NSMCE2 (NSE2 SUMO ligase component of SMC5/6 complex)

Gene

• Entrez ID: 286053
• Gene name: NSE2 SUMO ligase component of SMC5/6 complex
• Gene symbol: NSMCE2
• Synonyms (NCBI Gene): C8orf36, MMS21, NSE2, ZMIZ7
• Chromosome: 8
• Chromosome location: 8q24.13
• Summary: This gene encodes a member of a family of E3 small ubiquitin-related modifier (SUMO) ligases that mediates the attachment of a SUMO protein to proteins involved in nuclear transport, transcription, chromosome segregation and DNA repair. The encoded protei

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs757613817	T>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs760514663	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained
rs773917653	->AGGG	Pathogenic	Frameshift variant, genic downstream transcript variant, non coding transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT677444	hsa-miR-552-3p	HITS-CLIP	23824327
MIRT677443	hsa-miR-3159	HITS-CLIP	23824327
MIRT677442	hsa-miR-6504-3p	HITS-CLIP	23824327
MIRT677441	hsa-miR-764	HITS-CLIP	23824327
MIRT677440	hsa-miR-4740-3p	HITS-CLIP	23824327
MIRT677439	hsa-miR-4722-3p	HITS-CLIP	23824327
MIRT677438	hsa-miR-6727-3p	HITS-CLIP	23824327
MIRT677437	hsa-miR-6747-3p	HITS-CLIP	23824327
MIRT677436	hsa-miR-3653-5p	HITS-CLIP	23824327
MIRT677435	hsa-miR-1976	HITS-CLIP	23824327
MIRT677434	hsa-miR-5095	HITS-CLIP	23824327
MIRT677433	hsa-miR-7151-3p	HITS-CLIP	23824327
MIRT677444	hsa-miR-552-3p	HITS-CLIP	23824327
MIRT677443	hsa-miR-3159	HITS-CLIP	23824327
MIRT677442	hsa-miR-6504-3p	HITS-CLIP	23824327
MIRT677441	hsa-miR-764	HITS-CLIP	23824327
MIRT677440	hsa-miR-4740-3p	HITS-CLIP	23824327
MIRT677439	hsa-miR-4722-3p	HITS-CLIP	23824327
MIRT677438	hsa-miR-6727-3p	HITS-CLIP	23824327
MIRT677437	hsa-miR-6747-3p	HITS-CLIP	23824327
MIRT677436	hsa-miR-3653-5p	HITS-CLIP	23824327
MIRT677435	hsa-miR-1976	HITS-CLIP	23824327
MIRT677434	hsa-miR-5095	HITS-CLIP	23824327
MIRT677433	hsa-miR-7151-3p	HITS-CLIP	23824327
MIRT1195360	hsa-let-7a	CLIP-seq
MIRT1195361	hsa-let-7b	CLIP-seq
MIRT1195362	hsa-let-7c	CLIP-seq
MIRT1195363	hsa-let-7d	CLIP-seq
MIRT1195364	hsa-let-7e	CLIP-seq
MIRT1195365	hsa-let-7f	CLIP-seq
MIRT1195366	hsa-let-7g	CLIP-seq
MIRT1195367	hsa-let-7i	CLIP-seq
MIRT1195368	hsa-miR-1207-3p	CLIP-seq
MIRT1195369	hsa-miR-1324	CLIP-seq
MIRT1195370	hsa-miR-138	CLIP-seq
MIRT1195371	hsa-miR-3065-3p	CLIP-seq
MIRT1195372	hsa-miR-3929	CLIP-seq
MIRT1195373	hsa-miR-421	CLIP-seq
MIRT1195374	hsa-miR-4266	CLIP-seq
MIRT1195375	hsa-miR-4419b	CLIP-seq
MIRT1195376	hsa-miR-4458	CLIP-seq
MIRT1195377	hsa-miR-4478	CLIP-seq
MIRT1195378	hsa-miR-4500	CLIP-seq
MIRT1195379	hsa-miR-4695-5p	CLIP-seq
MIRT1195380	hsa-miR-4709-5p	CLIP-seq
MIRT1195381	hsa-miR-4731-5p	CLIP-seq
MIRT1195382	hsa-miR-4779	CLIP-seq
MIRT1195383	hsa-miR-615-5p	CLIP-seq
MIRT1195384	hsa-miR-98	CLIP-seq
MIRT1195360	hsa-let-7a	CLIP-seq
MIRT1195361	hsa-let-7b	CLIP-seq
MIRT1195362	hsa-let-7c	CLIP-seq
MIRT1195363	hsa-let-7d	CLIP-seq
MIRT1195364	hsa-let-7e	CLIP-seq
MIRT1195365	hsa-let-7f	CLIP-seq
MIRT1195366	hsa-let-7g	CLIP-seq
MIRT1195367	hsa-let-7i	CLIP-seq
MIRT1195368	hsa-miR-1207-3p	CLIP-seq
MIRT2285127	hsa-miR-1305	CLIP-seq
MIRT1195369	hsa-miR-1324	CLIP-seq
MIRT1195370	hsa-miR-138	CLIP-seq
MIRT1195371	hsa-miR-3065-3p	CLIP-seq
MIRT1195372	hsa-miR-3929	CLIP-seq
MIRT1195373	hsa-miR-421	CLIP-seq
MIRT1195374	hsa-miR-4266	CLIP-seq
MIRT2285128	hsa-miR-4307	CLIP-seq
MIRT1195375	hsa-miR-4419b	CLIP-seq
MIRT1195376	hsa-miR-4458	CLIP-seq
MIRT1195377	hsa-miR-4478	CLIP-seq
MIRT1195378	hsa-miR-4500	CLIP-seq
MIRT1195379	hsa-miR-4695-5p	CLIP-seq
MIRT1195380	hsa-miR-4709-5p	CLIP-seq
MIRT1195381	hsa-miR-4731-5p	CLIP-seq
MIRT1195382	hsa-miR-4779	CLIP-seq
MIRT2285129	hsa-miR-4789-3p	CLIP-seq
MIRT2285130	hsa-miR-498	CLIP-seq
MIRT1195384	hsa-miR-98	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000722	Process	Telomere maintenance via recombination	IMP	17589526
GO:0000724	Process	Double-strand break repair via homologous recombination	IBA
GO:0000724	Process	Double-strand break repair via homologous recombination	IEA
GO:0000724	Process	Double-strand break repair via homologous recombination	IMP	16810316
GO:0000724	Process	Double-strand break repair via homologous recombination	NAS	16810316
GO:0000781	Component	Chromosome, telomeric region	IDA	17589526
GO:0000781	Component	Chromosome, telomeric region	IEA
GO:0000781	Component	Chromosome, telomeric region	NAS	17589526
GO:0005515	Function	Protein binding	IPI	18086888, 25416956, 26496610, 32296183, 32814053, 33961781
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0006281	Process	DNA repair	IEA
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IMP	16810316
GO:0006310	Process	DNA recombination	IEA
GO:0006974	Process	DNA damage response	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0016604	Component	Nuclear body	IDA
GO:0016605	Component	PML body	IDA	17589526
GO:0016605	Component	PML body	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016925	Process	Protein sumoylation	IBA
GO:0016925	Process	Protein sumoylation	IEA
GO:0016925	Process	Protein sumoylation	NAS	32389690
GO:0016925	Process	Protein sumoylation	TAS
GO:0019789	Function	SUMO transferase activity	EXP	16055714
GO:0019789	Function	SUMO transferase activity	IDA	17589526
GO:0019789	Function	SUMO transferase activity	IEA
GO:0030915	Component	Smc5-Smc6 complex	IBA
GO:0030915	Component	Smc5-Smc6 complex	IDA	18086888
GO:0030915	Component	Smc5-Smc6 complex	IEA
GO:0030915	Component	Smc5-Smc6 complex	NAS	32389690
GO:0032204	Process	Regulation of telomere maintenance	NAS	17589526
GO:0034184	Process	Positive regulation of maintenance of mitotic sister chromatid cohesion	IMP	19502785
GO:0045842	Process	Positive regulation of mitotic metaphase/anaphase transition	IMP	19502785
GO:0046872	Function	Metal ion binding	IEA
GO:0051301	Process	Cell division	IEA
GO:0061665	Function	SUMO ligase activity	IBA
GO:0090398	Process	Cellular senescence	IMP	17589526
GO:0140588	Process	Chromatin looping	NAS	32389690

Other IDs

• MIM: 617246
• HGNC: 26513
• e!Ensembl: ENSG00000156831

Protein

• UniProt ID: Q96MF7
• Protein name: E3 SUMO-protein ligase NSE2 (EC 2.3.2.-) (E3 SUMO-protein transferase NSE2) (MMS21 homolog) (hMMS21) (Non-structural maintenance of chromosomes element 2 homolog) (Non-SMC element 2 homolog)
• Protein function: E3 SUMO-protein ligase component of the SMC5-SMC6 complex, a complex involved in DNA double-strand break repair by homologous recombination (PubMed:16055714, PubMed:16810316). Is not be required for the stability of the complex (PubMed:16055714,
• PDB: 2YU4
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF11789	zf-Nse	156 → 216	Zinc-finger of the MIZ type in Nse subunit	Domain

• Sequence:

  MPGRSSSNSGSTGFISFSGVESALSSLKNFQACINSGMDTASSVALDLVESQTEVSSEYS
  MDKAMVEFATLDRQLNHYVKAVQSTINHVKEERPEKIPDLKLLVEKKFLALQSKNSDADF
  QNNEKFVQFKQQLKELKKQCGLQADREADGTEGVDEDIIVTQSQTNFTCPITKEEMKKPV
  KNKVCGHTYEEDAIVRMIESRQKRKKKAYCPQIGCSHTDIRKSDLIQDEALRRAIENHNK
  KRHRHSE

• Sequence length: 247

Pathways

Reactome:

SUMOylation of DNA damage response and repair proteins

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Seckel syndrome 10	Likely pathogenic; Pathogenic	rs780276807, rs757613817, rs773917653	RCV003991805 RCV000412505 RCV000412587	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BEHCET'S SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Decreased response to growth hormone stimulation test	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dysmorphic features	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOBLASTOMA MULTIFORME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Global developmental delay	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NSMCE2-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SECKEL SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Short stature	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acanthosis Nigricans	Acanthosis Nigricans	HPO_DG			★☆☆☆☆ Found in Text Mining only
Acute pancreatitis	Pancreatitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm, Abdominal	Aortic Aneurysm	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	22906975		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	36224576	Associate	★☆☆☆☆ Found in Text Mining only
Cap Myopathy	Cap myopathy	Pubtator	22234922	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	19520795	Associate	★☆☆☆☆ Found in Text Mining only
Congenital blindness	Congenital blindness	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	25105364		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Insulin-resistant diabetes mellitus	Insulin-resistant diabetes mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	25245984	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	25245984	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	25245984		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	22906975		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28576919		★☆☆☆☆ Found in Text Mining only
Microcephalic primordial dwarfism-insulin resistance syndrome	Microcephalic Primordial Dwarfism-Insulin Resistance Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Oral Ulcer	Oral Ulcer	GWASCAT_DG	30837455		★☆☆☆☆ Found in Text Mining only
PITUITARY DWARFISM I	Pituitary dwarfism	BEFREE	25105364		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	17978284, 22234922	Associate	★☆☆☆☆ Found in Text Mining only
Retinal Detachment	Retinal Detachment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	27846195		★☆☆☆☆ Found in Text Mining only
SECKEL SYNDROME 10	Seckel Syndrome	GENOMICS_ENGLAND_DG	25105364		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SECKEL SYNDROME 10	Seckel Syndrome	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Severe short-limb dwarfism	Short-Limb Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	30654714	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	21051319	Associate	★☆☆☆☆ Found in Text Mining only
Ventricular hypertrophy	Ventricular hypertrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only