SMC3

structural maintenance of chromosomes 3, the group of Proteoglycans|Cohesin complex|Structural maintenance of chromosomes proteins

Basic information

Region (hg38): 10:110567683-110606048

Previous symbols: [ "CSPG6" ]

Links

ENSG00000108055 ∙ NCBI:9126 ∙ OMIM:606062 ∙ HGNC:2468 ∙ Uniprot:Q9UQE7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Cornelia de Lange syndrome 3 (Definitive), mode of inheritance: AD
• Cornelia de Lange syndrome 3 (Strong), mode of inheritance: AD
• Cornelia de Lange syndrome (Supportive), mode of inheritance: AD
• Cornelia de Lange syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cornelia de Lange syndrome 3 with or without midline brain defects	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	17273969; 24403048; 31334757

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMC3 gene.

• Cornelia de Lange syndrome 3 (244 variants)
• not provided (190 variants)
• Inborn genetic diseases (60 variants)
• not specified (35 variants)
• De Lange syndrome (8 variants)
• SMC3-related condition (8 variants)
• Intellectual disability (2 variants)
• See cases (2 variants)
• Neurodevelopmental disorder (1 variants)
• Autism spectrum disorder (1 variants)
• Cornelia de Lange syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMC3 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	56	4	67
missense	4	33	106	5		148
nonsense	1		8			9
start loss						0
frameshift	1		4			5
inframe indel	1	5	2			8
splice donor/acceptor (+/-2bp)		1			1	2
splice region			11	15	4	30
non coding			19	66	75	160
Total	7	39	146	127	80

Highest pathogenic variant AF is 0.00000657

Variants in SMC3

This is a list of pathogenic ClinVar variants found in the SMC3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-110567687-G-A		De Lange syndrome	Likely benign (Jun 14, 2016)
10-110567702-T-C		Cornelia de Lange syndrome 3	Uncertain significance (Jan 13, 2018)
10-110567718-C-A		Cornelia de Lange syndrome 3	Benign/Likely benign (Dec 09, 2018)
10-110567725-G-T		Cornelia de Lange syndrome 3	Benign (Jan 13, 2018)
10-110567727-G-A		Cornelia de Lange syndrome 3	Uncertain significance (Jan 13, 2018)
10-110567743-C-A		Cornelia de Lange syndrome 3	Likely benign (Jan 13, 2018)
10-110567752-T-A		Cornelia de Lange syndrome 3	Uncertain significance (Jan 13, 2018)
10-110567823-A-G		Cornelia de Lange syndrome 3	Uncertain significance (Aug 12, 2019)
10-110567824-T-G		Cornelia de Lange syndrome 3	Uncertain significance (Jul 17, 2023)
10-110567835-AGGCCTTCG-A		Cornelia de Lange syndrome 3	Uncertain significance (Jul 17, 2023)
10-110567839-C-G		Cornelia de Lange syndrome 3	Likely benign (Nov 04, 2022)
10-110567842-C-T		Cornelia de Lange syndrome 3	Likely benign (Jul 30, 2022)
10-110567843-G-A		Cornelia de Lange syndrome 3	Likely benign (Jul 19, 2022)
10-110567920-C-CA			Benign (Jun 16, 2018)
10-110567965-G-A			Likely benign (Sep 26, 2018)
10-110568767-CT-C			Likely benign (Dec 19, 2019)
10-110568767-C-CT			Benign (Aug 27, 2019)
10-110568767-C-CTTT			Benign (May 25, 2021)
10-110568859-AAAAC-A			Benign (Dec 05, 2020)
10-110568892-A-AT			Benign (Dec 18, 2018)
10-110568922-G-A		Cornelia de Lange syndrome 3	Likely benign (Oct 07, 2023)
10-110568955-T-C		Cornelia de Lange syndrome 3	Likely benign (Jul 28, 2022)
10-110568991-C-T		Inborn genetic diseases • Cornelia de Lange syndrome 3	Likely benign (Dec 11, 2023)
10-110569080-C-G			Benign (Jun 16, 2018)
10-110569234-CTAGG-C			Benign (Nov 22, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMC3	protein_coding	protein_coding	ENST00000361804	29	36946

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.19e-13	125731	0	8	125739	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	6.40	178	630	0.283	0.0000325	8109
Missense in Polyphen		21	182.52	0.11506		2197
Synonymous	-0.648	215	203	1.06	0.00000980	2091
Loss of Function	8.26	0	79.5	0.00	0.00000454	937

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000441	0.0000440
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex plays also an important role in spindle pole assembly during mitosis and in chromosomes movement. {ECO:0000269|PubMed:11076961, ECO:0000269|PubMed:19907496}.
• Disease: DISEASE: Cornelia de Lange syndrome 3 (CDLS3) [MIM:610759]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. Cornelia de Lange syndrome type 3 is a mild form with absence of major structural anomalies. The phenotype in some instances approaches that of apparently non- syndromic mental retardation. {ECO:0000269|PubMed:17273969, ECO:0000269|PubMed:18996922}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Retinoblastoma (RB) in Cancer;MECP2 and Associated Rett Syndrome;Prion disease pathway;Regulation of sister chromatid separation at the metaphase-anaphase transition;Signal Transduction;SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Reproduction;SUMOylation;Establishment of Sister Chromatid Cohesion;S Phase;Meiotic synapsis;Meiosis;Integrin;Signaling by Nuclear Receptors;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;Cohesin Loading onto Chromatin;Mitotic Telophase/Cytokinesis;M Phase;Estrogen-dependent gene expression;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;ESR-mediated signaling;ATM pathway (Consensus)

Recessive Scores

• pRec: 0.0988

Intolerance Scores

• loftool: 0.0496
• rvis_EVS: -0.89
• rvis_percentile_EVS: 10.3

Haploinsufficiency Scores

• pHI: 0.977
• hipred: Y
• hipred_score: 0.783
• ghis: 0.705

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smc3
• Phenotype: craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); pigmentation phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: smc3
• Affected structure: cell
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: mitotic cell cycle;regulation of DNA replication;DNA repair;sister chromatid cohesion;stem cell population maintenance;negative regulation of DNA endoreduplication;positive regulation by host of viral release from host cell;cell division;meiotic cell cycle;interaction with symbiont;regulation of mitotic spindle assembly
• Cellular component: chromosome, centromeric region;chromatin;lateral element;basement membrane;nucleus;nucleoplasm;chromosome;cytosol;cohesin complex;nuclear matrix;meiotic cohesin complex;nuclear meiotic cohesin complex;mitotic spindle pole
• Molecular function: chromatin binding;microtubule motor activity;protein binding;ATP binding;mediator complex binding;protein heterodimerization activity;beta-tubulin binding;dynein complex binding