SMC5

structural maintenance of chromosomes 5, the group of Structural maintenance of chromosomes proteins|SMC5-6 protein complex

Basic information

Region (hg38): 9:70258977-70354873

Previous symbols: [ "SMC5L1" ]

Links

ENSG00000198887 ∙ NCBI:23137 ∙ OMIM:609386 ∙ HGNC:20465 ∙ Uniprot:Q8IY18 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Atelis syndrome 2 (Moderate), mode of inheritance: AR
• Atelis syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atelis syndrome 2	AR	Allergy/Immunology/Infectious; Cardiovascular; Oncologic	Individuals have been described with congenital heart anomalies, and awareness may enable prompt recognition and management; The condition may involve increased risk of hematologic malignancy, and awareness may allow prompt diagnosis and management	Cardiovascular; Craniofacial; Dental; Hematologic; Neurologic; Oncologic; Ophthalmologic	36333305

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMC5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMC5 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					3	3
missense			47	3	1	51
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	47	3	4

Variants in SMC5

This is a list of pathogenic ClinVar variants found in the SMC5 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-70259107-C-T		Inborn genetic diseases	Uncertain significance (Nov 07, 2023)
9-70259136-C-G		not specified	Uncertain significance (Jul 07, 2022)
9-70259143-G-C		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
9-70259152-C-T		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
9-70259215-G-C		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
9-70264335-C-T		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
9-70264353-G-A		Inborn genetic diseases	Likely benign (Dec 19, 2022)
9-70264388-G-A			Benign (Dec 31, 2019)
9-70277379-C-G		Inborn genetic diseases	Uncertain significance (Oct 03, 2023)
9-70278576-A-G		Inborn genetic diseases	Likely benign (Nov 14, 2023)
9-70280799-T-C		Inborn genetic diseases	Uncertain significance (Apr 04, 2023)
9-70280811-A-G		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
9-70280817-A-G		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
9-70280897-G-T		Inborn genetic diseases	Uncertain significance (Jul 07, 2022)
9-70282476-G-C		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
9-70282519-T-C		Inborn genetic diseases	Uncertain significance (Feb 13, 2024)
9-70282525-G-A		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
9-70282551-C-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2022)
9-70282579-A-G		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
9-70286269-C-A		Inborn genetic diseases	Uncertain significance (Mar 25, 2024)
9-70297993-G-A		Inborn genetic diseases	Uncertain significance (Oct 30, 2023)
9-70298021-AGAG-A		Atelis syndrome 2	Pathogenic (Feb 16, 2023)
9-70298071-C-G		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
9-70298090-G-A		Inborn genetic diseases	Uncertain significance (Jun 18, 2024)
9-70298091-C-T		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMC5	protein_coding	protein_coding	ENST00000361138	25	95868

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000313	1.00	125694	0	54	125748	0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.08	487	559	0.871	0.0000290	7267
Missense in Polyphen		129	209.31	0.61632		2720
Synonymous	0.247	186	190	0.977	0.00000953	1921
Loss of Function	4.92	22	64.7	0.340	0.00000361	823

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000395	0.000394
Ashkenazi Jewish	0.000114	0.0000992
East Asian	0.000399	0.000381
Finnish	0.000325	0.000323
European (Non-Finnish)	0.000218	0.000211
Middle Eastern	0.000399	0.000381
South Asian	0.000143	0.000131
Other	0.000360	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core component of the SMC5-SMC6 complex, a complex involved in repair of 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. Required for sister chromatid cohesion during prometaphase and mitotic progression; the function seems to be independent of SMC6. 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:19502785, 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: 0.116

Intolerance Scores

• loftool: 0.689
• rvis_EVS: -0.28
• rvis_percentile_EVS: 33.53

Haploinsufficiency Scores

• pHI: 0.355
• hipred: Y
• hipred_score: 0.579
• ghis: 0.601

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.656

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smc5
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); cellular phenotype

Gene ontology

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