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The search for the genetic causes of lymphedema has discovered yet another gene. This brings our website total now to eight (8) specific genes that cause one type of lymphedema syndrome or another.
In an article release January of 2012, researchers at St. George’s University of London announced the discovery that mutations in KIF11 causes the autosomal-dominant Lymphedema Microcephaly, Chorioretinopathy syndrome. The article was originally published by the American Society of Human Genetics.
February 1, 2012
Related Terms: lymphedema, Mutations, autosomal-dominant, microcephaly, chorioretinopathy, congenital, KIF11, proband, EG5, homotetramer kinesin motor, retinal structures, lymphatic structures, MLCRD, lymphoscintigraphy, chromosomes, Kinesin superfamily proteins, KIFs
This study of this particular gene is quite young and thus obtaining information was somewhat problematic, but here is what I could find and links to other helpful sites.
Aliases & Descriptions
kinesin family member 111 2 Thyroid receptor-interacting protein 52 3
TRIP51 2 3 EG5
KNSL12 3 5 TRIP-52
HKSP1 2 TR-interacting protein 5
kinesin-like 11 2 Eg51
Kinesin-like protein 12 3 OTTHUMP000000200992
Kinesin-like spindle protein HKSP2 3 kinesin-like protein KIF112
Kinesin-related motor protein Eg52 3 thyroid receptor interacting protein 52
External Ids: HGNC: 6388
Entrez Gene: 38322
Ensembl: ENSG000001381607 OMIM: 1487605
KIF11 kinesin family member 11 [ Homo sapiens ]
Official Symbol KIF11provided by HGNC
Official Full Name kinesin family member 11provided by HGNC
Primary source HGNC:6388
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 EG5; HKSP; KNSL1; TRIP5
Summary This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]
Location : 10q24.1
Sequence : Chromosome: 10; NC_000010.10 (94352825..94415152
Kinesin-like protein KIF11
Kinesin-like protein 1 Kinesin-like spindle protein HKSP Kinesin-related motor protein Eg5 Thyroid receptor-interacting protein 5 Short name=TR-interacting protein 5 Short name=TRIP-5
Gene names: Name: KIF11
Synonyms: EG5, KNSL1, TRIP5
Organismz: Homo sapiens (Human)
Taxonomic identifier: 9606|NCBI
Kinesin superfamily proteins (KIFs) are motor proteins that convert chemical energy, typically in the form of ATP, into mechanical force. They act upon microtubules to move vesicles and organelles within cells and also lead to the beating of flagella and cilia nd act within the mitotic and meiotic spindles to segregate replicated chromosomes to progeny cells.
Generally, kinesins mediate plus-end transport. Kinesins exist as dimers, with a catalytic 'head' domain and a 'stalk/tail' domain that is important in interactions with the cargo molecules. The 'neck' attaches the stalk to the head and is essential in determining direction of motility and regulation of activity. The head and neck (known collectively as the motor domain) are conserved across the family, whilst the stalk is highly divergent, reflecting the wide range of cellular functions of kinesins.
Some specific kinesins have been implicated in human diseases, including Alzheimer's (KIF5), polycystic kidney disease (KIF3A / KIF3B) and diabetes (KIF5B).
KIF-11 (Human) Overview
KIF11 a cytoskeletal protein that belongs to the kinesin-like protein family. BimC subfamily. Interacts with the thyroid hormone receptor in the presence of thyroid hormone. Plays a role in chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. Phosphorylation regulates its association with the spindle apparatus. Note: This description may include information from UniProtKB. Protein type: Motor protein; Microtubule binding protein Cellular Component: spindle pole; kinesin complex; cytoskeleton; chromatin remodeling complex; spindle microtubule; cytoplasm; spindle; cytosol Molecular Function: nucleotide binding; microtubule motor activity; protein kinase binding; ATP binding
Biological Process: mitosis; mitotic spindle organization and biogenesis; mitotic centrosome separation; cell division; cell cycle; blood coagulation; spindle organization and biogenesis; microtubule-based movement
Reference #: P52732 (UniProtKB)
Alt. Names/Synonyms: EG5; HKSP; KIF11; kinesin family member 11; kinesin-like 1; Kinesin-like protein 1; Kinesin-like protein KIF11; Kinesin-like spindle protein HKSP; Kinesin-related motor protein Eg5; KNSL1; thyroid receptor interacting protein 5; Thyroid receptor-interacting protein 5; TR-interacting protein 5; TRIP-5; TRIP5
Gene Symbols: KIF11
Molecular weight: 119,159 Da
Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population.
Furukawa Y, Shimada T, Furuta H, Matsuno S, Kusuyama A, Doi A, Nishi M, Sasaki H, Sanke T, Nanjo K.
The First Department of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
CONTEXT: A genome-wide association study in the French population has detected that novel single-nucleotide polymorphisms (SNPs) in the IDE-KIF11-HHEX gene locus and the SLC30A8 gene locus are associated with susceptibility to type 2 diabetes.
OBJECTIVE: We investigated whether SNPs in these loci were associated with type 2 diabetes in Japanese.
DESIGN: Two SNPs, rs7923837 and rs1111875, in the IDE-KIF11-HHEX gene locus and one SNP, rs13266634, in the SLC30A8 gene locus were genotyped in Japanese type 2 diabetic patients (n = 405) and in nondiabetic control subjects (n = 340) using the TaqMan genotyping assay system.
RESULTS: The G allele of rs7923837 was associated with type 2 diabetes [odds ratio 1.66, 95% confidence interval (CI) 1.28-2.15; P = 0.00014], following the same tendency as in the French population of the previous report. Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.57 (95% CI 1.15-2.16; P = 0.0050) and 3.16 (95% CI 1.40-7.16; P = 0.0038) relative to noncarriers. Although the G allele was a major allele (66.5%) in the French population, it was a minor allele (23.8%) in Japanese. The G allele of rs1111875 was also associated with type 2 diabetes (odds ratio 1.42, 95% CI 1.13-1.78; P = 0.0024). Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.31 (95% CI 0.97-1.77; P = 0.0810) and 2.40 (95% CI 1.34-4.32; P = 0.0028) relative to noncarriers. A significant association with type 2 diabetes was not observed for rs13266634.
CONCLUSIONS: Polymorphisms in the IDE-KIF11-HHEX gene locus are associated with susceptibility to type 2 diabetes across the boundary of race.
Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with CongenitalLymphedema and Chorioretinopathy.
Ostergaard P, Simpson MA, Mendola A, Vasudevan P, Connell FC, van Impel A, Moore AT, Loeys BL, Ghalamkarpour A,Onoufriadis A, Martinez-Corral I, Devery S, Leroy JG, van Laer L, Singer A, Bialer MG, McEntagart M, Quarrell O, Brice G,Trembath RC, Schulte-Merker S, Makinen T, Vikkula M, Mortimer PS, Mansour S, Jeffery S. Source Medical Genetics Unit, Biomedical Sciences, St. George's University of London, London SW17 0RE, UK.
We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated withlymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of KIF11 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. KIF11 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of KIF11 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.
Association between variants in IDE-KIF11-HHEX and plasma amyloid β levels.
Reitz C, Cheng R, Schupf N, Lee JH, Mehta PD, Rogaeva E, St George-Hyslop P, Mayeux R.
The Taub Institute for Research on Alzheimer's Disease and Aging Brain, Columbia University, New York, NY 10032, USA.
Genetic linkage and association studies in late-onset Alzheimer's disease (LOAD) or its endophenotypes have pointed to several regions on chromosome 10q, among these the ∼ 250 kb linkage disequilibrium (LD) block harboring the genes IDE, KIF1, and HHEX. We explored the association between variants in the genomic region harboring the IDE-KIF11-HHEX complex with plasma Aβ40 and Aβ42 levels in a case-control cohort of Caribbean Hispanics. First, we performed single marker linear regression analysis relating the individual single nucleotide polymorphisms (SNPs) with plasma Aβ40 and Aβ42 levels. Then we performed 3-SNP sliding window haplotype analyses, correcting all analyses for multiple testing. Out of 32 SNPs in this region, 3 SNPs in IDE (rs2421943, rs12264682, rs11187060) were associated with plasma Aβ40 or Aβ42 levels in single marker and haplotype analyses after correction for multiple testing. All these SNPs lie within the same LD block, and are in LD with the previously reported haplotypes. Our findings provide support for an association in the IDE region on chromosome 10q with Aβ40 and 42 levels.
CHORIORETINAL DYSPLASIA-MICROCEPHALY-MENTAL RETARDATION SYNDROME
Other entities represented in this entry:
MICROCEPHALY WITH CHORIORETINOPATHY, AUTOSOMAL DOMINANT, INCLUDED
Microcephaly with chorioretinopathy (of a type that suggests congenital infection) in combination with mental retardation was reported by Tenconi et al. (1981). Warburg and Heuer (1983) presented the cases of 2 brothers and their mother who had the combination of microcephaly and lacunar depigmentation of the retina. Microcephaly was slight and the foreheads were bulging. Mental retardation was mild. A 5-year follow-up demonstrated that visual function was stable (Warburg and Heuer, 1994). Manning et al. (1990) reported the electroretinographic findings in members of a possible third family. Male-to-male transmission was observed for the first time in a family reported by Sadler and Robinson (1993); also see Robinson and Sadler (1993). A father and 2 sons were affected. Polycystic kidney disease was segregating in the family, apparently independently of the microcephaly syndrome.
Hordijk et al. (1996) described a father and son with this syndrome. In addition to the usual manifestations, both had microcornea and overgrowth of the conjunctiva over the corneoscleral junction. The father had microphthalmia, and his son was severely mentally retarded. Microphthalmia, microcornea, and severe mental retardation had not been reported in other families with the autosomal dominant form of the syndrome.
Alzial et al. (1980) reported cases of microcephaly and chorioretinopathy with autosomal dominant inheritance. Also see autosomal recessive microcephaly with chorioretinopathy (251270) and the lymphedema, microcephaly, chorioretinopathy syndrome (152950).
Trzupek et al. (2007) reported a sister and brother with mental retardation, severe microcephaly, hypotonia, and variable retinal and choroidal abnormalities. The 12-year-old girl had multiple atrophic and dysplastic-appearing lesions of the retina and choroid bilaterally; an electroretinogram at 5 months of age revealed markedly subnormal scotopic and photopic responses with delayed flicker timing. Her 5-year-old brother had bilateral macular folds with vitreoretinopathy, serous retinal detachments, glaucoma, and cataracts. Trzupek et al. (2007) stated that these are the first sibs in whom these features were observed with unaffected parents.
REFERENCES 1. Alzial, C., Dufier, J. L., Brasnu, C., Aicardi, J., de Grouchy, J. Microcephalie 'vraie' avec dysplasie chorio-retinienne a heredite dominante. Ann. Genet. 23: 91-94, 1980. [PubMed: 6967291, related citations] [Full Text: Pubget]
2. Hordijk, R., van de Logt, F., Houtman, W. A., van Essen, A. J. Chorioretinal dysplasia-microcephaly-mental retardation syndrome: another family with autosomal dominant inheritance. Genet. Counsel. 7: 113-122, 1996. [PubMed: 8831130, related citations] [Full Text: Pubget]
3. Manning, F. J., Bruce, A. M., Berson, E. L. Electroretinograms in microcephaly with chorioretinal degeneration. Am. J. Ophthal. 109: 457-463, 1990. [PubMed: 2330949, related citations] [Full Text: Pubget]
4. Robinson, L. K., Sadler, L. S. Chorioretinal dysplasia-microcephaly-mental retardation syndrome: report of an American family. (Abstract) Proc. Greenwood Genet. Center 12: 54 only, 1993.
5. Sadler, L. S., Robinson, L. K. Chorioretinal dysplasia-microcephaly-mental retardation syndrome: report of an American family. Am. J. Med. Genet. 47: 65-68, 1993. [PubMed: 8368255, related citations] [Full Text: Pubget]
6. Tenconi, R., Clementi, M., Battista Moschini, G., Casara, G., Baccichetti, C. Chorio-retinal dysplasia, microcephaly and mental retardation: an autosomal dominant syndrome. Clin. Genet. 20: 347-351, 1981. [PubMed: 7333029, related citations] [Full Text: Pubget]
7. Trzupek, K. M., Falk, R. E., Demer, J. L., Weleber, R. G. Microcephaly with chorioretinopathy in a brother-sister pair: evidence for germ line mosaicism and further delineation of the ocular phenotype. Am. J. Med. Genet. 143A: 1218-1222, 2007. [PubMed: 17486591, related citations] [Full Text: John Wiley & Sons, Inc., Pubget]
8. Warburg, M., Heuer, H. E. Autosomal dominant microcephaly with lacunar retinal hypopigmentations.In: Henkind, P. : XXIV International Congress Ophthalmology. Philadelphia: J. B. Lippincott (pub.) 1983.
9. Warburg, M., Heuer, H. E. Chorioretinal dysplasia-microcephaly-mental retardation syndrome. (Letter) Am. J. Med. Genet. 52: 117 only, 1994. [PubMed: 7977454, related citations] [Full Text: Pubget]\
Microcephaly Chorioretinopathy Syndrome Lymphedema People