NSMCE3

NSE3 homolog, SMC5-SMC6 complex component, the group of SMC5-6 protein complex|MAGE family

Basic information

Region (hg38): 15:29264988-29269822

Previous symbols: [ "NDNL2" ]

Links

ENSG00000185115 ∙ NCBI:56160 ∙ OMIM:608243 ∙ HGNC:7677 ∙ Uniprot:Q96MG7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lung disease, immunodeficiency, and chromosome breakage syndrome	AR	Allergy/Immunology/Infectious	Individuals have been described with severe and early-onset infections, and early awareness may allow preventive measures and early and aggressive treatment of infections	Allergy/Immunology/Infectious; Craniofacial; Pulmonary	27427983

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NSMCE3 gene.

• Lung disease, immunodeficiency, and chromosome breakage syndrome; (2 variants)
• Lung damage, immunodeficiency and chromosome breakage syndrome (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NSMCE3 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				93	2	95
missense	2		68	4	4	78
nonsense			2			2
start loss						0
frameshift			2			2
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	2	0	74	97	6

Highest pathogenic variant AF is 0.0000526

Variants in NSMCE3

This is a list of pathogenic ClinVar variants found in the NSMCE3 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-29268804-G-A			Uncertain significance (Jul 12, 2022)
15-29268808-G-A			Uncertain significance (Aug 10, 2022)
15-29268817-G-A			Uncertain significance (Mar 05, 2022)
15-29268818-C-T			Likely benign (Jun 06, 2023)
15-29268825-C-T			Uncertain significance (Dec 13, 2021)
15-29268829-C-T			Uncertain significance (Aug 19, 2022)
15-29268830-C-T			Likely benign (Dec 13, 2023)
15-29268835-TCTC-T			Uncertain significance (Jul 18, 2022)
15-29268845-T-C			Likely benign (Nov 19, 2023)
15-29268848-CAAAGCC-ATCTTAAT			Uncertain significance (Aug 09, 2022)
15-29268854-C-T			Likely benign (Aug 06, 2023)
15-29268856-C-G			Uncertain significance (Jun 25, 2022)
15-29268860-G-A			Likely benign (Dec 05, 2023)
15-29268861-T-C			Uncertain significance (May 25, 2022)
15-29268866-C-G			Likely benign (Jan 04, 2024)
15-29268867-G-A			Uncertain significance (Dec 12, 2021)
15-29268868-C-A			Uncertain significance (Jan 07, 2022)
15-29268869-T-C			Likely benign (Feb 14, 2023)
15-29268880-T-C			Uncertain significance (Jun 20, 2022)
15-29268892-T-C			Uncertain significance (Jul 11, 2022)
15-29268896-G-C			Likely benign (May 01, 2023)
15-29268916-G-A		Lung damage, immunodeficiency and chromosome breakage syndrome • Lung disease, immunodeficiency, and chromosome breakage syndrome;	Pathogenic (Apr 11, 2024)
15-29268926-C-T			Likely benign (Feb 19, 2023)
15-29268942-T-A			Benign (Jan 31, 2024)
15-29268946-T-A			Uncertain significance (Dec 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NSMCE3	protein_coding	protein_coding	ENST00000332303	1	1681

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0562	0.873	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.334	174	162	1.07	0.00000741	1946
Missense in Polyphen		30	44.158	0.67938		572
Synonymous	-2.32	97	72.0	1.35	0.00000336	622
Loss of Function	1.51	3	7.45	0.403	3.30e-7	88

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination (PubMed:20864041, PubMed:27427983). 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). In vitro enhances ubiquitin ligase activity of NSMCE1. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex (PubMed:20864041). May be a growth suppressor that facilitates the entry of the cell into cell cycle arrest (By similarity). {ECO:0000250|UniProtKB:Q9CPR8, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:27427983}.
• Pathway: SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;SUMOylation;p75(NTR)-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• rvis_EVS: 0.51
• rvis_percentile_EVS: 80.01

Haploinsufficiency Scores

• pHI: 0.0975
• hipred: Y
• hipred_score: 0.552
• ghis: 0.547

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Nsmce3

Gene ontology

• Biological process: DNA repair;DNA recombination;positive regulation of protein ubiquitination;cellular response to UV;regulation of growth;cellular response to radiation;cellular response to hydroxyurea
• Cellular component: chromosome, telomeric region;nucleoplasm;cytoplasm;Smc5-Smc6 complex
• Molecular function: protein binding;protein dimerization activity