NHEJ1 (non-homologous end joining factor 1)

Gene

• Entrez ID: 79840
• Gene name: Non-homologous end joining factor 1
• Gene symbol: NHEJ1
• Synonyms (NCBI Gene): IMD124, MCOPCB13, XLF
• Chromosome: 2
• Chromosome location: 2q35
• Summary: Double-strand breaks in DNA result from genotoxic stresses and are among the most damaging of DNA lesions. This gene encodes a DNA repair factor essential for the nonhomologous end-joining pathway, which preferentially mediates repair of double-stranded b

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs118204451	G>A,C	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant, missense variant
rs118204452	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs118204453	G>A,T	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant, synonymous variant
rs786205547	C>G	Likely-pathogenic	Splice donor variant
rs886037606	TAC>AA	Pathogenic	Splice donor variant, intron variant
rs886037607	->A	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs886041973	->C	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1064793763	T>A	Pathogenic	Splice acceptor variant
rs1064796857	AATC>-	Likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1064797028	A>C	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1064797042	A>-	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1553542017	G>A	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs1553548393	->TTCC	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1184236	hsa-miR-193a-5p	CLIP-seq
MIRT1184237	hsa-miR-3064-5p	CLIP-seq
MIRT1184238	hsa-miR-3126-3p	CLIP-seq
MIRT1184239	hsa-miR-3150b-3p	CLIP-seq
MIRT1184240	hsa-miR-3652	CLIP-seq
MIRT1184241	hsa-miR-3921	CLIP-seq
MIRT1184242	hsa-miR-4283	CLIP-seq
MIRT1184243	hsa-miR-4311	CLIP-seq
MIRT1184244	hsa-miR-4430	CLIP-seq
MIRT1184245	hsa-miR-4433	CLIP-seq
MIRT1184246	hsa-miR-4489	CLIP-seq
MIRT1184247	hsa-miR-4492	CLIP-seq
MIRT1184248	hsa-miR-4498	CLIP-seq
MIRT1184249	hsa-miR-4505	CLIP-seq
MIRT1184250	hsa-miR-4649-3p	CLIP-seq
MIRT1184251	hsa-miR-4653-5p	CLIP-seq
MIRT1184252	hsa-miR-4667-5p	CLIP-seq
MIRT1184253	hsa-miR-4689	CLIP-seq
MIRT1184254	hsa-miR-4700-5p	CLIP-seq
MIRT1184255	hsa-miR-4784	CLIP-seq
MIRT1184256	hsa-miR-4794	CLIP-seq
MIRT1184257	hsa-miR-4795-5p	CLIP-seq
MIRT1184258	hsa-miR-593	CLIP-seq
MIRT1184259	hsa-miR-637	CLIP-seq
MIRT1184260	hsa-miR-661	CLIP-seq
MIRT1184261	hsa-miR-665	CLIP-seq
MIRT1184262	hsa-miR-762	CLIP-seq
MIRT2053440	hsa-miR-3122	CLIP-seq
MIRT2053441	hsa-miR-34c-3p	CLIP-seq
MIRT2053442	hsa-miR-3689a-3p	CLIP-seq
MIRT2053443	hsa-miR-3689c	CLIP-seq
MIRT2053444	hsa-miR-3913-5p	CLIP-seq
MIRT1184245	hsa-miR-4433	CLIP-seq
MIRT2053445	hsa-miR-4728-5p	CLIP-seq
MIRT2053446	hsa-miR-541	CLIP-seq
MIRT2053447	hsa-miR-654-5p	CLIP-seq
MIRT1184261	hsa-miR-665	CLIP-seq
MIRT2282648	hsa-miR-1285	CLIP-seq
MIRT2282649	hsa-miR-214	CLIP-seq
MIRT2053440	hsa-miR-3122	CLIP-seq
MIRT2282650	hsa-miR-3187-5p	CLIP-seq
MIRT2053441	hsa-miR-34c-3p	CLIP-seq
MIRT2282651	hsa-miR-3619-5p	CLIP-seq
MIRT2053442	hsa-miR-3689a-3p	CLIP-seq
MIRT2053443	hsa-miR-3689c	CLIP-seq
MIRT2282652	hsa-miR-3691-3p	CLIP-seq
MIRT2282653	hsa-miR-3913-3p	CLIP-seq
MIRT2053444	hsa-miR-3913-5p	CLIP-seq
MIRT2282654	hsa-miR-4291	CLIP-seq
MIRT1184243	hsa-miR-4311	CLIP-seq
MIRT1184245	hsa-miR-4433	CLIP-seq
MIRT2282655	hsa-miR-4436a	CLIP-seq
MIRT2053445	hsa-miR-4728-5p	CLIP-seq
MIRT2282656	hsa-miR-489	CLIP-seq
MIRT2282657	hsa-miR-516a-5p	CLIP-seq
MIRT2053446	hsa-miR-541	CLIP-seq
MIRT2282658	hsa-miR-612	CLIP-seq
MIRT2282659	hsa-miR-646	CLIP-seq
MIRT2053447	hsa-miR-654-5p	CLIP-seq
MIRT1184260	hsa-miR-661	CLIP-seq
MIRT1184261	hsa-miR-665	CLIP-seq
MIRT2282660	hsa-miR-761	CLIP-seq
MIRT2282661	hsa-miR-922	CLIP-seq
MIRT2455135	hsa-miR-3145-3p	CLIP-seq
MIRT2455136	hsa-miR-3173-3p	CLIP-seq
MIRT2455137	hsa-miR-3612	CLIP-seq
MIRT2455138	hsa-miR-4428	CLIP-seq
MIRT2455139	hsa-miR-4695-5p	CLIP-seq
MIRT2455140	hsa-miR-650	CLIP-seq
MIRT2053440	hsa-miR-3122	CLIP-seq
MIRT2053442	hsa-miR-3689a-3p	CLIP-seq
MIRT2053443	hsa-miR-3689c	CLIP-seq
MIRT2053444	hsa-miR-3913-5p	CLIP-seq
MIRT2053445	hsa-miR-4728-5p	CLIP-seq
MIRT2053446	hsa-miR-541	CLIP-seq
MIRT2053447	hsa-miR-654-5p	CLIP-seq
MIRT2053440	hsa-miR-3122	CLIP-seq
MIRT2053442	hsa-miR-3689a-3p	CLIP-seq
MIRT2053443	hsa-miR-3689c	CLIP-seq
MIRT2053444	hsa-miR-3913-5p	CLIP-seq
MIRT2053445	hsa-miR-4728-5p	CLIP-seq
MIRT2053446	hsa-miR-541	CLIP-seq
MIRT2053447	hsa-miR-654-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000723	Process	Telomere maintenance	IMP	28369633
GO:0001650	Component	Fibrillar center	IDA
GO:0003677	Function	DNA binding	IEA
GO:0005515	Function	Protein binding	IPI	16439205, 18064046, 18158905, 21070942, 21349273, 21768349, 24095731, 27437582, 28500754, 29997244, 31548606
GO:0005634	Component	Nucleus	IDA	20558749
GO:0005634	Component	Nucleus	IDA	16439204, 16439205
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0005958	Component	DNA-dependent protein kinase-DNA ligase 4 complex	IDA	34352203
GO:0006281	Process	DNA repair	IEA
GO:0006302	Process	Double-strand break repair	IEA
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IBA
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IDA	17717001, 18158905, 18644470, 19056826, 20558749, 27437582, 28500754, 30250067
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IEA
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IMP	16439204, 16439205
GO:0006974	Process	DNA damage response	IEA
GO:0007417	Process	Central nervous system development	NAS	16439204
GO:0010212	Process	Response to ionizing radiation	IDA	16439205
GO:0030183	Process	B cell differentiation	IMP	16439204
GO:0030217	Process	T cell differentiation	IMP	16439204
GO:0032807	Component	DNA ligase IV complex	IBA
GO:0033152	Process	Immunoglobulin V(D)J recombination	IDA	20558749
GO:0035861	Component	Site of double-strand break	IDA	18064046, 18644470, 27437582, 28500754
GO:0045027	Function	DNA end binding	IBA
GO:0045027	Function	DNA end binding	IDA	18158905
GO:0051351	Process	Positive regulation of ligase activity	NAS	16439205
GO:0070182	Function	DNA polymerase binding	IPI	30250067
GO:0070419	Component	Nonhomologous end joining complex	IDA	20383123, 25941166

Other IDs

• MIM: 611290
• HGNC: 25737
• e!Ensembl: ENSG00000187736

Protein

• UniProt ID: Q9H9Q4
• Protein name: Non-homologous end-joining factor 1 (Protein cernunnos) (XRCC4-like factor)
• Protein function: DNA repair protein involved in DNA non-homologous end joining (NHEJ); it is required for double-strand break (DSB) repair and V(D)J recombination and is also involved in telomere maintenance (PubMed:16439204, PubMed:16439205, PubMed:17317666, Pu
• PDB: 2QM4, 2R9A, 3Q4F, 3RWR, 3SR2, 3W03, 6ERG, 6ERH, 7LSY, 7LT3, 7NFC, 7NFE, 7ZYG, 8BHV, 8BHY, 8BOT, 8EZA, 8EZB
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF09302	XLF	12 → 182	XLF-Cernunnos, XRcc4-like factor, NHEJ component	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed. {ECO:0000269|PubMed:16439204}.
• Sequence:

  MEELEQGLLMQPWAWLQLAENSLLAKVFITKQGYALLVSDLQQVWHEQVDTSVVSQRAKE
  LNKRLTAPPAAFLCHLDNLLRPLLKDAAHPSEATFSCDCVADALILRVRSELSGLPFYWN
  FHCMLASPSLVSQHLIRPLMGMSLALQCQVRELATLLHMKDLEIQDYQESGATLIRDRLK
  TEPFEENSFLEQFMIEKLPEACSIGDGKPFVMNLQDLYMAVTTQEVQVGQKHQGAGDPHT
  SNSASLQGIDSQCVNQPEQLVSSAPTLSAPEKESTGTSGPLQRPQLSKVKRKKPRGLFS

• Sequence length: 299

Pathways

KEGG:

Non-homologous end-joining

Reactome:

Nonhomologous End-Joining (NHEJ)

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
Cernunnos-XLF deficiency	Pathogenic; Likely pathogenic	rs118204451, rs1481152382, rs2106320090, rs146783338, rs118204452, rs118204453, rs886037606, rs886037607, rs1949876445, rs786205547, rs2469678006, rs2106369643, rs777740338, rs1304446470, rs1430712125, rs1949876985, rs1064793763, rs1553542017, rs1949865586, rs753495484, rs1949868667	RCV004691645 RCV001979683 RCV002002421 RCV002003384 RCV000001033 RCV000001034 RCV000001035 RCV001851523 RCV002283930 RCV002898584 RCV002871770 RCV002922632 RCV003054322 RCV003494647 RCV003821627 RCV003872391 RCV002283483 RCV000645373 RCV001048737 RCV001046665 RCV001218042	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Isolated anophthalmia-microphthalmia syndrome	Likely pathogenic	rs1574729059	RCV003236670	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microphthalmia/coloboma 13	Likely pathogenic	rs1574729059	RCV004731275	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Severe combined immunodeficiency disease	Pathogenic	rs886037607	RCV004799725	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DUODENAL ULCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 124, SEVERE COMBINED	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NHEJ1-related disorder	Conflicting classifications of pathogenicity; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, KNEE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PEPTIC ULCER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE COMBINED IMMUNODEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE COMBINED IMMUNODEFICIENCY WITH MICROCEPHALY, GROWTH RETARDATION, AND SENSITIVITY TO IONIZING RADIATION	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE COMBINED IMMUNODEFICIENCY, MICROCEPHALY, GROWTH RETARDATION, SENSITIVITY TO IONIZING RADIATION SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYNDACTYLY, TYPE I	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia Hemolytic Autoimmune	Autoimmune hemolytic anemia	Pubtator	30898087	Associate	★☆☆☆☆ Found in Text Mining only
Aplastic Anemia	Aplastic anemia	BEFREE	28369633		★☆☆☆☆ Found in Text Mining only
Ataxia Telangiectasia	Ataxia Telangiectasia	LHGDN	18644470		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	26225792	Associate	★☆☆☆☆ Found in Text Mining only
Cernunnos-XLF deficiency	Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Colorectal Carcinoma	Colorectal Cancer	BEFREE	30936724, 31806933		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	31806933	Associate	★☆☆☆☆ Found in Text Mining only
Combined immunodeficiency	Severe combined immunodeficiency disease	BEFREE	28741180		★☆☆☆☆ Found in Text Mining only
Combined immunodeficiency	Severe combined immunodeficiency disease	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	25321468	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	31819508		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	31819508		★☆☆☆☆ Found in Text Mining only
Graft vs Host Disease	Graft-versus-host disease	Pubtator	17317666, 19223975	Associate	★☆☆☆☆ Found in Text Mining only
Hematologic Diseases	Hematologic disease	Pubtator	35812385	Associate	★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	26255102, 28741180		★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	28526069		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	17191205, 19223975, 22373003, 28846869		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	19223975, 30898087	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microphthalmia Syndromic 6	Microphthalmia	Pubtator	19223975	Associate	★☆☆☆☆ Found in Text Mining only
Nijmegen Breakage Syndrome	Nijmegen Breakage Syndrome	BEFREE	20597108		★☆☆☆☆ Found in Text Mining only
Pancytopenia	Pancytopenia	BEFREE	28369633		★☆☆☆☆ Found in Text Mining only
Polymicrogyria	Polymicrogyria	BEFREE	17191205		★☆☆☆☆ Found in Text Mining only
Seckel syndrome 1	Seckel syndrome	Pubtator	35812385	Associate	★☆☆☆☆ Found in Text Mining only
Severe Combined Immunodeficiency	Severe combined immunodeficiency	Pubtator	17317666, 30898087, 32265901, 32691468, 35303369, 40457861	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe Combined Immunodeficiency	Severe combined immunodeficiency disease	BEFREE	30898087		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe Combined Immunodeficiency with Microcephaly, Growth Retardation, and Sensitivity to Ionizing Radiation	Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation	GENOMICS_ENGLAND_DG	16439204		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe Combined Immunodeficiency with Microcephaly, Growth Retardation, and Sensitivity to Ionizing Radiation	Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation	UNIPROT_DG	16439204, 16439205, 17317666		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe Combined Immunodeficiency with Microcephaly, Growth Retardation, and Sensitivity to Ionizing Radiation	Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation	BEFREE	22373003		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe Combined Immunodeficiency with Microcephaly, Growth Retardation, and Sensitivity to Ionizing Radiation	Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe Combined Immunodeficiency with Microcephaly, Growth Retardation, and Sensitivity to Ionizing Radiation	Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe Combined Immunodeficiency with Microcephaly, Growth Retardation, and Sensitivity to Ionizing Radiation	Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	29522271		★☆☆☆☆ Found in Text Mining only
Werner Syndrome	Werner syndrome	Pubtator	24626809	Inhibit	★☆☆☆☆ Found in Text Mining only