SPP1

secreted phosphoprotein 1, the group of Receptor ligands|SIBLING family

Basic information

Region (hg38): 4:87975666-87983532

Previous symbols: [ "BNSP", "OPN" ]

Links

ENSG00000118785 ∙ NCBI:6696 ∙ OMIM:166490 ∙ HGNC:11255 ∙ Uniprot:P10451 ∙ 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 SPP1 gene.

• Inborn genetic diseases (12 variants)
• not provided (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPP1 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	2	4
missense			11	5	1	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	11	7	3

Variants in SPP1

This is a list of pathogenic ClinVar variants found in the SPP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-87976923-C-A		not specified	Uncertain significance (Dec 28, 2022)
4-87976949-A-G			Likely benign (Mar 01, 2024)
4-87977065-C-A		not specified	Uncertain significance (Jul 22, 2022)
4-87977068-G-T		not specified	Uncertain significance (Dec 19, 2023)
4-87977081-G-T		not specified	Uncertain significance (Jun 29, 2023)
4-87980070-G-A		not specified	Uncertain significance (Aug 22, 2023)
4-87980078-A-G			Benign/Likely benign (Dec 01, 2023)
4-87980121-C-A		not specified	Uncertain significance (Jan 26, 2023)
4-87981475-A-G		not specified	Uncertain significance (Sep 27, 2022)
4-87981496-G-A			Likely benign (May 24, 2018)
4-87981552-C-A			Likely benign (May 16, 2018)
4-87981577-G-A		not specified	Uncertain significance (Apr 22, 2022)
4-87981665-T-C		not specified	Uncertain significance (Dec 01, 2022)
4-87981686-C-T		not specified	Uncertain significance (Mar 01, 2024)
4-87981713-C-G		not specified	Uncertain significance (Sep 06, 2022)
4-87981736-G-A		not specified	Uncertain significance (May 31, 2023)
4-87981781-C-A			Likely benign (Dec 31, 2019)
4-87982570-G-A		not specified	Uncertain significance (Sep 01, 2023)
4-87982609-C-T		not specified	Uncertain significance (Feb 05, 2024)
4-87982632-G-A			Likely benign (May 24, 2018)
4-87982637-A-G			Likely benign (May 17, 2018)
4-87982686-A-G			Benign (Jul 05, 2018)
4-87982763-G-A		not specified	Likely benign (Sep 01, 2021)
4-87982853-G-A			Benign (Dec 31, 2019)
4-87982879-T-A		not specified	Uncertain significance (Sep 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPP1	protein_coding	protein_coding	ENST00000395080	6	7744

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000215	0.287	125536	0	212	125748	0.000843

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.281	166	177	0.940	0.00000934	2138
Missense in Polyphen		54	72.979	0.73994		939
Synonymous	0.255	65	67.7	0.961	0.00000395	544
Loss of Function	0.201	9	9.68	0.930	4.98e-7	100

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000624	0.000622
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.000509	0.000508
European (Non-Finnish)	0.00155	0.00154
Middle Eastern	0.00	0.00
South Asian	0.000164	0.000163
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Osteoclast Signaling;Osteopontin Signaling;Regulation of toll-like receptor signaling pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Human Complement System;Vitamin D Receptor Pathway;Focal Adhesion;Lung fibrosis;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;TYROBP Causal Network;Transcriptional regulation by RUNX3;PI3K-Akt Signaling Pathway;Endochondral Ossification;TGF-beta Receptor Signaling;Toll-like Receptor Signaling Pathway;Signal Transduction;regulators of bone mineralization;Post-translational protein phosphorylation;Integrin cell surface interactions;Post-translational protein modification;Metabolism of proteins;Signaling by PDGF;Extracellular matrix organization;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Beta3 integrin cell surface interactions;Degradation of the extracellular matrix;Direct p53 effectors;Signaling by Receptor Tyrosine Kinases;Osteopontin-mediated events;Alpha9 beta1 integrin signaling events;Beta1 integrin cell surface interactions;Alpha4 beta1 integrin signaling events;FGF signaling pathway;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.856

Intolerance Scores

• loftool: 0.981
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.34

Haploinsufficiency Scores

• pHI: 0.574
• hipred: N
• hipred_score: 0.398
• ghis: 0.486

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0491

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spp1
• 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); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; 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); hematopoietic system phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: spp1
• Affected structure: dermal bone
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: osteoblast differentiation;androgen catabolic process;inflammatory response;cell adhesion;embryo implantation;regulation of signaling receptor activity;extracellular matrix organization;biomineral tissue development;response to vitamin D;post-translational protein modification;cellular protein metabolic process;positive regulation of bone resorption;positive regulation of transcription, DNA-templated;decidualization;response to steroid hormone;negative regulation of collateral sprouting of intact axon in response to injury;cellular response to testosterone stimulus;positive regulation of estradiol secretion
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;Golgi apparatus;cell projection;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: cytokine activity;protein binding;extracellular matrix binding