MAD2L2

mitotic arrest deficient 2 like 2, the group of DNA polymerases|FA complementation groups

Basic information

Region (hg38): 1:11657230-11691811

Links

ENSG00000116670 ∙ NCBI:10459 ∙ OMIM:604094 ∙ HGNC:6764 ∙ Uniprot:Q9UI95 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fanconi anemia (Supportive), mode of inheritance: AR
• Fanconi anemia complementation group V (Limited), mode of inheritance: AR
• Fanconi anemia complementation group V (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi anemia, complementation group V	AR	Cardiovascular; Hematologic; Oncologic	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); Individuals may be at risk for certain types of cancer, and awareness may allow early diagnosis and management; Surveillance for complications such as bone marrow failure is recommended; Fanconi anemia can involve congenital cardiac (and other) anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Hematologic; Neurologic; Oncologic	27500492

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAD2L2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAD2L2 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				30	3	33
missense			28	1		29
nonsense						0
start loss			1			1
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)			2			2
splice region			2	17	3	22
non coding			20	33	3	56
Total	0	0	54	64	6

Variants in MAD2L2

This is a list of pathogenic ClinVar variants found in the MAD2L2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-11658275-G-A		not specified	Uncertain significance (Feb 13, 2024)
1-11658368-A-G		not specified	Uncertain significance (Jan 18, 2023)
1-11658589-T-G		not specified	Uncertain significance (May 23, 2023)
1-11658607-C-T		not specified	Uncertain significance (Jul 27, 2022)
1-11658739-C-T		not specified	Likely benign (Apr 30, 2024)
1-11658758-G-A		not specified	Uncertain significance (Jul 13, 2022)
1-11658762-C-T		not specified	Uncertain significance (Dec 20, 2023)
1-11658779-G-A		not specified	Uncertain significance (Jun 02, 2023)
1-11658796-C-T		not specified	Likely benign (Oct 02, 2023)
1-11658839-A-G		not specified	Uncertain significance (Jun 26, 2023)
1-11658850-G-A		not specified	Likely benign (Jan 08, 2024)
1-11661172-A-G		not specified	Uncertain significance (Apr 07, 2022)
1-11661186-C-T		not specified	Likely benign (Dec 13, 2023)
1-11661187-G-A		not specified	Uncertain significance (Jan 26, 2022)
1-11661193-G-A		not specified	Uncertain significance (Aug 18, 2023)
1-11661213-C-T		not specified	Likely benign (Dec 18, 2023)
1-11661244-A-G		not specified	Uncertain significance (Jun 30, 2022)
1-11661252-C-G		not specified	Likely benign (Sep 12, 2023)
1-11661255-C-T		not specified	Likely benign (Dec 26, 2023)
1-11661260-C-G		not specified	Uncertain significance (Dec 21, 2023)
1-11668710-G-A		not specified	Uncertain significance (Jul 12, 2022)
1-11668734-A-G		not specified	Uncertain significance (Jun 30, 2023)
1-11668736-G-A		not specified	Likely benign (Apr 20, 2024)
1-11668746-G-A		not specified	Uncertain significance (Feb 13, 2024)
1-11668796-C-A		not specified	Uncertain significance (May 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAD2L2	protein_coding	protein_coding	ENST00000235310	8	17171

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0821	0.909	125722	0	14	125736	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	81	132	0.615	0.00000804	1388
Missense in Polyphen		17	33.675	0.50482		368
Synonymous	1.01	48	57.8	0.830	0.00000386	409
Loss of Function	2.27	4	12.8	0.313	5.52e-7	142

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000615
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000109	0.000106
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter protein able to interact with different proteins and involved in different biological processes (PubMed:11459825, PubMed:11459826, PubMed:17719540, PubMed:17296730, PubMed:19443654, PubMed:29656893). Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis (PubMed:20164194). Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions (PubMed:20164194). Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) (PubMed:29656893). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection (PubMed:29656893). Mediates various NHEJ- dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres (PubMed:29656893). May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1 (PubMed:17296730). Inhibits the FZR1- and probably CDC20- mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle (PubMed:11459825, PubMed:17719540). Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation (PubMed:19443654). {ECO:0000269|PubMed:11459825, ECO:0000269|PubMed:11459826, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:17719540, ECO:0000269|PubMed:19443654, ECO:0000269|PubMed:20164194, ECO:0000269|PubMed:29656893}.
• Pathway: Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Cell Cycle;DNA Repair;Translesion synthesis by REV1;Translesion synthesis by POLK;Translesion synthesis by POLI;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.395
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.26

Haploinsufficiency Scores

• pHI: 0.866
• hipred: Y
• hipred_score: 0.851
• ghis: 0.510

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mad2l2
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism 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); digestive/alimentary phenotype; reproductive system 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of cell growth;double-strand break repair;actin filament organization;mitotic spindle assembly checkpoint;negative regulation of epithelial to mesenchymal transition;negative regulation of transcription by competitive promoter binding;positive regulation of peptidyl-serine phosphorylation;negative regulation of protein catabolic process;error-prone translesion synthesis;DNA damage response, signal transduction resulting in transcription;negative regulation of DNA-binding transcription factor activity;positive regulation of isotype switching;positive regulation of transcription, DNA-templated;cell division;negative regulation of canonical Wnt signaling pathway;negative regulation of ubiquitin protein ligase activity;negative regulation of double-strand break repair via homologous recombination;negative regulation of cell-cell adhesion mediated by cadherin;negative regulation of transcription regulatory region DNA binding;positive regulation of double-strand break repair via nonhomologous end joining
• Cellular component: nucleus;nucleoplasm;anaphase-promoting complex;chromosome;nucleolus;spindle;cytosol;zeta DNA polymerase complex;site of double-strand break
• Molecular function: RNA polymerase II activating transcription factor binding;protein binding;JUN kinase binding