Ophthalmological ciliopathies

Gene: MKS1

Green List (high evidence)

MKS1 (Meckel syndrome, type 1)
EnsemblGeneIds (GRCh38): ENSG00000011143
EnsemblGeneIds (GRCh37): ENSG00000011143
OMIM: 609883, Gene2Phenotype
MKS1 is in 27 panels

5 reviews

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Gene is green on the Bardet-Biedl Syndrome panel (version 1.53).
Created: 4 Aug 2016, 3:54 p.m.

Gabrielle Wheway (University of the West of England)

Green List (high evidence)

Along with MKS3 (TMEM67), one of the most common causes of Meckel-Gruber syndrome (MKS). Accounts for around 7% of all cases, and 70% of Finnish cases.

Mutations often affect splicing. Common Finn major mutation, 29bp deletion in intron 15 4bp from splice acceptor site. Predicted to affect splicing and cause frame-shifts which lead to nonsense-mediated decay and are therefore functional nulls.

Inherited in autosomal recessive homozygous and compound heterozygous pattern.

Skeletal involvement (the 'campomelic form') more common in MKS caused by MKS1 mutations. MKS1 mutations almost always associated with polydactyly and shortening and bowing of the long bones.

Single heterozygous mutations found in 5 BBS families, accompanied by homozygous mutations in BBS1 or BBS10. In these cases, MKS1 mutation considered a modifier. In two BBS families, compound heterozygous mutations have been found in MKS1 with no mutations in other known BBS genes. The mutations are; pC492W missense and F371del in one family and; Y461C and R534Q in another family; these are suggested to be hypomorphic mutations, suggested to cause milder BBS than null mutations causing MKS.
Created: 5 Jul 2016, 3:10 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Meckel-Gruber syndrome; Meckel syndrome; Bardet-Biedl syndrome; occipital encephalocele; polycystic kidneys; renal fibrosis; polydactyly


Mode of pathogenicity

Penny Clouston (Oxford)

Green List (high evidence)

On current diagnostic panel and positive families within patient cohort. Evidence from literature.
Created: 15 Mar 2016, 3:37 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Joubert syndrome; Meckel-Gruber syndrome


Variants in this GENE are reported as part of current diagnostic practice

Caroline Wright (Genomics England Curator)

Comment on list classification: Meckel syndrome
Created: 17 Dec 2015, 2:39 p.m.

Beth Hoskins (Great Ormond Street Hospital)

Red List (low evidence)

Mutations in this gene more commonly cause Meckel syndrome, only a single BBS case reported.
Created: 14 Oct 2015, 12:15 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal



History Filter Activity

8 Jul 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ivone Leong (Genomics England Curator)

gene: MKS1 was added gene: MKS1 was added to Ophthalmological ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing,Orphanet Mode of inheritance for gene: MKS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MKS1 were set to 26490104; 17437276; 18327255; 24886560; 16415886 Phenotypes for gene: MKS1 were set to occipital encephalocele; Joubert syndrome; Bardet-Biedl syndrome; Joubert syndrome 28; 249000; polydactyly; polycystic kidneys; Meckel-Gruber syndrome; Meckel syndrome; renal fibrosis