• Molecular function: endopeptidase inhibitor activity