SMC6

structural maintenance of chromosomes 6, the group of SMC5-6 protein complex|Structural maintenance of chromosomes proteins

Basic information

Region (hg38): 2:17663811-17800242

Previous symbols: [ "SMC6L1" ]

Links

ENSG00000163029 ∙ NCBI:79677 ∙ OMIM:609387 ∙ HGNC:20466 ∙ Uniprot:Q96SB8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMC6 gene.

• Inborn genetic diseases (17 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMC6 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					1	1
missense			17			17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	0	1

Variants in SMC6

This is a list of pathogenic ClinVar variants found in the SMC6 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-17665512-T-C		not specified	Uncertain significance (Jun 10, 2022)
2-17665587-C-T		not specified	Uncertain significance (Jan 30, 2024)
2-17665599-C-G		not specified	Uncertain significance (May 03, 2023)
2-17678893-T-C		not specified	Uncertain significance (May 03, 2023)
2-17678933-C-G		not specified	Uncertain significance (Sep 01, 2021)
2-17695260-C-T		not specified	Uncertain significance (Jun 13, 2023)
2-17695261-G-A		not specified	Uncertain significance (Feb 27, 2023)
2-17695267-G-A		not specified	Uncertain significance (Jan 23, 2023)
2-17696386-T-C		not specified	Uncertain significance (Feb 12, 2024)
2-17701890-A-T		not specified	Likely benign (Feb 27, 2024)
2-17703239-T-C		not specified	Uncertain significance (Dec 20, 2023)
2-17703263-G-A		not specified	Likely benign (Jan 29, 2024)
2-17707318-G-A		not specified	Uncertain significance (Mar 01, 2024)
2-17708651-C-T			Benign (Aug 02, 2017)
2-17714888-C-T		not specified	Uncertain significance (Apr 12, 2022)
2-17716137-C-T		not specified	Uncertain significance (Sep 01, 2021)
2-17716140-T-G		not specified	Uncertain significance (Jan 16, 2024)
2-17716146-C-T		not specified	Uncertain significance (Oct 25, 2023)
2-17716229-T-G		not specified	Uncertain significance (Feb 23, 2023)
2-17716775-T-C		not specified	Uncertain significance (Dec 01, 2023)
2-17716777-G-T		not specified	Uncertain significance (Jul 12, 2022)
2-17716804-T-C		not specified	Uncertain significance (Nov 30, 2022)
2-17716822-T-C		not specified	Uncertain significance (Jul 13, 2021)
2-17718176-T-G		not specified	Uncertain significance (May 24, 2023)
2-17718217-G-C		not specified	Uncertain significance (Oct 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMC6	protein_coding	protein_coding	ENST00000448223	26	136431

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000266	1.00	125689	0	45	125734	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.21	403	549	0.734	0.0000277	7269
Missense in Polyphen		78	152.93	0.51005		2150
Synonymous	-0.738	194	181	1.07	0.00000891	1893
Loss of Function	4.88	22	64.2	0.343	0.00000376	804

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000298	0.000298
Ashkenazi Jewish	0.0000998	0.0000992
East Asian	0.0000546	0.0000544
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000180	0.000176
Middle Eastern	0.0000546	0.0000544
South Asian	0.000370	0.000359
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core component of the SMC5-SMC6 complex, a complex involved in DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs). Required for recruitment of telomeres to PML nuclear bodies. SMC5-SMC6 complex may prevent transcription of episomal DNA, such as circular viral DNA genome (PubMed:26983541). {ECO:0000269|PubMed:16810316, ECO:0000269|PubMed:17589526, ECO:0000269|PubMed:26983541}.
• Pathway: SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;SUMOylation (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.830
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.94

Haploinsufficiency Scores

• pHI: 0.894
• hipred: Y
• hipred_score: 0.706
• ghis: 0.631

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.779

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smc6
• Phenotype: immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; reproductive 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); 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: telomere maintenance via recombination;double-strand break repair via homologous recombination;cellular response to DNA damage stimulus;positive regulation of chromosome segregation;cellular senescence
• Cellular component: chromosome, telomeric region;sex chromosome;nucleus;nucleoplasm;PML body;nuclear speck;Smc5-Smc6 complex;interchromatin granule;site of double-strand break
• Molecular function: protein binding;ATP binding;ubiquitin protein ligase binding