NIPBL
NIPBL cohesin loading factor, the group of Armadillo like helical domain containing
Basic information
Region (hg38): 5:36876768-37066413
Links
Phenotypes
GenCC
Source:
- Cornelia de Lange syndrome 1 (Definitive), mode of inheritance: AD
- Cornelia de Lange syndrome 1 (Strong), mode of inheritance: AD
- Cornelia de Lange syndrome (Supportive), mode of inheritance: AD
- Cornelia de Lange syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cornelia de Lange syndrome 1 | AD | Cardiovascular | The condition can involve congenital cardiac anomalies, and awareness may allow early management | Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Renal | 2246693; 2333897; 8291513; 8281279; 8291537; 8291518; 9279756; 12784293; 15146185; 15146186; 15633188; 16236812; 16770807; 17661813; 20301283; 20358602; 20583156; 22241092; 22581668; 22676896; 22965847; 23254390; 23304577; 23313159; 23505322 |
| Somatic mosaicism is relatively frequent |
ClinVar
This is a list of variants' phenotypes submitted to
- Cornelia de Lange syndrome 1 (983 variants)
- not provided (447 variants)
- Inborn genetic diseases (185 variants)
- not specified (121 variants)
- NIPBL-related condition (34 variants)
- De Lange syndrome (13 variants)
- Intellectual disability (5 variants)
- See cases (3 variants)
- Orofacial cleft 1 (1 variants)
- Global developmental delay (1 variants)
- Abnormal brain morphology (1 variants)
- Global developmental delay;Intellectual disability;Brachydactyly;Abnormal facial shape (1 variants)
- Neurodevelopmental disorder (1 variants)
- Tetralogy of Fallot;Cleft palate;Microcephaly (1 variants)
- Neurodevelopmental delay (1 variants)
- 9 conditions (1 variants)
- History of neurodevelopmental disorder (1 variants)
- Intellectual disability, mild;Seizure;Plagiocephaly;Horseshoe kidney;Vesicoureteral reflux (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NIPBL 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 | 40 | 160 | 10 | 212 | ||
| missense | 20 | 58 | 382 | 56 | 522 | |
| nonsense | 99 | 12 | 111 | |||
| start loss | 2 | |||||
| frameshift | 166 | 13 | 180 | |||
| inframe indel | 11 | 15 | 29 | |||
| splice donor/acceptor (+/-2bp) | 39 | 16 | 57 | |||
| splice region ? | 9 | 11 | 23 | 29 | 2 | 74 |
| non coding ? | 24 | 114 | 82 | 222 | ||
| Total | 328 | 114 | 462 | 333 | 98 |
Variants in NIPBL
This is a list of pathogenic ClinVar variants found in the NIPBL region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-36876791-C-T | Cornelia de Lange syndrome 1 | Pathogenic/Likely pathogenic (Feb 11, 2022) | ||
| 5-36876801-GA-AT | Neurodevelopmental abnormality | Likely pathogenic (Oct 22, 2021) | ||
| 5-36876823-TC-T | De Lange syndrome | Likely benign (Jun 14, 2016) | ||
| 5-36876830-G-C | Cornelia de Lange syndrome 1 | Uncertain significance (Jan 13, 2018) | ||
| 5-36876834-T-C | Cornelia de Lange syndrome 1 | Uncertain significance (Jan 13, 2018) | ||
| 5-36876834-T-TC | De Lange syndrome | Conflicting classifications of pathogenicity (Feb 01, 2023) | ||
| 5-36876842-CT-C | Benign (Jan 01, 2023) | |||
| 5-36876848-C-T | Cornelia de Lange syndrome 1 | Uncertain significance (Jan 13, 2018) | ||
| 5-36876879-G-A | Cornelia de Lange syndrome 1 | Uncertain significance (Jan 12, 2018) | ||
| 5-36876920-C-T | Cornelia de Lange syndrome 1 | Uncertain significance (Jan 13, 2018) | ||
| 5-36876936-GC-G | Cornelia de Lange syndrome 1 | Uncertain significance (Dec 30, 2023) | ||
| 5-36876937-CC-A | Cornelia de Lange syndrome 1 | Pathogenic (Aug 01, 2006) | ||
| 5-36876938-C-A | Cornelia de Lange syndrome 1 | Pathogenic (Nov 14, 2021) | ||
| 5-36876946-T-A | Cornelia de Lange syndrome 1 | Likely benign (Feb 01, 2024) | ||
| 5-36876951-C-T | Cornelia de Lange syndrome 1 | Benign (Jan 13, 2018) | ||
| 5-36876993-A-G | Cornelia de Lange syndrome 1 | Uncertain significance (Jan 13, 2018) | ||
| 5-36877015-A-C | Cornelia de Lange syndrome 1 | Benign (Jan 13, 2018) | ||
| 5-36877098-A-AC | De Lange syndrome | Uncertain significance (Jun 14, 2016) | ||
| 5-36877180-TA-T | not specified | Likely benign (Jan 01, 2023) | ||
| 5-36877189-G-C | Cornelia de Lange syndrome 1 | Uncertain significance (Jan 12, 2018) | ||
| 5-36942059-C-T | Cornelia de Lange syndrome 1 | Uncertain significance (Feb 26, 2021) | ||
| 5-36952018-CTG-C | Benign (Jul 01, 2022) | |||
| 5-36952018-CTGTGTG-C | Likely benign (Nov 01, 2023) | |||
| 5-36952018-CTGTGTGTG-C | Benign (Oct 01, 2022) | |||
| 5-36952018-C-CTGTGTGTGTGTGTGTG | Benign (Dec 01, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NIPBL | protein_coding | protein_coding | ENST00000282516 | 46 | 189655 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 3.57e-24 | 125693 | 0 | 3 | 125696 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 5.57 | 846 | 1.44e+3 | 0.587 | 0.0000738 | 18540 |
| Missense in Polyphen | 158 | 543.1 | 0.29092 | 7135 | ||
| Synonymous | -0.0351 | 496 | 495 | 1.00 | 0.0000249 | 5211 |
| Loss of Function | 11.3 | 1 | 150 | 0.00665 | 0.00000942 | 1781 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| 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 | 0.0000653 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitement to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitement to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}.;
- Disease
- DISEASE: Cornelia de Lange syndrome 1 (CDLS1) [MIM:122470]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269|PubMed:15146185, ECO:0000269|PubMed:15146186, ECO:0000269|PubMed:15318302, ECO:0000269|PubMed:20124326, ECO:0000269|PubMed:20358602, ECO:0000269|PubMed:21934712, ECO:0000269|PubMed:23254390, ECO:0000269|PubMed:25447906, ECO:0000269|PubMed:28167679}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Cohesin Loading onto Chromatin;Mitotic Telophase/Cytokinesis;M Phase;Cell Cycle;Cell Cycle, Mitotic
(Consensus)
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- loftool
- 0.0000689
- rvis_EVS
- -2.45
- rvis_percentile_EVS
- 1.01
Haploinsufficiency Scores
- pHI
- 0.943
- hipred
- Y
- hipred_score
- 0.859
- ghis
- 0.678
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.992
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nipbl
- Phenotype
- growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; craniofacial phenotype; vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype;
Zebrafish Information Network
- Gene name
- nipbla
- Affected structure
- post-vent region
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;metanephros development;heart morphogenesis;outflow tract morphogenesis;double-strand break repair;cellular response to DNA damage stimulus;mitotic sister chromatid cohesion;mitotic chromosome condensation;brain development;heart development;sensory perception of sound;stem cell population maintenance;positive regulation of histone deacetylation;establishment of mitotic sister chromatid cohesion;maintenance of mitotic sister chromatid cohesion;cellular protein localization;embryonic forelimb morphogenesis;forelimb morphogenesis;external genitalia morphogenesis;positive regulation of multicellular organism growth;ear morphogenesis;regulation of hair cycle;fat cell differentiation;positive regulation of ossification;negative regulation of transcription, DNA-templated;regulation of embryonic development;embryonic digestive tract morphogenesis;developmental growth;eye morphogenesis;regulation of developmental growth;embryonic viscerocranium morphogenesis;cognition;face morphogenesis;gall bladder development;uterus morphogenesis;rDNA condensation;establishment of protein localization to chromatin;cellular response to X-ray;transcriptional activation by promoter-enhancer looping;cohesin loading;positive regulation of mitotic cohesin loading;replication-born double-strand break repair via sister chromatid exchange;positive regulation of neuron migration
- Cellular component
- nuclear chromosome;chromatin;nuclear chromatin;nucleus;nucleoplasm;integrator complex;SMC loading complex;extracellular exosome;Scc2-Scc4 cohesin loading complex
- Molecular function
- chromatin binding;protein binding;protein C-terminus binding;mediator complex binding;histone deacetylase binding;protein N-terminus binding;chromo shadow domain binding