MDC1

mediator of DNA damage checkpoint 1

Basic information

Region (hg38): 6:30699807-30717447

Links

ENSG00000137337 ∙ NCBI:9656 ∙ OMIM:607593 ∙ HGNC:21163 ∙ Uniprot:Q14676 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MDC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MDC1 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				3	6	9
missense			72	11	6	89
nonsense						0
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	72	14	13

Variants in MDC1

This is a list of pathogenic ClinVar variants found in the MDC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-30700586-G-C		not specified	Uncertain significance (May 30, 2024)
6-30700597-G-A			Benign (Aug 14, 2020)
6-30702765-C-T		not specified	Uncertain significance (Jan 25, 2023)
6-30702771-C-T		not specified	Likely benign (Jun 13, 2023)
6-30702787-C-T		not specified	Uncertain significance (Nov 07, 2022)
6-30703174-C-T		not specified	Uncertain significance (Feb 22, 2023)
6-30703175-G-A		not specified	Uncertain significance (Feb 21, 2024)
6-30703210-G-A		not specified	Likely benign (May 23, 2024)
6-30703222-A-G		not specified	Uncertain significance (Jul 30, 2023)
6-30703429-T-C			Benign (Jun 15, 2018)
6-30703435-C-T		not specified	Uncertain significance (May 21, 2024)
6-30703452-C-T			Benign (Nov 01, 2023)
6-30703467-C-T		not specified	Likely benign (Jun 28, 2022)
6-30703639-C-G		not specified	Uncertain significance (Jun 30, 2022)
6-30703662-C-T		not specified	Uncertain significance (Mar 30, 2024)
6-30703749-T-C		not specified	Uncertain significance (Jun 13, 2022)
6-30703751-C-T		not specified	Uncertain significance (Feb 15, 2023)
6-30703829-G-A		not specified	Uncertain significance (Sep 21, 2023)
6-30703863-C-T		not specified	Uncertain significance (Jul 26, 2021)
6-30703890-C-T		not specified	Uncertain significance (Mar 20, 2023)
6-30703940-G-A		not specified	Uncertain significance (Oct 06, 2021)
6-30703940-G-C		not specified	Uncertain significance (May 13, 2024)
6-30703970-T-A		not specified	Likely benign (Jun 28, 2022)
6-30704051-G-A			Uncertain significance (Jan 12, 2022)
6-30704051-G-T		not specified	Uncertain significance (Feb 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MDC1	protein_coding	protein_coding	ENST00000376406	14	18083

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.27e-8	1.00	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.79	942	1.11e+3	0.849	0.0000568	13371
Missense in Polyphen		258	332.65	0.77559		4072
Synonymous	2.55	361	428	0.843	0.0000218	4542
Loss of Function	4.58	25	64.7	0.386	0.00000342	790

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000218	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000470	0.0000462
European (Non-Finnish)	0.000163	0.000158
Middle Eastern	0.000218	0.000217
South Asian	0.000165	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. May serve as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage marked by 'Ser-139' phosphorylation of histone H2AFX. Also required for downstream events subsequent to the recruitment of these proteins. These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1. {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652}.
• Pathway: TP53 Regulates Transcription of DNA Repair Genes;ATM Signaling Network in Development and Disease;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;Generic Transcription Pathway;SUMOylation of DNA damage response and repair proteins;Homology Directed Repair;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;SUMOylation;TP53 Regulates Transcription of DNA Repair Genes;Transcriptional Regulation by TP53;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Processing of DNA double-strand break ends;ATM pathway (Consensus)

Intolerance Scores

• loftool: 0.630
• rvis_EVS: 5.2
• rvis_percentile_EVS: 99.83

Haploinsufficiency Scores

• pHI: 0.744
• hipred: Y
• hipred_score: 0.519
• ghis: 0.511

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.951

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mdc1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; immune system phenotype; hematopoietic system 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)

Gene ontology

• Biological process: double-strand break repair via nonhomologous end joining;intra-S DNA damage checkpoint
• Cellular component: nucleus;nucleoplasm;chromosome;focal adhesion;nuclear body
• Molecular function: protein binding;protein C-terminus binding;identical protein binding;FHA domain binding