SMOC1

protein-coding

SPARC related modular calcium binding 1, the group of SPARC family

Gene summary

This gene encodes a multi-domain secreted protein that may have a critical role in ocular and limb development. Mutations in this gene are associated with microphthalmia and limb anomalies. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

MANE transcript

NM_001034852.3

Inheritance

ClinVar variants

P:22U:77B:44

Top phenotype

Microphthalmia with limb anomalies

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr14:69,854,131-70,032,366

External References & Databases

Ensembl (ENSG00000198732)

Transcript & Mutation Effects

hg38 • Region Span ~178.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microphthalmia with limb anomaliesDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008800

Submitter: G2P

microphthalmia with limb anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008800

Submitter: Labcorp Genetics (formerly Invitae)

microphthalmia with limb anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008800

Submitter: PanelApp Australia

microphthalmia with limb anomaliesSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008800

Submitter: Orphanet

Clinical Genomic Database (CGD)

Microphthalmia with limb anomaliesAR

Manifestation: Musculoskeletal; Ophthalmologic

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: 21194678; 21194680

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SMOC1 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 91

Inborn genetic diseasesTotal: 68

Microphthalmia with limb anomaliesTotal: 16

SMOC1-related disorderTotal: 13

not specifiedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001034852.3. 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			1 clinvar	35 clinvar	1 clinvar	37
missense	2 clinvar	3 clinvar	75 clinvar	7 clinvar	1 clinvar	88
nonsense	6 clinvar	2 clinvar	1 clinvar			9
start loss						0
frameshift	2 clinvar	2 clinvar				4
splice donor/acceptor (+/-2bp)	3 clinvar	2 clinvar				5
Total	13	9	77	42	2	143

Highest pathogenic variant AF is 0.000078101366

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001034852.3	RefSeq	NP_001030024.1	12	MANE Select
ENST00000361956.8	Ensembl	ENSP00000355110.4	12	MANE Select
NM_001425244.1	RefSeq	NP_001412173.1	12	Standard
NM_001425245.1	RefSeq	NP_001412174.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
smoc1	Danio rerio	Structure: optic fissure Quality: open abnormal

Gene / Model

Organism

Observed Phenotype

smoc1

Danio rerio

Structure: optic fissure

Quality: open

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

eye development
cell differentiation
regulation of osteoblast differentiation
limb development

Molecular Function

calcium ion binding
protein binding
extracellular matrix binding

Cellular Component

basement membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361956
Coding exons: 12
Length: 178236
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125744
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.743	214	247	0.867	0.0000151	2822
Missense (PolyPhen)		74	111.81	0.66185		1284
Synonymous	1.55	79	98.6	0.801	0.00000616	845
Loss of Function	3.08	8	24.4	0.328	0.00000130	281

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00049	0.00049	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays essential roles in both eye and limb development. Probable regulator of osteoblast differentiation. {ECO:0000269|PubMed:20359165, ECO:0000269|PubMed:21194678, ECO:0000269|PubMed:21194680}.;
Disease: DISEASE: Ophthalmoacromelic syndrome (OAS) [MIM:206920]: A rare disorder presenting with ocular anomalies, ranging from mild microphthalmia to true anophthalmia, and limb anomalies. Limb malformations include fused 4th and 5th metacarpals and short 5th finger in hands, and oligodactyly in foot (four toes). Most patients have bilateral anophthalmia/ microphthalmia, but unilateral abnormality is also noted. Other malformations are rare, but venous or vertebral anomaly was recognized each in single cases. {ECO:0000269|PubMed:21194678, ECO:0000269|PubMed:21194680, ECO:0000269|PubMed:21750680, ECO:0000269|PubMed:23646827}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.131

Intolerance Scores

LoFtool: 0.702
RVIS EVS: 0.02
RVIS percentile EVS: 55.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0867

Gene Damage Prediction

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