INT254428

Context Info Confidence 0.44 First Reported 2008 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 4 Total Number 5 Disease Relevance 1.52 Pain Relevance 0.11

anatomical structure development (Lrp4) plasma membrane (Lrp4)

Anatomy Link Frequency Tid1 1 femur 1 Lrp4 (Mus musculus)

Pain Link Frequency Relevance Heat Serotonin 14 80.12 Pain 2 65.84 antagonist 7 50.00 anesthesia 2 35.28 agonist 2 16.00 cINOD 4 5.00 imagery 4 5.00 midbrain 2 5.00 adenocard 2 5.00 Inflammatory response 2 5.00

Disease Link Frequency Relevance Heat Congenital Myasthenic Syndromes 44 98.96 Congenital Anomalies 12 97.36 Osteoporosis 64 92.80 Disease 27 91.16 Bone Cancer 13 90.96 Syndrome 16 68.04 Pain 2 65.84 Retina Disease 2 65.44 Cancer 8 56.96 Fracture Healing 10 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

These mutations were either in the gene encoding the low density lipoprotein receptor-related protein-5 (LRP5) or in a gene (SOST) encoding a protein (Sclerostin) that potentially binds and regulates the function of LRP5 and its family members LRP4 and LRP6.

LRP4 Binding (binds) of

1) Confidence 0.44 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.18 Pain Relevance 0.04

In addition, it has recently been shown that LRP4, which is expressed in bone and cultured osteoblasts, binds Dkk1 and sclerostin in vitro and that Lrp4-deficient mice revealed shortened total femur length, reduced cortical femoral perimeter, reduced total femur bone mineral content (BMC), and bone mineral density (BMD) [58].

LRP4 Binding (binds) of in femur

2) Confidence 0.33 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.64 Pain Relevance 0.07

When tested in the overall BMD cohort, these regions did achieve moderate level association with BMD (2p16, P = 8 × 10-7; LRP4, P = 3 × 10-4).

LRP4 Binding (association) of

3) Confidence 0.24 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592817 Disease Relevance 0.14 Pain Relevance 0

We found that the interaction of the patient's MuSK mutants with the co-receptor of agrin Lrp4 was not affected.

Lrp4 Binding (interaction) of

4) Confidence 0.16 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2876883 Disease Relevance 0.28 Pain Relevance 0

Our findings demonstrate that missense mutations in MUSK can result in a severe form of CMS and indicate that the inability of MuSK mutants to interact with Dok-7, but not with Lrp4 or Tid1, is a major determinant of the pathogenesis of the CMS caused by MUSK mutations.

Lrp4 Binding (interact) of in Tid1 associated with congenital myasthenic syndromes

5) Confidence 0.15 Published 2010 Journal Human Molecular Genetics Section Abstract Doc Link PMC2876883 Disease Relevance 0.27 Pain Relevance 0

General Comments

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