NSMCE1

NSE1 homolog, SMC5-SMC6 complex component, the group of SMC5-6 protein complex|Ring finger proteins

Basic information

Region (hg38): 16:27224994-27268772

Links

ENSG00000169189 ∙ NCBI:197370 ∙ OMIM:617263 ∙ HGNC:29897 ∙ Uniprot:Q8WV22 ∙ 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 NSMCE1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NSMCE1 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						0
missense			18	2		20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	2	0

Variants in NSMCE1

This is a list of pathogenic ClinVar variants found in the NSMCE1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-27225173-C-T		not specified	Uncertain significance (Aug 27, 2024)
16-27225174-G-C		not specified	Uncertain significance (Dec 19, 2022)
16-27225191-G-A		not specified	Uncertain significance (May 20, 2024)
16-27225755-C-T		not specified	Uncertain significance (Dec 28, 2022)
16-27225792-A-G		not specified	Uncertain significance (Jan 16, 2025)
16-27225817-C-G		not specified	Uncertain significance (Nov 10, 2022)
16-27226760-G-A		not specified	Uncertain significance (Jun 18, 2021)
16-27226772-G-A		not specified	Uncertain significance (Dec 06, 2021)
16-27226773-T-C		not specified	Uncertain significance (Jun 05, 2023)
16-27226778-C-T		not specified	Uncertain significance (Dec 16, 2022)
16-27226808-C-T		not specified	Uncertain significance (Feb 26, 2024)
16-27226812-C-T		not specified	Likely benign (Dec 02, 2024)
16-27226834-C-G		not specified	Uncertain significance (Feb 12, 2025)
16-27233042-G-C		not specified	Uncertain significance (May 17, 2023)
16-27233114-C-A		not specified	Uncertain significance (Jan 17, 2025)
16-27234244-T-C		not specified	Likely benign (Jan 31, 2023)
16-27234255-G-A		not specified	Uncertain significance (Oct 07, 2024)
16-27235209-G-A		not specified	Uncertain significance (Jun 12, 2023)
16-27257468-G-A		not specified	Uncertain significance (Nov 11, 2024)
16-27257477-C-T		not specified	Uncertain significance (Jan 24, 2025)
16-27257486-C-T		not specified	Uncertain significance (Nov 11, 2024)
16-27257543-C-T		not specified	Uncertain significance (Oct 12, 2021)
16-27257555-T-C		not specified	Uncertain significance (Oct 10, 2023)
16-27257563-C-T		not specified	Uncertain significance (Aug 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NSMCE1	protein_coding	protein_coding	ENST00000361439	7	43804

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000218	0.741	124726	0	82	124808	0.000329

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.558	141	161	0.876	0.00000973	1762
Missense in Polyphen		48	65.668	0.73095		760
Synonymous	0.0236	69	69.3	0.996	0.00000483	472
Loss of Function	1.10	9	13.3	0.675	6.52e-7	161

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000854	0.000854
Ashkenazi Jewish	0.000199	0.000199
East Asian	0.0000557	0.0000556
Finnish	0.00121	0.00121
European (Non-Finnish)	0.000177	0.000177
Middle Eastern	0.0000557	0.0000556
South Asian	0.0000980	0.0000980
Other	0.000496	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: RING-type zinc finger-containing E3 ubiquitin ligase that assembles with melanoma antigen protein (MAGE) to catalyze the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. Within MAGE-RING ubiquitin ligase complex, MAGE stimulates and specifies ubiquitin ligase activity likely through recruitment and/or stabilization of the E2 ubiquitin-conjugating enzyme at the E3:substrate complex. Involved in maintenance of genome integrity, DNA damage response and DNA repair (PubMed:29225034, PubMed:20864041). NSMCE3/MAGEG1 and NSMCE1 ubiquitin ligase are components of SMC5-SMC6 complex and may positively regulate homologous recombination-mediated DNA repair (PubMed:18086888). MAGEF1-NSMCE1 ubiquitin ligase promotes proteasomal degradation of MMS19, a key component of the cytosolic iron-sulfur protein assembly (CIA) machinery. Down-regulation of MMS19 impairs the activity of several DNA repair and metabolism enzymes such as ERCC2/XPD, FANCJ, RTEL1 and POLD1 that require iron-sulfur clusters as cofactors (PubMed:29225034). {ECO:0000269|PubMed:18086888, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:29225034}.
• 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: 0.104

Intolerance Scores

• loftool: 0.496
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.0800
• hipred: N
• hipred_score: 0.425
• ghis: 0.521

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.350

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nsmce1

Gene ontology

• Biological process: double-strand break repair via homologous recombination;postreplication repair;protein ubiquitination;intracellular signal transduction;positive regulation of response to DNA damage stimulus
• Cellular component: chromosome, telomeric region;nucleus;nucleoplasm;Smc5-Smc6 complex;intracellular membrane-bounded organelle
• Molecular function: ubiquitin-protein transferase activity;protein binding;metal ion binding;protein dimerization activity