SMOC1

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

Basic information

Region (hg38): 14:69854131-70032366

Links

ENSG00000198732 ∙ NCBI:64093 ∙ OMIM:608488 ∙ HGNC:20318 ∙ Uniprot:Q9H4F8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microphthalmia with limb anomalies (Strong), mode of inheritance: AR
• microphthalmia with limb anomalies (Supportive), mode of inheritance: AR
• microphthalmia with limb anomalies (Strong), mode of inheritance: AR
• microphthalmia with limb anomalies (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia with limb anomalies	AR	General	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	Musculoskeletal; Ophthalmologic	21194678; 21194680

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMOC1 gene.

• not_provided (87 variants)
• Inborn_genetic_diseases (68 variants)
• Microphthalmia_with_limb_anomalies (16 variants)
• SMOC1-related_disorder (8 variants)
• not_specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMOC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001034852.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	33	2	36
missense	2	3	74	6	2	87
nonsense	6		1			7
start loss						0
frameshift	2	1				3
splice donor/acceptor (+/-2bp)	3	1				4
Total	13	5	76	39	4

Highest pathogenic variant AF is 0.000078101366

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMOC1	protein_coding	protein_coding	ENST00000361956	12	178236

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125715	0	29	125744	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.743	214	247	0.867	0.0000151	2822
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000553	0.000553
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000618	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

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_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0867

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: smoc1
• Affected structure: optic fissure
• Phenotype tag: abnormal
• Phenotype quality: open

Gene ontology

• Biological process: eye development;cell differentiation;regulation of osteoblast differentiation;limb development
• Cellular component: basement membrane
• Molecular function: calcium ion binding;protein binding;extracellular matrix binding