SMOC2

protein-coding

SPARC related modular calcium binding 2, the group of SPARC family

Gene summary

This gene encodes a member of the SPARC family (secreted protein acidic and rich in cysteine/osteonectin/BM-40), which are highly expressed during embryogenesis and wound healing. The gene product is a matricellular protein which promotes matrix assembly and can stimulate endothelial cell proliferation and migration, as well as angiogenic activity. Associated with pulmonary function, this secretory gene product contains a Kazal domain, two thymoglobulin type-1 domains, and two EF-hand calcium-binding domains. The encoded protein may serve as a target for controlling angiogenesis in tumor growth and myocardial ischemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

MANE transcript

NM_001166412.2

Inheritance

ClinVar variants

P:4U:108B:30

Top phenotype

Dentin dysplasia, type I

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr6:168,441,151-168,673,445

External References & Databases

Ensembl (ENSG00000112562)

Transcript & Mutation Effects

hg38 • Region Span ~232.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

dentin dysplasia type ISTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007436

Submitter: Labcorp Genetics (formerly Invitae)

dentin dysplasia type ILIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0007436

Submitter: Ambry Genetics

dentin dysplasia type ISTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007436

Submitter: G2P

atypical dentin dysplasia due to SMOC2 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0017819

Submitter: PanelApp Australia

atypical dentin dysplasia due to SMOC2 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017819

Submitter: Orphanet

Clinical Genomic Database (CGD)

Dentin dysplasia, type IAR

Manifestation: Dental

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 22152679; 23317772

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SMOC2 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 102

not providedTotal: 57

SMOC2-related disorderTotal: 8

Dentin dysplasia type ITotal: 5

SchizophreniaTotal: 1

Dentin dysplasia, type IATotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001166412.2. 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				17 clinvar	8 clinvar	25
missense			104 clinvar	4 clinvar	1 clinvar	109
nonsense	2 clinvar		1 clinvar			3
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)	1 clinvar		3 clinvar			4
Total	3	1	108	21	9	142

Highest pathogenic variant AF is 0.000008208574

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001166412.2	RefSeq	NP_001159884.1	13	MANE Select
ENST00000356284.7	Ensembl	ENSP00000348630.3	13	MANE Select
NM_022138.3	RefSeq	NP_071421.1	13	Standard
ENST00000354536.10	Ensembl	ENSP00000346537.5	13	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
smoc2	Danio rerio	Structure: neutrophil Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

smoc2

Danio rerio

Structure: neutrophil

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gastric Cancer Network 1

Biological Process

positive regulation of endothelial cell migration
positive regulation of cell-substrate adhesion
extracellular matrix organization
positive regulation of vascular wound healing
positive regulation of fibroblast growth factor receptor signaling pathway

Molecular Function

calcium ion binding
heparin binding

Cellular Component

basement membrane
interstitial matrix
extracellular space
cell periphery

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354536
Coding exons: 13
Length: 232154
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125748
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.642	254	284	0.893	0.0000186	2956
Missense (PolyPhen)		72	97.044	0.74193		900
Synonymous	0.0349	122	122	0.996	0.00000912	859
Loss of Function	3.00	9	25.3	0.356	0.00000107	318

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes matrix assembly and cell adhesiveness (By similarity). Can stimulate endothelial cell proliferation, migration, as well as angiogenesis. {ECO:0000250, ECO:0000269|PubMed:16774925}.;
Disease: DISEASE: Dentin dysplasia 1 (DTDP1) [MIM:125400]: A dental defect in which both primary and secondary dentitions are affected. The clinical crowns of both permanent and deciduous teeth are of normal shape, form and color in most cases, although they may be slightly opalescent and blue or brown. Teeth may be very mobile and exfoliate spontaneously because of inadequate root formation. On radiographs, the roots are short and may be more pointed than normal. Pulp chambers are usually absent except for a chevron- shaped remnant in the crown. Root canals are usually absent. {ECO:0000269|PubMed:22152679}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.696
RVIS EVS: -0.53
RVIS percentile EVS: 20.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.793

Gene Damage Prediction

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