MKS1

MKS transition zone complex subunit 1, the group of MKS complex|B9 domain containing

Basic information

Region (hg38): 17:58205441-58219605

Previous symbols: [ "MKS" ]

Links

ENSG00000011143NCBI:54903OMIM:609883HGNC:7121Uniprot:Q9NXB0AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Meckel syndrome, type 1 (Definitive), mode of inheritance: AR
  • Bardet-Biedl syndrome 13 (Strong), mode of inheritance: AR
  • Meckel syndrome (Supportive), mode of inheritance: AR
  • Joubert syndrome (Supportive), mode of inheritance: AR
  • Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
  • Joubert syndrome with ocular defect (Supportive), mode of inheritance: AR
  • Meckel syndrome, type 1 (Strong), mode of inheritance: AR
  • Joubert syndrome 28 (Strong), mode of inheritance: AR
  • Bardet-Biedl syndrome 13 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Bardet-Biedl syndrome 13AREndocrineMedical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficialCraniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal6486167; 16415886; 17377820; 17935508; 18327255; 19515853; 20301537; 24608809; 24886560; 36356613

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MKS1 gene.

  • Familial aplasia of the vermis;Meckel-Gruber syndrome (24 variants)
  • Meckel-Gruber syndrome;Familial aplasia of the vermis (21 variants)
  • Familial aplasia of the vermis (8 variants)
  • not provided (6 variants)
  • Meckel syndrome, type 1 (4 variants)
  • Bardet-Biedl syndrome 13 (3 variants)
  • Meckel-Gruber syndrome (2 variants)
  • MKS1-related disorder (2 variants)
  • Polydactyly;Hypotonia;Nystagmus (1 variants)
  • Bardet-Biedl syndrome 13;Meckel syndrome, type 1;Joubert syndrome 28 (1 variants)
  • Joubert syndrome 28 (1 variants)
  • Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MKS1 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
8
clinvar
183
clinvar
1
clinvar
192
missense
4
clinvar
2
clinvar
279
clinvar
1
clinvar
286
nonsense
20
clinvar
24
clinvar
1
clinvar
45
start loss
2
clinvar
1
clinvar
3
frameshift
21
clinvar
30
clinvar
4
clinvar
55
inframe indel
2
clinvar
2
clinvar
6
clinvar
10
splice donor/acceptor (+/-2bp)
6
clinvar
41
clinvar
1
clinvar
48
splice region
1
1
21
55
1
79
non coding
1
clinvar
2
clinvar
25
clinvar
168
clinvar
21
clinvar
217
Total 56 102 324 352 22

Highest pathogenic variant AF is 0.00120

Variants in MKS1

This is a list of pathogenic ClinVar variants found in the MKS1 region.

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

Position Type Phenotype Significance ClinVar
17-58205476-A-C Meckel syndrome, type 1 • Bardet-Biedl syndrome 13 Uncertain significance (Jan 13, 2018)891097
17-58205485-A-C Bardet-Biedl syndrome 13 • Meckel syndrome, type 1 Uncertain significance (Jan 12, 2018)891098
17-58205607-G-C Bardet-Biedl syndrome 13 • Meckel syndrome, type 1 Benign/Likely benign (Jan 13, 2018)892306
17-58205610-G-A Bardet-Biedl syndrome 13 • Meckel syndrome, type 1 Uncertain significance (Jan 13, 2018)324153
17-58205664-C-T Bardet-Biedl syndrome 13 • Meckel syndrome, type 1 Uncertain significance (Jan 12, 2018)892307
17-58205665-G-A Bardet-Biedl syndrome 13 • Meckel syndrome, type 1 Benign (Jan 13, 2018)324154
17-58205698-T-C Meckel syndrome, type 1 • Bardet-Biedl syndrome 13 Uncertain significance (Jan 12, 2018)324155
17-58205727-AC-A Benign (May 14, 2021)1277626
17-58205757-C-A Bardet-Biedl syndrome 13 • Meckel syndrome, type 1 Conflicting classifications of pathogenicity (Feb 01, 2025)324156
17-58205945-G-A Meckel syndrome, type 1 • Bardet-Biedl syndrome 13 Conflicting classifications of pathogenicity (Jan 01, 2023)888910
17-58205982-C-T MKS1-related disorder Likely benign (Dec 18, 2020)3358438
17-58205983-G-A MKS1-related disorder Likely benign (Apr 30, 2019)3044387
17-58206003-C-T MKS1-related disorder Uncertain significance (Feb 14, 2024)3054692
17-58206004-G-A Bardet-Biedl syndrome 13 • Meckel syndrome, type 1 • MKS1-related disorder Benign (Jun 16, 2018)324157
17-58206009-G-T MKS1-related disorder Uncertain significance (Mar 22, 2023)2632071
17-58206016-G-C MKS1-related disorder Uncertain significance (Jun 27, 2024)3347589
17-58206021-C-G MKS1-related disorder Likely benign (Apr 30, 2019)3037883
17-58206030-G-T Meckel syndrome, type 1 • Bardet-Biedl syndrome 13 • MKS1-related disorder Uncertain significance (Jan 13, 2018)890608
17-58206036-C-T MKS1-related disorder Uncertain significance (Sep 16, 2024)2631936
17-58206040-AT-A Benign/Likely benign (Jun 01, 2024)1187069
17-58206053-G-T MKS1-related disorder Uncertain significance (Jun 27, 2023)2629384
17-58206081-A-G Familial aplasia of the vermis;Meckel-Gruber syndrome • not specified • MKS1-related disorder Uncertain significance (Dec 19, 2022)1501927
17-58206082-G-A Meckel-Gruber syndrome;Familial aplasia of the vermis Likely benign (Feb 19, 2023)1654920
17-58206085-G-A Meckel-Gruber syndrome;Familial aplasia of the vermis Likely benign (Oct 29, 2024)1131427
17-58206088-C-A Meckel-Gruber syndrome;Familial aplasia of the vermis Conflicting classifications of pathogenicity (Feb 17, 2024)500044

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
MKS1protein_codingprotein_codingENST00000393119 1814164
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
3.38e-160.24412469001201248100.000481
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.4922963210.9230.00002123629
Missense in Polyphen7082.0650.85298904
Synonymous0.06241231240.9930.000007991084
Loss of Function1.352937.90.7640.00000228405

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0007060.000706
Ashkenazi Jewish0.000.00
East Asian0.001730.00173
Finnish0.000.00
European (Non-Finnish)0.0003540.000353
Middle Eastern0.001730.00173
South Asian0.001010.00101
Other0.0001650.000165

dbNSFP

Source: dbNSFP

Function
FUNCTION: Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Involved in centrosome migration to the apical cell surface during early ciliogenesis. Required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication. Required for cell branching morphology. {ECO:0000269|PubMed:17185389, ECO:0000269|PubMed:19515853, ECO:0000269|PubMed:26490104}.;
Disease
DISEASE: Meckel syndrome 1 (MKS1) [MIM:249000]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:16415886, ECO:0000269|PubMed:19466712, ECO:0000269|PubMed:26490104}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bardet-Biedl syndrome 13 (BBS13) [MIM:615990]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:18327255}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Joubert syndrome 28 (JBTS28) [MIM:617121]: A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS28 inheritance is autosomal recessive. {ECO:0000269|PubMed:24886560}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Ectoderm Differentiation;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

pRec
0.357

Intolerance Scores

loftool
0.974
rvis_EVS
-0.04
rvis_percentile_EVS
50.45

Haploinsufficiency Scores

pHI
0.0678
hipred
N
hipred_score
0.229
ghis
0.557

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.891

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Mks1
Phenotype
endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype;

Zebrafish Information Network

Gene name
mks1
Affected structure
whole organism
Phenotype tag
abnormal
Phenotype quality
decreased life span

Gene ontology

Biological process
neural tube closure;smoothened signaling pathway involved in regulation of secondary heart field cardioblast proliferation;determination of left/right symmetry;epithelial structure maintenance;embryonic digit morphogenesis;motile cilium assembly;embryonic skeletal system development;branching morphogenesis of an epithelial tube;inner ear receptor cell stereocilium organization;cilium assembly;head development;cardiac septum morphogenesis;regulation of canonical Wnt signaling pathway;common bile duct development;ciliary basal body-plasma membrane docking;regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning;non-motile cilium assembly;embryonic brain development;regulation of Wnt signaling pathway, planar cell polarity pathway
Cellular component
cytoplasm;centrosome;centriole;cytosol;membrane;MKS complex;ciliary basal body
Molecular function
protein binding