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Inherited polyposis and early onset colorectal cancer - germline testing

Gene: MSH3

Amber List (moderate evidence)
MSH3 (mutS homolog 3)
EnsemblGeneIds (GRCh38): ENSG00000113318
EnsemblGeneIds (GRCh37): ENSG00000113318
OMIM: 600887, Gene2Phenotype
MSH3 is in 2 panels

5 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now sufficient cases to promote this gene to green, following GMS review.
Created: 21 Oct 2025, 10:34 p.m. | Last Modified: 21 Oct 2025, 10:34 p.m.
Panel Version: 3.8
In OMIM MSH3 is associated with Endometrial carcinoma, somatic, OMIM:608089 and Familial adenomatous polyposis 4, OMIM:617100 (AR) (accessed 21st October 2025)

MSH3 has a definitive association with familial adenomatous polyposis 4, MONDO:0044300 (last curated May 24, 2024).

As reported by ClinGen: 19 variants (nonsense, frameshift, large deletion, splicing, missense) have been reported in 10 probands in 6 publications (PMIDs 27476653, 37597744, 35675019, 38243056, 34250384, 37402566). This is also supported by expression studies, in vitro functional assays, and animal models (PMIDs: 18922920, 24013230, 10706084, 27476653).
The mechanism of pathogenicity is known to be loss of function.
Created: 21 Oct 2025, 10:32 p.m. | Last Modified: 21 Oct 2025, 10:33 p.m.
Panel Version: 3.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Familial adenomatous polyposis 4, OMIM:617100; familial adenomatous polyposis 4, MONDO:0044300

Publications

Created: 21 Oct 2025, 10:32 p.m.
Last Modified: 21 Oct 2025, 10:33 p.m.
Panel version: 3.5

Arina Puzriakova (Genomics England Curator)

Comment on phenotypes: This gene is also associated with Endometrial carcinoma, somatic (MIM# 608089)
Created: 8 Mar 2021, 11:01 a.m. | Last Modified: 8 Mar 2021, 11:01 a.m.
Panel Version: 1.21
Created: 8 Mar 2021, 11:01 a.m.
Last Modified: 8 Mar 2021, 11:01 a.m.
Panel version: 1.21

Ivone Leong (Genomics England Curator)

Comment on mode of inheritance: Corrected the MOI. Changed Monoallelic to Biallelic.
Created: 5 Aug 2019, 10:21 a.m. | Last Modified: 5 Aug 2019, 10:21 a.m.
Panel Version: 0.51
Comment on list classification: As discussed in the GMS Inherited Cancer Specialist Test Group webex call 31st Jan 2019: The Specialist Test Group agreed that this gene should be rated amber as cases in this gene is rare.
Created: 1 Feb 2019, 10:06 a.m.
Created: 1 Feb 2019, 10:06 a.m.

Panel version: 0.42

Rachel Robinson (Leeds Genetics Laboratory)

Green List (high evidence)

Publications

Created: 30 Jan 2019, 9:44 a.m.

Panel version: 0.3

Treena Cranston (Oxford)

Red List (low evidence)

Discussed with Prof Ian Tomlinson. To be added to PanelApp as there has been a recent proposal that it may be asssociated with autosomal recessive polyposis/CRC. Not yet published hence low evidence.
Created: 20 Jul 2016, 7:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 20 Jul 2016, 7:09 a.m.

Panel version: Imported from Inherited colorectal cancer (with or without polyposis) panel version Imported from "Familial colon cancer" panel version 1.2

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • Familial adenomatous polyposis 4, OMIM:617100
  • familial adenomatous polyposis 4, MONDO:0044300
Tags
Q3_25_promote_green
OMIM
600887
Clinvar variants
Variants in MSH3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

21 Oct 2025, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: msh3 has been classified as Amber List (Moderate Evidence).

21 Oct 2025, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: MSH3 were changed from Familial adenomatous polyposis 4, OMIM:617100 to Familial adenomatous polyposis 4, OMIM:617100; familial adenomatous polyposis 4, MONDO:0044300

21 Oct 2025, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MSH3 were set to 27476653

21 Oct 2025, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q3_25_promote_green tag was added to gene: MSH3.

8 Mar 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: MSH3 were set to

8 Mar 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: MSH3 were changed from to Familial adenomatous polyposis 4, OMIM:617100

5 Aug 2019, Gel status: 2

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: MSH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal

1 Feb 2019, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: msh3 has been classified as Amber List (Moderate Evidence).

30 Jan 2019, Gel status: 3

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: MSH3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

30 Jan 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: msh3 has been classified as Green List (High Evidence).

30 Jan 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Ivone Leong (Genomics England Curator)

gene: MSH3 was added gene: MSH3 was added to Inherited polyposis. Sources: NHS GMS Mode of inheritance for gene: MSH3 was set to