MKKS McKusick-Kaufman syndrome [Homo sapiens (human)] - Gene

Summary

Official Symbol: MKKSprovided by HGNC
Official Full Name: McKusick-Kaufman syndromeprovided by HGNC
Primary source: HGNC:HGNC:7108
See related: Ensembl:ENSG00000125863 MIM:604896
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: KMS; MKS; BBS6; HMCS
Summary: This gene encodes a protein which shares sequence similarity with other members of the type II chaperonin family. The encoded protein is a centrosome-shuttling protein and plays an important role in cytokinesis. This protein also interacts with other type II chaperonin members to form a complex known as the BBSome, which involves ciliary membrane biogenesis. This protein is encoded by a downstream open reading frame (dORF). Several upstream open reading frames (uORFs) have been identified, which repress the translation of the dORF, and two of which can encode small mitochondrial membrane proteins. Mutations in this gene have been observed in patients with Bardet-Biedl syndrome type 6, also known as McKusick-Kaufman syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]
Expression: Ubiquitous expression in kidney (RPKM 13.4), testis (RPKM 12.8) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 20p12.2

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
109.20190607	current	GRCh38.p13 (GCF_000001405.39)	20	NC_000020.11 (10401009..10434239, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (10385428..10414887, complement)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Two novel mutations and three previously reported variants, identified in the present study, further extend the body of evidence implicating BBS6, BBS7, BBS8, and BBS10 in causing Bardet-Biedl Syndrome.
Title: Sequence variants in four genes underlying Bardet-Biedl syndrome in consanguineous families.
found compound heterozygous variants (c.1192C>T, p.Q398* and c.1175C>T, p.T392M) in MKKS in both the siblings, and these were likely to be pathogenic variants
Title: Whole-exome sequencing identified compound heterozygous variants in MMKS in a Chinese pedigree with Bardet-Biedl syndrome.
We identified a novel H395R substitution in MKKS/BBS6 that results in a unique phenotype of only retinitis pigmentosa and polydactyly.
Title: A novel H395R mutation in MKKS/BBS6 causes retinitis pigmentosa and polydactyly without other findings of Bardet-Biedl or McKusick-Kaufman syndrome.
we report here, for the first time, in Indian population, a novel, different profile of mutations in BBS genes (BBS3, BBS9, BBS10 and BBS2) compared to worldwide (BBS1 and 10) reports.
Title: Mutation spectrum in BBS genes guided by homozygosity mapping in an Indian cohort.
Novel mutation (c.1272+1G>A) in BBS6 found in Tunisian families with Bardet-Biedl syndrome.
Title: Clinical and genetic characterization of Bardet-Biedl syndrome in Tunisia: defining a strategy for molecular diagnosis.
Findings indicate that Bbs proteins play a central role in the regulation of the actin cytoskeleton and control the cilia length through alteration of RhoA levels.
Title: Bardet-Biedl syndrome proteins control the cilia length through regulation of actin polymerization.
Three uORFs (uMKKS0, uMKKS1 and uMKKS2) are reported, and they can repress the translation of the downstream MKKS ORF. uMKKS1 and uMKKS2 are highly conserved in mammals and they encode two different mitochondrial membrane proteins respectively.
Title: Translational repression of the McKusick-Kaufman syndrome transcript by unique upstream open reading frames encoding mitochondrial proteins with alternative polyadenylation sites.
Observational study of genetic testing. (HuGE Navigator)
Title: Simultaneous mutation detection in 90 retinal disease genes in multiple patients using a custom-designed 300-kb retinal resequencing chip.
Using sequence analysis, the role of BBS6, 10 and 12 was assessed in a Bardet-Biedl syndrome patient population comprising 93 cases from 74 families.
Title: Mutations in chaperonin-like BBS genes are a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.

Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Bardet-Biedl syndrome MedGen: C0752166 GeneReviews: Bardet-Biedl Syndrome	not available
Bardet-Biedl syndrome 6 MedGen: C1858054 OMIM: 605231 GeneReviews: Bardet-Biedl Syndrome	not available
McKusick Kaufman syndrome MedGen: C0948368 OMIM: 236700 GeneReviews: McKusick-Kaufman Syndrome	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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BBSome-mediated cargo-targeting to cilium, organism-specific biosystem (from REACTOME)
BBSome-mediated cargo-targeting to cilium, organism-specific biosystemThe BBSome is a stable complex consisting of 7 Bardet-Biedl proteins (BBS1, 2, 4, 5, 7, 8 and 9) and BBIP10 that has roles in promoting IFT and trafficking proteins to the cilum (Blacque et al, 2004;...
Cargo trafficking to the periciliary membrane, organism-specific biosystem (from REACTOME)
Cargo trafficking to the periciliary membrane, organism-specific biosystemProteomic studies suggest that the cilium is home to approximately a thousand proteins, and has a unique protein and lipid make up relative to the bulk cytoplasm and plasma membrane (Pazour et al, 20...
Cilium Assembly, organism-specific biosystem (from REACTOME)
Cilium Assembly, organism-specific biosystemCilia are membrane covered organelles that extend from the surface of eukaryotic cells. Cilia may be motile, such as respiratory cilia) or non-motile (such as the primary cilium) and are distinguishe...
Organelle biogenesis and maintenance, organism-specific biosystem (from REACTOME)
Organelle biogenesis and maintenance, organism-specific biosystemThis module describes the biogenesis of organelles. Organelles are subcellular structures of distinctive morphology and function. The organelles of human cells include: mitochondria, endoplasmic reti...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-R67339 (e-PCR)
- UniSTS:34376

MKKS__7396 (e-PCR)
- UniSTS:466338

RH46023 (e-PCR)
- UniSTS:52916

G60203 (e-PCR)
- UniSTS:137462

Homology

Homologs of the MKKS gene: The MKKS gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 279 organisms have orthologs with human gene MKKS
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
RNA polymerase II repressing transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
unfolded protein binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
artery smooth muscle contraction	IEA Inferred from Electronic Annotation more info
brain morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
cartilage development	IEA Inferred from Electronic Annotation more info
cerebral cortex development	ISS Inferred from Sequence or Structural Similarity more info
chaperone-mediated protein complex assembly	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cilium assembly	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cilium assembly	IMP Inferred from Mutant Phenotype more info	PubMed
cilium assembly	ISS Inferred from Sequence or Structural Similarity more info
convergent extension involved in gastrulation	ISS Inferred from Sequence or Structural Similarity more info
detection of mechanical stimulus involved in sensory perception of sound	ISS Inferred from Sequence or Structural Similarity more info
determination of left/right symmetry	ISS Inferred from Sequence or Structural Similarity more info
developmental process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
face development	IEA Inferred from Electronic Annotation more info
fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
gonad development	TAS Traceable Author Statement more info	PubMed
heart development	TAS Traceable Author Statement more info	PubMed
heart looping	ISS Inferred from Sequence or Structural Similarity more info
hippocampus development	ISS Inferred from Sequence or Structural Similarity more info
intracellular transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
intracellular transport	ISS Inferred from Sequence or Structural Similarity more info
melanosome transport	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of GTPase activity	IEA Inferred from Electronic Annotation more info
negative regulation of actin filament polymerization	IEA Inferred from Electronic Annotation more info
negative regulation of appetite by leptin-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of blood pressure	IEA Inferred from Electronic Annotation more info
negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
non-motile cilium assembly	IEA Inferred from Electronic Annotation more info
photoreceptor cell maintenance	ISS Inferred from Sequence or Structural Similarity more info
pigment granule aggregation in cell center	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of multicellular organism growth	IEA Inferred from Electronic Annotation more info
protein folding	IEA Inferred from Electronic Annotation more info
regulation of cilium beat frequency involved in ciliary motility	ISS Inferred from Sequence or Structural Similarity more info
regulation of stress fiber assembly	IEA Inferred from Electronic Annotation more info
sensory perception of smell	ISS Inferred from Sequence or Structural Similarity more info
social behavior	ISS Inferred from Sequence or Structural Similarity more info
spermatid development	ISS Inferred from Sequence or Structural Similarity more info
striatum development	ISS Inferred from Sequence or Structural Similarity more info
vasodilation	IEA Inferred from Electronic Annotation more info
visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
centrosome	IDA Inferred from Direct Assay more info
ciliary basal body	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IEA Inferred from Electronic Annotation more info
kinociliary basal body	IBA Inferred from Biological aspect of Ancestor more info	PubMed
motile cilium	ISS Inferred from Sequence or Structural Similarity more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin

Names: Bardet-Biedl syndrome 6 protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009109.2 RefSeqGene

Range

4980..34439

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_018848.3 → NP_061336.1 McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin

See identical proteins and their annotated locations for NP_061336.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1 and 2 encode the same protein.

Source sequence(s)

AF221993, AK296439, AL034430

Consensus CDS

CCDS13111.1

UniProtKB/Swiss-Prot

Q9NPJ1

UniProtKB/TrEMBL

B7Z3W9

Related

ENSP00000382008.2, ENST00000399054.6

Conserved Domains (2) summary

pfam00118
Location:29 → 569

Cpn60_TCP1; TCP-1/cpn60 chaperonin family

cl02777
Location:32 → 476

chaperonin_like; chaperonin_like superfamily. Chaperonins are involved in productive folding of proteins. They share a common general morphology, a double toroid of 2 stacked rings, each composed of 7-9 subunits. There are 2 main chaperonin groups. The symmetry of type I ...
NM_170784.2 → NP_740754.1 McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin

See identical proteins and their annotated locations for NP_740754.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same protein.

Source sequence(s)

AF221992, AK296439, AL034430, DA209180

Consensus CDS

CCDS13111.1

UniProtKB/Swiss-Prot

Q9NPJ1

UniProtKB/TrEMBL

B7Z3W9

Related

ENSP00000246062.4, ENST00000347364.7

Conserved Domains (2) summary

pfam00118
Location:29 → 569

Cpn60_TCP1; TCP-1/cpn60 chaperonin family

cl02777
Location:32 → 476

chaperonin_like; chaperonin_like superfamily. Chaperonins are involved in productive folding of proteins. They share a common general morphology, a double toroid of 2 stacked rings, each composed of 7-9 subunits. There are 2 main chaperonin groups. The symmetry of type I ...

RNA

NR_072977.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an internal exon, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AK296439, AL034430