SPP2

protein-coding

secreted phosphoprotein 2

Gene summary

This gene encodes a secreted phosphoprotein that is a member of the cystatin superfamily. [provided by RefSeq, Oct 2008]

MANE transcript

NM_006944.3

Inheritance

ClinVar variants

P:2U:112B:56

Top phenotype

Retinal dystrophy

gnomAD constraint

pLI —, LoF o/e 1.41

Max pathogenic AF

—

Genomic locus

chr2:234,050,679-234,077,134

External References & Databases

Ensembl (ENSG00000072080)

Transcript & Mutation Effects

hg38 • Region Span ~26.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

retinitis pigmentosaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: Franklin by Genoox

In a Chinese family with autosomal dominant RP, a putative pathogenic variant, p.Gly97Arg, in the gene SPP2 was identified

retinitis pigmentosaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPP2 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 196

not specifiedTotal: 59

Retinal dystrophyTotal: 15

SPP2-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006944.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	41 clinvar	1 clinvar	44
missense		1 clinvar	90 clinvar	12 clinvar	2 clinvar	105
nonsense			6 clinvar			6
start loss						0
frameshift		1 clinvar	4 clinvar			5
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	2	112	53	3	170

Highest pathogenic variant AF is 6.8409184e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006944.3	RefSeq	NP_008875.1	7	MANE Select
ENST00000168148.8	Ensembl	ENSP00000168148.3	7	MANE Select
ENST00000373368.5	Ensembl	ENSP00000362466.1	7	Standard
ENST00000373368.6	Ensembl	ENSP00000362466.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

skeletal system development
platelet degranulation
negative regulation of endopeptidase activity
post-translational protein modification
cellular protein metabolic process

Molecular Function

endopeptidase inhibitor activity

Cellular Component

extracellular region
endoplasmic reticulum lumen
platelet dense granule lumen
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000168148
Coding exons: 7
Length: 26456
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125747
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.389	136	124	1.10	0.00000691	1398
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Could coordinate an aspect of bone turnover. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.814
RVIS EVS: -0.32
RVIS percentile EVS: 31.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00449

Gene Damage Prediction

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