SPOCK3

protein-coding

SPARC (osteonectin), cwcv and kazal like domains proteoglycan 3, the group of SPARC family

Gene summary

This gene encodes a member of a novel family of calcium-binding proteoglycan proteins that contain thyroglobulin type-1 and Kazal-like domains. The encoded protein and may play a role in adult T-cell leukemia by inhibiting the activity of membrane-type matrix metalloproteinases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

MANE transcript

NM_001040159.2

Inheritance

—

ClinVar variants

U:55B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr4:166,733,384-167,234,796

External References & Databases

Ensembl (ENSG00000196104)

Transcript & Mutation Effects

hg38 • Region Span ~501.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPOCK3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 55

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001040159.2. 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	1 clinvar	3
missense			54 clinvar		2 clinvar	56
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	55	2	3	60

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001040159.2	RefSeq	NP_001035249.1	10	MANE Select
ENST00000357545.9	Ensembl	ENSP00000350153.4	10	MANE Select
NM_001204352.2	RefSeq	NP_001191281.1	10	Standard
NM_001204353.1	RefSeq	NP_001191282.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Extracellular matrix organization
Activation of Matrix Metalloproteinases
Degradation of the extracellular matrix

Biological Process

negative regulation of endopeptidase activity
peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan
negative regulation of cell motility

Molecular Function

calcium ion binding
collagen binding
glycosaminoglycan binding
metalloendopeptidase inhibitor activity
extracellular matrix binding

Cellular Component

extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357154
Coding exons: 11
Length: 501413
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.390	219	236	0.929	0.0000111	2914
Missense (PolyPhen)		72	78.665	0.91527		985
Synonymous	-1.65	104	84.7	1.23	0.00000414	739
Loss of Function	3.20	8	25.4	0.315	0.00000109	305

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000035	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May participate in diverse steps of neurogenesis. Inhibits the processing of pro-matrix metalloproteinase 2 (MMP-2) by MT1-MMP and MT3-MMP. May interfere with tumor invasion.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.623
RVIS EVS: 0.04
RVIS percentile EVS: 57.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.687

Gene Damage Prediction

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