NSMCE3

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

Basic information

Region (hg38): 15:29264989-29269822

Previous symbols: [ "NDNL2" ]

Links

ENSG00000185115NCBI:56160OMIM:608243HGNC:7677Uniprot:Q96MG7AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Lung disease, immunodeficiency, and chromosome breakage syndromeARAllergy/Immunology/InfectiousIndividuals have been described with severe and early-onset infections, and early awareness may allow preventive measures and early and aggressive treatment of infectionsAllergy/Immunology/Infectious; Craniofacial; Pulmonary27427983

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
clinvar
2
clinvar
95
missense
2
clinvar
68
clinvar
4
clinvar
4
clinvar
78
nonsense
2
clinvar
2
start loss
0
frameshift
2
clinvar
2
inframe indel
2
clinvar
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)1462904
15-29268808-G-A Uncertain significance (Aug 10, 2022)1376218
15-29268817-G-A Uncertain significance (Mar 05, 2022)2138579
15-29268818-C-T Likely benign (Jun 06, 2023)2893039
15-29268825-C-T Uncertain significance (Dec 13, 2021)2041856
15-29268829-C-T Uncertain significance (Aug 19, 2022)1004005
15-29268830-C-T Likely benign (Dec 13, 2023)2993197
15-29268835-TCTC-T Uncertain significance (Jul 18, 2022)1019113
15-29268845-T-C Likely benign (Nov 19, 2023)1138252
15-29268848-CAAAGCC-ATCTTAAT Uncertain significance (Aug 09, 2022)1962918
15-29268854-C-T Likely benign (Aug 06, 2023)1962919
15-29268856-C-G Uncertain significance (Jun 25, 2022)2007850
15-29268860-G-A Likely benign (Dec 05, 2023)1644102
15-29268861-T-C Uncertain significance (May 25, 2022)1998400
15-29268866-C-G Likely benign (Jan 04, 2024)1635042
15-29268867-G-A Uncertain significance (Dec 12, 2021)1948438
15-29268868-C-A Uncertain significance (Jan 07, 2022)2077518
15-29268869-T-C Likely benign (Feb 14, 2023)2985204
15-29268880-T-C Uncertain significance (Jun 20, 2022)1421457
15-29268892-T-C Uncertain significance (Jul 11, 2022)2016181
15-29268896-G-C Likely benign (May 01, 2023)2781899
15-29268916-G-A Lung damage, immunodeficiency and chromosome breakage syndrome • Lung disease, immunodeficiency, and chromosome breakage syndrome; Pathogenic (Apr 11, 2024)267795
15-29268926-C-T Likely benign (Feb 19, 2023)2969810
15-29268942-T-A Benign (Jan 31, 2024)710048
15-29268946-T-A Uncertain significance (Dec 18, 2023)1384651

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NSMCE3protein_codingprotein_codingENST00000332303 11681
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.05620.87300000.00
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.3341741621.070.000007411946
Missense in Polyphen3044.1580.67938572
Synonymous-2.329772.01.350.00000336622
Loss of Function1.5137.450.4033.30e-788

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

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

loftool
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_CRISPR
essential_gene_CRISPR2
essential_gene_gene_trap
N
gene_indispensability_pred
gene_indispensability_score

Mouse Genome Informatics

Gene name
Nsmce3
Phenotype

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