MKKS

MKKS centrosomal shuttling protein, the group of Chaperonins

Basic information

Region (hg38): 20:10401008-10434222

Previous symbols: [ "BBS6" ]

Links

ENSG00000125863 ∙ NCBI:8195 ∙ OMIM:604896 ∙ HGNC:7108 ∙ Uniprot:Q9NPJ1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• McKusick-Kaufman syndrome (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 6 (Strong), mode of inheritance: AR
• McKusick-Kaufman syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 6 (Strong), mode of inheritance: AR
• McKusick-Kaufman syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 6; McKusick-Kaufman syndrome	AR	Cardiovascular; Endocrine	McKusick-Kaufman syndrome can involve congenital cardiac anomalies, and awareness may allow early management; In Bardet-Biedl syndrome, medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Cardiovascular; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	14172277; 5694533; 5545396; 7262101; 7246610; 2681663; 2564737; 8209897; 10465109; 10973251; 11102925; 10802661; 11567139; 12837689; 15637713; 16104012; 20301537; 20301675; 36356613
Variants may modify severity of BBS and related disorders due to variants in other BBS-associated genes

ClinVar

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

• Bardet-Biedl syndrome;McKusick-Kaufman syndrome (203 variants)
• Bardet-Biedl syndrome 6 (100 variants)
• McKusick-Kaufman syndrome;Bardet-Biedl syndrome (80 variants)
• McKusick-Kaufman syndrome (67 variants)
• not provided (59 variants)
• McKusick-Kaufman syndrome;Bardet-Biedl syndrome 6 (31 variants)
• MKKS-related condition (29 variants)
• Inborn genetic diseases (26 variants)
• not specified (25 variants)
• Bardet-Biedl syndrome (21 variants)
• Bardet-Biedl syndrome 6;McKusick-Kaufman syndrome (16 variants)
• Retinal dystrophy (4 variants)
• Polycystic kidney disease;Multicystic kidney dysplasia (1 variants)
• Nephronophthisis (1 variants)
• MKKS-Related Disorders (1 variants)
• Bardet-biedl syndrome 2/6, digenic (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MKKS 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			1	60	2	63
missense	1	7	177	4	1	190
nonsense	7	12	2			21
start loss						0
frameshift	18	25	1			44
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2		1			3
splice region			3	2		5
non coding			24	20	9	53
Total	28	44	209	84	12

Highest pathogenic variant AF is 0.000105

Variants in MKKS

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

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

Position	Type	Phenotype	Significance	ClinVar
20-10404787-A-G		Bardet-Biedl syndrome 6 • McKusick-Kaufman syndrome	Uncertain significance (Jan 13, 2018)
20-10404812-C-T		Bardet-Biedl syndrome 6 • McKusick-Kaufman syndrome	Benign (Jan 12, 2018)
20-10404855-A-G		McKusick-Kaufman syndrome • Bardet-Biedl syndrome 6	Benign (Jan 13, 2018)
20-10405135-G-A		McKusick-Kaufman syndrome • Bardet-Biedl syndrome 6	Uncertain significance (Jan 13, 2018)
20-10405144-T-C		Bardet-Biedl syndrome 6 • McKusick-Kaufman syndrome	Uncertain significance (Jan 13, 2018)
20-10405201-C-A		not specified • Bardet-Biedl syndrome 6 • McKusick-Kaufman syndrome	Benign/Likely benign (Jan 20, 2021)
20-10405209-T-C		not specified • Bardet-Biedl syndrome 6 • McKusick-Kaufman syndrome	Benign/Likely benign (Jan 20, 2021)
20-10405226-T-C		McKusick-Kaufman syndrome • Bardet-Biedl syndrome 6	Uncertain significance (Jan 13, 2018)
20-10405237-T-C		MKKS-related disorder	Conflicting classifications of pathogenicity (Sep 16, 2019)
20-10405256-A-G		McKusick-Kaufman syndrome;Bardet-Biedl syndrome	Likely benign (Jan 24, 2023)
20-10405258-C-G		Bardet-Biedl syndrome 6 • McKusick-Kaufman syndrome	Uncertain significance (Jan 12, 2018)
20-10405260-T-A		MKKS-related disorder	Uncertain significance (Feb 22, 2024)
20-10405264-T-A		Inborn genetic diseases	Uncertain significance (May 23, 2023)
20-10405265-A-G		Bardet-Biedl syndrome;McKusick-Kaufman syndrome • McKusick-Kaufman syndrome;Bardet-Biedl syndrome 6	Likely benign (Oct 05, 2023)
20-10405268-A-G		McKusick-Kaufman syndrome;Bardet-Biedl syndrome	Likely benign (Jan 22, 2024)
20-10405268-A-T		not specified	Uncertain significance (Oct 25, 2021)
20-10405271-T-A		Bardet-Biedl syndrome;McKusick-Kaufman syndrome • MKKS-related disorder	Likely benign (Dec 10, 2023)
20-10405271-T-C		McKusick-Kaufman syndrome;Bardet-Biedl syndrome	Likely benign (May 21, 2023)
20-10405278-T-A		Bardet-Biedl syndrome;McKusick-Kaufman syndrome	Uncertain significance (Mar 10, 2020)
20-10405290-T-C		Bardet-Biedl syndrome 6 • McKusick-Kaufman syndrome • McKusick-Kaufman syndrome;Bardet-Biedl syndrome • MKKS-related disorder	Uncertain significance (Aug 16, 2023)
20-10405291-T-G		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
20-10405296-G-C		Bardet-Biedl syndrome;McKusick-Kaufman syndrome	Uncertain significance (Jun 13, 2022)
20-10405306-C-T		McKusick-Kaufman syndrome;Bardet-Biedl syndrome	Uncertain significance (Feb 04, 2022)
20-10405311-T-G		Bardet-Biedl syndrome;McKusick-Kaufman syndrome	Uncertain significance (Jul 10, 2023)
20-10405314-A-G		McKusick-Kaufman syndrome	Likely pathogenic (Mar 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MKKS	protein_coding	protein_coding	ENST00000347364	4	33214

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.13e-9	0.254	125681	0	65	125746	0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0520	288	286	1.01	0.0000138	3687
Missense in Polyphen		60	78.614	0.76322		1065
Synonymous	-1.51	129	109	1.18	0.00000537	1163
Loss of Function	0.648	15	18.0	0.835	8.32e-7	267

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000626	0.000626
Ashkenazi Jewish	0.00	0.00
East Asian	0.000490	0.000489
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000185	0.000185
Middle Eastern	0.000490	0.000489
South Asian	0.000555	0.000555
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis (PubMed:20080638). Plays a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). May play a role in protein processing in limb, cardiac and reproductive system development. May play a role in cytokinesis (PubMed:28753627). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:28753627}.
• Disease: DISEASE: McKusick-Kaufman syndrome (MKKS) [MIM:236700]: Autosomal recessive developmental disorder. It is characterized by hydrometrocolpos, postaxial polydactyly and congenital heart defects. {ECO:0000269|PubMed:10802661, ECO:0000269|PubMed:28753627}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bardet-Biedl syndrome 6 (BBS6) [MIM:605231]: 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:10973238, ECO:0000269|PubMed:10973251, ECO:0000269|PubMed:11179009, ECO:0000269|PubMed:11567139, ECO:0000269|PubMed:12107442, ECO:0000269|PubMed:12677556, ECO:0000269|PubMed:12920096, ECO:0000269|PubMed:15666242, ECO:0000269|PubMed:15731008, ECO:0000269|PubMed:15770229, ECO:0000269|PubMed:18094050, ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:21344540, ECO:0000269|PubMed:22152675, ECO:0000269|PubMed:26900326, ECO:0000269|PubMed:28753627, ECO:0000269|PubMed:28761321}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Integrated Lung Cancer Pathway;BBSome-mediated cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.306

Intolerance Scores

• loftool: 0.265
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.58

Haploinsufficiency Scores

• pHI: 0.468
• hipred: N
• hipred_score: 0.498
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.507

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mkks
• 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); 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); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; vision/eye 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); taste/olfaction phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: mkks
• Affected structure: pharyngeal arch 3-7
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: heart looping;protein folding;spermatid development;determination of left/right symmetry;heart development;visual perception;sensory perception of smell;gonad development;negative regulation of gene expression;artery smooth muscle contraction;striatum development;hippocampus development;cerebral cortex development;negative regulation of actin filament polymerization;melanosome transport;developmental process;negative regulation of GTPase activity;social behavior;negative regulation of appetite by leptin-mediated signaling pathway;positive regulation of multicellular organism growth;vasodilation;fat cell differentiation;photoreceptor cell maintenance;negative regulation of blood pressure;intracellular transport;brain morphogenesis;detection of mechanical stimulus involved in sensory perception of sound;chaperone-mediated protein complex assembly;cartilage development;regulation of stress fiber assembly;pigment granule aggregation in cell center;convergent extension involved in gastrulation;cilium assembly;regulation of cilium beat frequency involved in ciliary motility;face development;non-motile cilium assembly
• Cellular component: nucleus;cytoplasm;centrosome;cytosol;motile cilium;ciliary basal body;kinociliary basal body
• Molecular function: RNA polymerase II repressing transcription factor binding;protein binding;ATP binding;unfolded protein binding