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
Phenotypes
GenCC
Source:
- Meckel syndrome, type 1 (Definitive), mode of inheritance: AR
- Bardet-Biedl syndrome 13 (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:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Bardet-Biedl syndrome 13 | AR | Endocrine | Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial | Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal | 6486167; 16415886; 17377820; 17935508; 18327255; 19515853; 20301537; 24608809; 24886560; 36356613 |
ClinVar
This is a list of variants' phenotypes submitted to
- Joubert_syndrome (841 variants)
- Meckel-Gruber_syndrome (838 variants)
- Meckel_syndrome,_type_1 (323 variants)
- Bardet-Biedl_syndrome_13 (240 variants)
- MKS1-related_disorder (216 variants)
- not_provided (189 variants)
- Joubert_syndrome_28 (188 variants)
- Inborn_genetic_diseases (76 variants)
- not_specified (46 variants)
- Bardet-Biedl_syndrome (7 variants)
- Retinal_dystrophy (4 variants)
- Polydactyly (3 variants)
- Optic_atrophy (3 variants)
- Hypotonia (2 variants)
- Nystagmus (2 variants)
- Leber_congenital_amaurosis_6 (1 variants)
- Peripheral_neuropathy (1 variants)
- Microcephaly (1 variants)
- Chronic_kidney_disease (1 variants)
- Joubert_syndrome_and_related_disorders (1 variants)
- Multicystic_kidney_dysplasia (1 variants)
- Limb_undergrowth (1 variants)
- Global_developmental_delay (1 variants)
- Polycystic_kidney_disease (1 variants)
- Spastic_ataxia (1 variants)
- Rotary_nystagmus (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. These statistics are base on transcript: NM_000017777.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 20 | 233 | 255 | |||
| missense | 342 | 16 | 372 | |||
| nonsense | 20 | 29 | 50 | |||
| start loss | 2 | 1 | 3 | |||
| frameshift | 29 | 32 | 65 | |||
| splice donor/acceptor (+/-2bp) | 43 | 50 | ||||
| Total | 64 | 115 | 367 | 249 | 0 |
Highest pathogenic variant AF is 0.0011076444
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MKS1 | protein_coding | protein_coding | ENST00000393119 | 18 | 14164 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.38e-16 | 0.244 | 124690 | 0 | 120 | 124810 | 0.000481 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.492 | 296 | 321 | 0.923 | 0.0000212 | 3629 |
| Missense in Polyphen | 70 | 82.065 | 0.85298 | 904 | ||
| Synonymous | 0.0624 | 123 | 124 | 0.993 | 0.00000799 | 1084 |
| Loss of Function | 1.35 | 29 | 37.9 | 0.764 | 0.00000228 | 405 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000706 | 0.000706 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00173 | 0.00173 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000354 | 0.000353 |
| Middle Eastern | 0.00173 | 0.00173 |
| South Asian | 0.00101 | 0.00101 |
| Other | 0.000165 | 0.000165 |
dbNSFP
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
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