MSH5

mutS homolog 5, the group of MutS homologs

Basic information

Region (hg38): 6:31739676-31762676

Links

ENSG00000204410 ∙ NCBI:4439 ∙ OMIM:603382 ∙ HGNC:7328 ∙ Uniprot:O43196 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 74 (Strong), mode of inheritance: AR
• premature ovarian failure 13 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Premature ovarian failure 13	AR	Obstetric	Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	Endocrine; Genitourinary; Obstetric	28175301; 34755185

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MSH5 gene.

• Inborn genetic diseases (26 variants)
• not provided (5 variants)
• Spermatogenic failure 74 (4 variants)
• not specified (3 variants)
• Non-obstructive azoospermia (3 variants)
• MSH5-related condition (1 variants)
• Genetic non-acquired premature ovarian failure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MSH5 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	3
missense		1	27	2	2	32
nonsense		1				1
start loss						0
frameshift	2					2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	2	2	27	2	5

Highest pathogenic variant AF is 0.0000197

Variants in MSH5

This is a list of pathogenic ClinVar variants found in the MSH5 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-31740525-C-A		not specified	Uncertain significance (Jun 28, 2023)
6-31740537-T-TC		Non-obstructive azoospermia • Spermatogenic failure 74	Pathogenic (May 26, 2020)
6-31740551-C-T		not specified • MSH5-related disorder	Benign (Jul 24, 2019)
6-31741167-A-G		not specified	Uncertain significance (Jan 23, 2023)
6-31741212-A-G		not specified	Uncertain significance (May 24, 2023)
6-31741261-C-G		not specified	Uncertain significance (Oct 27, 2021)
6-31741268-C-T		MSH5-related disorder	Benign (Oct 17, 2019)
6-31741276-T-G		MSH5-related disorder	Likely benign (Jun 14, 2019)
6-31742911-G-A		MSH5-related disorder	Benign/Likely benign (Sep 24, 2019)
6-31743119-C-G		not specified	Uncertain significance (Nov 18, 2022)
6-31743949-T-C		not specified	Uncertain significance (Jan 03, 2024)
6-31743963-A-G		not specified	Uncertain significance (Mar 01, 2024)
6-31744014-T-C		not specified	Uncertain significance (Jan 10, 2022)
6-31744026-G-A		Azoospermia	Pathogenic (Dec 20, 2021)
6-31744133-C-T		MSH5-related disorder	Likely benign (Sep 12, 2019)
6-31744194-G-A		Premature ovarian failure 13	Uncertain significance (Mar 26, 2024)
6-31744226-C-G		not specified	Uncertain significance (Dec 15, 2022)
6-31744238-G-A		not specified	Uncertain significance (Jun 06, 2023)
6-31744560-A-G		not specified	Likely benign (Jan 09, 2024)
6-31753314-C-T		Genetic non-acquired premature ovarian failure	Likely pathogenic (Oct 01, 2019)
6-31753364-G-T		not specified	Uncertain significance (Nov 30, 2021)
6-31753437-C-T		not specified	Uncertain significance (Feb 23, 2023)
6-31753579-C-T		Non-obstructive azoospermia • Spermatogenic failure 74	Likely pathogenic (May 09, 2021)
6-31753596-C-A		not specified	Uncertain significance (Oct 14, 2023)
6-31753609-G-A		not specified	Uncertain significance (Aug 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MSH5	protein_coding	protein_coding	ENST00000375703	24	24898

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.20e-11	1.00	125550	0	198	125748	0.000788

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.80	367	478	0.768	0.0000270	5432
Missense in Polyphen		87	128.74	0.6758		1470
Synonymous	2.22	146	184	0.792	0.0000104	1676
Loss of Function	3.30	26	51.6	0.504	0.00000312	529

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00187	0.00181
Ashkenazi Jewish	0.000509	0.000496
East Asian	0.000546	0.000544
Finnish	0.000281	0.000277
European (Non-Finnish)	0.00111	0.00109
Middle Eastern	0.000546	0.000544
South Asian	0.000361	0.000359
Other	0.000494	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in DNA mismatch repair and meiotic recombination processes. Facilitates crossovers between homologs during meiosis (By similarity). {ECO:0000250}.
• Pathway: Ovarian Infertility Genes (Consensus)

Intolerance Scores

• loftool: 0.0416
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.57

Haploinsufficiency Scores

• pHI: 0.179
• hipred: N
• hipred_score: 0.403
• ghis: 0.525

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• 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: Msh5
• Phenotype: reproductive system phenotype; neoplasm; growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype

Gene ontology

• Biological process: mismatch repair;reciprocal meiotic recombination;homologous chromosome segregation;chiasma assembly
• Cellular component: mismatch repair complex
• Molecular function: damaged DNA binding;protein binding;ATP binding;DNA-dependent ATPase activity;guanine/thymine mispair binding;single thymine insertion binding