MAD1L1

mitotic arrest deficient 1 like 1, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 7:1815792-2233243

Links

ENSG00000002822 ∙ NCBI:8379 ∙ OMIM:602686 ∙ HGNC:6762 ∙ Uniprot:Q9Y6D9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition (Limited), mode of inheritance: AR
• familial prostate carcinoma (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition	AR	Oncologic	The condition can involve increased risk of a variaty of neoplasms, and awareness may allow early detection and management	Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic	36322655

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAD1L1 gene.

• Mosaic variegated aneuploidy syndrome 1 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAD1L1 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				4	3	7
missense			42	3	1	46
nonsense	1					1
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1	1	2
Total	2	0	42	8	5

Highest pathogenic variant AF is 0.0000263

Variants in MAD1L1

This is a list of pathogenic ClinVar variants found in the MAD1L1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-1816074-G-A		not specified	Uncertain significance (Dec 09, 2023)
7-1816078-C-T		not specified	Uncertain significance (Feb 06, 2023)
7-1816099-C-T		not specified	Uncertain significance (Nov 03, 2022)
7-1816144-G-A		not specified	Uncertain significance (Aug 08, 2022)
7-1816196-T-C			Likely benign (Mar 01, 2022)
7-1816238-A-G			Likely benign (Dec 31, 2019)
7-1898201-T-C		not specified	Uncertain significance (Jun 28, 2022)
7-1898203-G-C		not specified	Uncertain significance (Sep 14, 2021)
7-1898239-C-T			Benign (Dec 31, 2019)
7-1898240-G-C		not specified	Uncertain significance (Apr 08, 2022)
7-1898249-C-A		not specified	Uncertain significance (May 01, 2022)
7-1898250-G-A		Mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition	Uncertain significance (Mar 14, 2024)
7-1898251-G-C		LYMPHOMA, DIFFUSE LARGE B-CELL, SOMATIC	Pathogenic (May 31, 2001)
7-1898316-C-A		Mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition	Pathogenic (Jan 12, 2023)
7-1898318-T-C		not specified	Uncertain significance (Apr 20, 2023)
7-1898364-C-T		not specified	Uncertain significance (Apr 27, 2022)
7-1936704-G-A		not specified	Uncertain significance (Oct 29, 2021)
7-1936744-C-G		not specified	Uncertain significance (Feb 22, 2023)
7-1936765-C-T		not specified	Uncertain significance (Feb 05, 2024)
7-1936827-C-A		not specified	Uncertain significance (Mar 13, 2023)
7-1936848-G-T		not specified	Uncertain significance (Sep 27, 2022)
7-1957639-C-T		not specified	Uncertain significance (Sep 01, 2021)
7-1957685-G-A		not specified	Uncertain significance (Oct 21, 2021)
7-1980483-A-G		not specified	Uncertain significance (Dec 13, 2023)
7-1980497-G-A			Likely benign (Oct 24, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAD1L1	protein_coding	protein_coding	ENST00000406869	17	417450

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.84e-16	0.567	124762	0	114	124876	0.000457

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0252	460	462	0.997	0.0000317	4660
Missense in Polyphen		136	139.42	0.97545		1508
Synonymous	-0.809	210	196	1.07	0.0000136	1373
Loss of Function	1.71	30	42.0	0.715	0.00000204	465

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000790	0.000781
Ashkenazi Jewish	0.000116	0.0000993
East Asian	0.000452	0.000445
Finnish	0.000422	0.000417
European (Non-Finnish)	0.000543	0.000538
Middle Eastern	0.000452	0.000445
South Asian	0.000491	0.000490
Other	0.000665	0.000659

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. May recruit MAD2L1 to unattached kinetochores. Has a role in the correct positioning of the septum. Required for anchoring MAD2L1 to the nuclear periphery. Binds to the TERT promoter and represses telomerase expression, possibly by interfering with MYC binding. {ECO:0000269|PubMed:10049595, ECO:0000269|PubMed:12837246, ECO:0000269|PubMed:20133940}.
• Disease: DISEASE: Note=Defects in MAD1L1 are involved in the development and/or progression of various types of cancer. {ECO:0000269|PubMed:10597320, ECO:0000269|PubMed:11423979}.
• Pathway: Cell cycle - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Cell Cycle;Regulation of sister chromatid separation at the metaphase-anaphase transition;Signal Transduction;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;C-MYB transcription factor network;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.924
• rvis_EVS: -1.32
• rvis_percentile_EVS: 4.76

Haploinsufficiency Scores

• pHI: 0.614
• hipred: N
• hipred_score: 0.498
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.850

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mad1l1
• 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); neoplasm; endocrine/exocrine gland phenotype; cellular phenotype

Gene ontology

• Biological process: mitotic cell cycle checkpoint;mitotic spindle assembly checkpoint;negative regulation of T cell proliferation;thymus development;cell division;attachment of mitotic spindle microtubules to kinetochore;regulation of metaphase plate congression
• Cellular component: kinetochore;condensed chromosome kinetochore;nuclear envelope;centrosome;spindle;cytosol;nuclear pore nuclear basket;mitotic spindle;mitotic spindle pole
• Molecular function: protein binding;identical protein binding;kinetochore binding