MCM9

minichromosome maintenance 9 homologous recombination repair factor, the group of MCM family

Basic information

Region (hg38): 6:118813442-118935162

Previous symbols: [ "MCMDC1", "C6orf61" ]

Links

ENSG00000111877 ∙ NCBI:254394 ∙ OMIM:610098 ∙ HGNC:21484 ∙ Uniprot:Q9NXL9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 46,XX ovarian dysgenesis-short stature syndrome (Supportive), mode of inheritance: AR
• 46,XX ovarian dysgenesis-short stature syndrome (Strong), mode of inheritance: AR
• 46,XX ovarian dysgenesis-short stature syndrome (Moderate), mode of inheritance: AR
• 46,XX ovarian dysgenesis-short stature syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ovarian dysgenesis 4	AR	Endocrine	Awareness may allow medical management (eg, with combined estrogen-progestin therapy) in order to benefit pubertal development and growth	Endocrine	25480036

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCM9 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCM9 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				6	4	10
missense			58	13	7	78
nonsense		1	1			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding			7	1		8
Total	0	2	66	20	11

Variants in MCM9

This is a list of pathogenic ClinVar variants found in the MCM9 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-118814831-T-C		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
6-118814836-T-A		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
6-118814837-C-A		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
6-118814839-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 08, 2024)
6-118814925-C-T		Inborn genetic diseases	Uncertain significance (Sep 07, 2022)
6-118814936-C-T		Inborn genetic diseases	Likely benign (Aug 16, 2021)
6-118814937-G-A		Inborn genetic diseases	Uncertain significance (Aug 17, 2021)
6-118814958-T-C		Inborn genetic diseases	Uncertain significance (Apr 20, 2023)
6-118814966-C-T		Inborn genetic diseases	Uncertain significance (Jul 07, 2022)
6-118814970-T-C		MCM9-related disorder	Likely benign (Dec 31, 2019)
6-118815000-G-T		Inborn genetic diseases	Uncertain significance (May 17, 2023)
6-118815024-T-C		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
6-118815033-G-A			Benign (Dec 01, 2023)
6-118815114-C-T		Inborn genetic diseases	Likely benign (Oct 12, 2021)
6-118815222-C-G		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
6-118815252-C-T		Inborn genetic diseases	Likely benign (Feb 27, 2024)
6-118815275-G-A		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
6-118815355-C-T			Benign (Mar 01, 2024)
6-118815367-G-A			Benign (Mar 01, 2024)
6-118815398-G-C		Inborn genetic diseases	Uncertain significance (Jan 17, 2023)
6-118815416-T-G		Inborn genetic diseases	Uncertain significance (May 09, 2023)
6-118815438-G-A		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
6-118815438-G-T			Benign (Mar 29, 2018)
6-118815455-G-A		Inborn genetic diseases	Uncertain significance (Oct 20, 2023)
6-118815479-T-C		Inborn genetic diseases	Uncertain significance (Mar 31, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCM9	protein_coding	protein_coding	ENST00000316316	12	121723

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.62e-14	0.948	125724	1	22	125747	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.45	493	592	0.832	0.0000308	7460
Missense in Polyphen		131	186.78	0.70137		2412
Synonymous	0.726	210	224	0.938	0.0000119	2240
Loss of Function	2.24	28	44.0	0.636	0.00000236	565

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000115	0.0000967
Middle Eastern	0.0000544	0.0000544
South Asian	0.000164	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the MCM8-MCM9 complex, a complex involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR) (PubMed:23401855). Required for DNA resection by the MRE11-RAD50- NBN/NBS1 (MRN) complex by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity (PubMed:26215093). Probably by regulating the localization of the MRN complex, indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs (PubMed:23401855). Acts as an helicase in DNA mismatch repair (MMR) following DNA replication errors to unwind the mismatch containing DNA strand (PubMed:26300262). In addition, recruits MLH1, a component of the MMR complex, to chromatin (PubMed:26300262). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:23401855). Probably by regulating HR, plays a key role during gametogenesis (By similarity). {ECO:0000250|UniProtKB:Q2KHI9, ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:26300262}.
• Disease: DISEASE: Ovarian dysgenesis 4 (ODG4) [MIM:616185]: A disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. {ECO:0000269|PubMed:25480036}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell Cycle (Consensus)

Haploinsufficiency Scores

• pHI: 0.249
• hipred: Y
• hipred_score: 0.672
• ghis: 0.603

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mcm9
• Phenotype: liver/biliary system phenotype; reproductive system phenotype; hematopoietic system phenotype; neoplasm; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: double-strand break repair via homologous recombination;DNA replication;cellular response to DNA damage stimulus;female gamete generation;DNA duplex unwinding;recombinational interstrand cross-link repair;mismatch repair involved in maintenance of fidelity involved in DNA-dependent DNA replication;protein localization to chromatin
• Cellular component: nucleus;chromosome;MCM8-MCM9 complex
• Molecular function: DNA binding;DNA helicase activity;chromatin binding;protein binding;ATP binding;enzyme binding;MutLbeta complex binding;MutSalpha complex binding;MutSbeta complex binding;protein-containing complex binding