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

ENSG00000011143 ∙ NCBI:54903 ∙ OMIM:609883 ∙ HGNC:7121 ∙ Uniprot:Q9NXB0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

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 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	183	1	192
missense	4	2	279	1		286
nonsense	20	24	1			45
start loss	2	1				3
frameshift	21	30	4			55
inframe indel	2	2	6			10
splice donor/acceptor (+/-2bp)	6	41	1			48
splice region	1	1	21	55	1	79
non coding	1	2	25	168	21	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)
17-58205485-A-C		Bardet-Biedl syndrome 13 • Meckel syndrome, type 1	Uncertain significance (Jan 12, 2018)
17-58205607-G-C		Bardet-Biedl syndrome 13 • Meckel syndrome, type 1	Benign/Likely benign (Jan 13, 2018)
17-58205610-G-A		Bardet-Biedl syndrome 13 • Meckel syndrome, type 1	Uncertain significance (Jan 13, 2018)
17-58205664-C-T		Bardet-Biedl syndrome 13 • Meckel syndrome, type 1	Uncertain significance (Jan 12, 2018)
17-58205665-G-A		Bardet-Biedl syndrome 13 • Meckel syndrome, type 1	Benign (Jan 13, 2018)
17-58205698-T-C		Meckel syndrome, type 1 • Bardet-Biedl syndrome 13	Uncertain significance (Jan 12, 2018)
17-58205727-AC-A			Benign (May 14, 2021)
17-58205757-C-A		Bardet-Biedl syndrome 13 • Meckel syndrome, type 1	Conflicting classifications of pathogenicity (Feb 01, 2025)
17-58205945-G-A		Meckel syndrome, type 1 • Bardet-Biedl syndrome 13	Conflicting classifications of pathogenicity (Jan 01, 2023)
17-58205982-C-T		MKS1-related disorder	Likely benign (Dec 18, 2020)
17-58205983-G-A		MKS1-related disorder	Likely benign (Apr 30, 2019)
17-58206003-C-T		MKS1-related disorder	Uncertain significance (Feb 14, 2024)
17-58206004-G-A		Bardet-Biedl syndrome 13 • Meckel syndrome, type 1 • MKS1-related disorder	Benign (Jun 16, 2018)
17-58206009-G-T		MKS1-related disorder	Uncertain significance (Mar 22, 2023)
17-58206016-G-C		MKS1-related disorder	Uncertain significance (Jun 27, 2024)
17-58206021-C-G		MKS1-related disorder	Likely benign (Apr 30, 2019)
17-58206030-G-T		Meckel syndrome, type 1 • Bardet-Biedl syndrome 13 • MKS1-related disorder	Uncertain significance (Jan 13, 2018)
17-58206036-C-T		MKS1-related disorder	Uncertain significance (Sep 16, 2024)
17-58206040-AT-A			Benign/Likely benign (Jun 01, 2024)
17-58206053-G-T		MKS1-related disorder	Uncertain significance (Jun 27, 2023)
17-58206081-A-G		Familial aplasia of the vermis;Meckel-Gruber syndrome • not specified • MKS1-related disorder	Uncertain significance (Dec 19, 2022)
17-58206082-G-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Feb 19, 2023)
17-58206085-G-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Oct 29, 2024)
17-58206088-C-A		Familial aplasia of the vermis;Meckel-Gruber syndrome	Conflicting classifications of pathogenicity (Feb 17, 2024)

GnomAD

Source: gnomAD

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: 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

	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