SCUBE3

signal peptide, CUB domain and EGF like domain containing 3

Basic information

Region (hg38): 6:35213956-35253079

Previous symbols: [ "CEGF3" ]

Links

ENSG00000146197 ∙ NCBI:222663 ∙ OMIM:614708 ∙ HGNC:13655 ∙ Uniprot:Q8IX30 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2 (Strong), mode of inheritance: AR
• short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2 (Moderate), mode of inheritance: AR
• short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies	AR	Cardiovascular	Among other features, the condition can involve arrhythmias, and awareness can allow early diagnosis and management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dental; Musculoskeletal; Neurologic	33308444

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCUBE3 gene.

• Inborn_genetic_diseases (109 variants)
• not_provided (15 variants)
• Short_stature,_facial_dysmorphism,_and_skeletal_anomalies_with_or_without_cardiac_anomalies_2 (15 variants)
• Short_stature (8 variants)
• Abnormal_facial_shape (8 variants)
• Abnormality_of_the_dentition (8 variants)
• Abnormality_of_the_skeletal_system (8 variants)
• Prostate_cancer (1 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCUBE3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000152753.4. 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			1
missense	2	1	120	3	2	128
nonsense	2	2				4
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)	4	1				5
Total	8	4	122	3	2

Highest pathogenic variant AF is 0.000025993711

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCUBE3	protein_coding	protein_coding	ENST00000274938	22	38667

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000614	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.70	425	613	0.693	0.0000371	6552
Missense in Polyphen		147	249.98	0.58804		2711
Synonymous	2.27	191	235	0.812	0.0000145	1895
Loss of Function	5.80	7	52.2	0.134	0.00000289	593

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000246	0.000242
Ashkenazi Jewish	0.000398	0.000397
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000441	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to TGFBR2 and activates TGFB signaling. In lung cancer cells, could serve as an endogenous autocrine and paracrine ligand of TGFBR2, which could regulate TGFBR2 signaling and hence modulate epithelial-mesenchymal transition and cancer progression. {ECO:0000269|PubMed:21441952}.
• Pathway: Extracellular matrix organization;Degradation of the extracellular matrix (Consensus)

Recessive Scores

• pRec: 0.0910

Intolerance Scores

• loftool: 0.0393
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.66

Haploinsufficiency Scores

• pHI: 0.246
• hipred: Y
• hipred_score: 0.765
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.357

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Scube3
• Phenotype: limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; skeleton phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: extracellular matrix disassembly;positive regulation of smoothened signaling pathway;protein homooligomerization;protein heterooligomerization
• Cellular component: extracellular space;plasma membrane;cell surface
• Molecular function: calcium ion binding;protein binding