RAD21

RAD21 cohesin complex component, the group of Cohesin complex|Kleisins|MicroRNA protein coding host genes

Basic information

Region (hg38): 8:116845933-116874776

Links

ENSG00000164754 ∙ NCBI:5885 ∙ OMIM:606462 ∙ HGNC:9811 ∙ Uniprot:O60216 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Cornelia de Lange syndrome 4 (Definitive), mode of inheritance: AD
• Cornelia de Lange syndrome (Supportive), mode of inheritance: AD
• Cornelia de Lange syndrome 4 (Moderate), mode of inheritance: AD
• Mungan syndrome (Limited), mode of inheritance: Unknown
• Cornelia de Lange syndrome 4 (Strong), mode of inheritance: AD
• Cornelia de Lange syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cornelia de Lange syndrome 4; Mungan syndrome	AD/AR	Cardiovascular	The conditions can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dental; Gastrointestinal; Neurologic; Ophthalmologic; Renal	14638363; 17487221; 22633399; 25575569; 31334757

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAD21 gene.

• Cornelia de Lange syndrome 4 (148 variants)
• not provided (136 variants)
• Inborn genetic diseases (57 variants)
• not specified (13 variants)
• Mungan syndrome (4 variants)
• RAD21-related condition (4 variants)
• Cornelia de Lange syndrome 4;Mungan syndrome (3 variants)
• Mungan syndrome;Cornelia de Lange syndrome 4 (2 variants)
• See cases (2 variants)
• De Lange syndrome (1 variants)
• RAD21- Related disorders (1 variants)
• Hereditary cancer-predisposing syndrome (1 variants)
• Acute megakaryoblastic leukemia in down syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAD21 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			2	46	3	51
missense	2	5	80	7		94
nonsense	6	6				12
start loss	1					1
frameshift	12	1				13
inframe indel		1	4	1		6
splice donor/acceptor (+/-2bp)	2		1	1		4
splice region			4	15	8	27
non coding			4	40	42	86
Total	23	13	91	95	45

Variants in RAD21

This is a list of pathogenic ClinVar variants found in the RAD21 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-116847469-A-T			Likely benign (Oct 16, 2018)
8-116847501-T-C		Cornelia de Lange syndrome 4	Uncertain significance (Feb 13, 2023)
8-116847506-A-C		Cornelia de Lange syndrome 4	Uncertain significance (May 05, 2023)
8-116847508-T-C			Uncertain significance (Mar 01, 2024)
8-116847532-C-T		Mungan syndrome	Pathogenic (Dec 13, 2018)
8-116847533-G-A		Cornelia de Lange syndrome 4	Likely benign (Jun 11, 2023)
8-116847533-G-C		Cornelia de Lange syndrome 4	Uncertain significance (Dec 02, 2021)
8-116847538-T-A		Cornelia de Lange syndrome 4	Likely pathogenic (Oct 28, 2021)
8-116847544-T-C		Cornelia de Lange syndrome 4	Uncertain significance (Dec 12, 2019)
8-116847548-C-T		Cornelia de Lange syndrome 4	Likely benign (Jun 08, 2022)
8-116847551-T-C		Cornelia de Lange syndrome 4	Likely benign (Oct 05, 2023)
8-116847553-C-A		Cornelia de Lange syndrome 4	Pathogenic (Oct 09, 2020)
8-116847560-T-G		RAD21-related disorder	Likely benign (Mar 14, 2019)
8-116847572-A-C		Cornelia de Lange syndrome 4	Likely benign (Jan 24, 2023)
8-116847581-C-G		Cornelia de Lange syndrome 4	Uncertain significance (Nov 04, 2023)
8-116847585-T-C		Inborn genetic diseases • Cornelia de Lange syndrome 4	Uncertain significance (Oct 22, 2023)
8-116847588-A-G		Cornelia de Lange syndrome 4	Likely pathogenic (Oct 16, 2012)
8-116847595-A-G		Inborn genetic diseases	Likely benign (May 30, 2019)
8-116847614-G-A		Cornelia de Lange syndrome 4	Conflicting classifications of pathogenicity (Oct 04, 2023)
8-116847619-CTTG-C		Cornelia de Lange syndrome 4	Likely pathogenic (Apr 25, 2018)
8-116847632-C-T			Likely benign (Nov 01, 2021)
8-116847639-C-T		Inborn genetic diseases • Cornelia de Lange syndrome 4	Uncertain significance (Mar 27, 2023)
8-116847643-A-G		Cornelia de Lange syndrome 4	Conflicting classifications of pathogenicity (Feb 02, 2023)
8-116847654-A-G		See cases • Cornelia de Lange syndrome 4	Uncertain significance (Aug 26, 2022)
8-116847661-T-C		Inborn genetic diseases	Likely benign (Aug 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAD21	protein_coding	protein_coding	ENST00000297338	13	28932

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00299	125672	0	4	125676	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.64	204	341	0.598	0.0000173	4208
Missense in Polyphen		27	95.321	0.28325		1159
Synonymous	-0.268	122	118	1.03	0.00000640	1117
Loss of Function	4.60	3	30.3	0.0990	0.00000141	397

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000882	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.0000659	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleavable component of the cohesin complex, involved in chromosome cohesion during cell cycle, in DNA repair, and in apoptosis. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At metaphase-anaphase transition, this protein is cleaved by separase/ESPL1 and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Also plays a role in apoptosis, via its cleavage by caspase-3/CASP3 or caspase-7/CASP7 during early steps of apoptosis: the C-terminal 64 kDa cleavage product may act as a nuclear signal to initiate cytoplasmic events involved in the apoptotic pathway. {ECO:0000269|PubMed:11875078, ECO:0000269|PubMed:12417729}.
• Disease: DISEASE: Cornelia de Lange syndrome 4 (CDLS4) [MIM:614701]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269|PubMed:22633399}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell cycle - Homo sapiens (human);Prion disease pathway;Regulation of sister chromatid separation at the metaphase-anaphase transition;Signal Transduction;SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Reproduction;SUMOylation;Establishment of Sister Chromatid Cohesion;S Phase;Meiotic synapsis;Meiosis;Signaling by Nuclear Receptors;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;Cohesin Loading onto Chromatin;Mitotic Telophase/Cytokinesis;M Phase;Estrogen-dependent gene expression;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;ESR-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.193

Intolerance Scores

• loftool: 0.416
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.41

Haploinsufficiency Scores

• pHI: 0.970
• hipred: Y
• hipred_score: 0.783
• ghis: 0.644

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rad21
• Phenotype: 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); reproductive system phenotype; hematopoietic system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: rad21a
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: increased accumulation

Gene ontology

• Biological process: double-strand break repair;DNA recombination;regulation of transcription by RNA polymerase II;apoptotic process;sister chromatid cohesion;reciprocal meiotic recombination;negative regulation of G2/M transition of mitotic cell cycle;negative regulation of mitotic metaphase/anaphase transition;positive regulation of sister chromatid cohesion;cell division;meiotic cell cycle;protein localization to chromatin
• Cellular component: chromosome, centromeric region;chromatin;condensed nuclear chromosome;nucleoplasm;chromosome;cytosol;cohesin complex;membrane;nuclear matrix;meiotic cohesin complex
• Molecular function: chromatin binding;protein binding