Human Disease Model Report: obesity, susceptibility to (postulated), PLXND1-related

General Information

Name

obesity, susceptibility to (postulated), PLXND1-related

FlyBase ID

FBhh0001025

Disease Ontology Term

obesity

Parent Disease

obesity, susceptibility to (fly models overview)

OMIM

Overview

The human gene PLXND1 was identified in a meta-analysis of protein-coding genetic variants that influence waist-to-hip ratio, after adjusting for body mass index, which is associated with increased risk of type 2 diabetes and coronary heart disease. The analysis included 476,546 individuals, 88% with European ancestry and 12% with South and East Asian, African, or Hispanic/Latino ancestry. PLXND1 has not been introduced into flies.

There are two orthologous genes in flies, PlexA and PlexB, with PlexB receiving the higher orthology score by DIOPT. Multiple RNAi targeting constructs and P-element insertion lines have been generated for PlexB.

PlexB knockdown using a neuronal GAL4 driver causes a significant increase in the levels of triglycerides, but no effect was seen using a fat body driver.

[updated May 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: obesity, susceptibility to (fly models overview)

Symptoms and phenotype

Obesity is an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. Obesity is associated with increased risk of illness, disability, and death. (http://medical-dictionary.thefreedictionary.com/obesity).

(FlyBase Curators, 2013-)

The development of obesity is recognized as having both genetic and environmental components (https://www.sciencelearn.org.nz/resources/203-obesity-genetic-or-environmental).

(FlyBase Curators, 2013-)

Specific Disease Summary: obesity, susceptibility to (postulated), PLXND1-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

PLXND1 encodes a semaphorin receptor gene involved in cell signaling and growth regulation for tissues in the cardiovascular, skeletal, and central nervous systems, as well as angiogenesis. It has been implicated in type 2 diabetes and is highly expressed in adiopose tissue (Justice et al. 2019, FBrf0241652). In Drosophila, PlexB is a receptor for the secreted semaphorin Sema2a. It participates in central and peripheral axon pathfinding during development (Ayoob et al. 2006, FBrf0190270).

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): PLXND1
Gene Cards: PLXND1
MedlinePlus (gene): PLXND1
MARRVEL (human gene): PLXND1
NCBI (Entrez) gene: PLXND1; plexin D1

Disease synonyms

Related Diseases

Related human health report(s)

obesity, susceptibility to (fly models overview)

Related Specific Diseases

OMIM phenotypic series

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

PLXND1; plexin D1

D. melanogaster ortholog (based on DIOPT)

Dmel\PlexB

(DIOPT, 2013-)

Dmel\PlexA

(DIOPT, 2013-)

Comments on ortholog(s)

Many human genes to two Drosophila genes; PlexB has the best score. Human genes paralogous to PLXND1 that PlexB is orthologous to include: PLXNB1, PLXNB2, PLXNB3, PLXNA1, PLXNA2, PLXNA3, PLXNA4, and PLXNC1.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (2)

Dmel\PlexB

Gene Snapshot

Plexin B (PlexB) encodes a transmembrane receptor for ligands including semaphorins, which signals via RhoGTPases. It can signal both attractive and repulsive axon guidance. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

PLXN

Comments on ortholog(s)

High-scoring ortholog of PLXND1, has best score.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\PlexA

Gene Snapshot

Plexin A (PlexA) encodes a transmembrane receptor for Semaphorin ligands encoded by Sema1a and Sema1b. The intracellular region of this receptor has GTPase activating protein (GAP) activity on Ras/Rap small GTPases. The signaling by the product of PlexA alters actin, microtubules and cell adhesion in developmental processes such as axon guidance. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of PLXND1, has lower score than PlexB.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (19 groups)

PlexB

protein-protein

Interacting group

Assay

References

PlexB - fra

anti tag coimmunoprecipitation, anti tag western blot, western blot

(Zang and Bashaw, 2023)

PlexB - mys

proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot

(Orr et al., 2022, Meltzer et al., 2016)

PlexB - PlexA

two hybrid, anti tag coimmunoprecipitation, western blot, anti tag western blot

(Chak and Kolodkin, 2014, Ayoob et al., 2006)

PlexB - Rac1

pull down, autoradiography

(Driessens et al., 2001, Hu et al., 2001)

PlexB - Rac2

pull down, autoradiography

(Hu et al., 2001)

PlexB - Rho1

pull down, autoradiography

(Hu et al., 2001)

PlexB - RhoGAPp190

anti tag coimmunoprecipitation, anti tag western blot

(Jeong et al., 2012)

PlexB - Sema2a

genetic interference, affinity technology, light microscopy, tag visualisation, inferred by author, microscale thermophoresis, predetermined participant

(Rozbesky et al., 2019, Wu et al., 2011, Ayoob et al., 2006)

PlexB - Sema2b

microscale thermophoresis, predetermined participant, genetic interference, affinity technology, light microscopy, tag visualisation

(Rozbesky et al., 2019, Wu et al., 2011)

PlexA

protein-protein

Interacting group

Assay

References

PlexA - 14-3-3ε

anti tag coimmunoprecipitation, western blot, anti tag western blot, pull down, two hybrid

(Yang and Terman, 2012)

PlexA - Gyc76C

anti tag coimmunoprecipitation, anti tag western blot

(Chak and Kolodkin, 2014)

PlexA - Mical

two hybrid, anti bait coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, western blot

(Yoon et al., 2017, Yang and Terman, 2012, Terman et al., 2002)

PlexA - otk

anti tag coimmunoprecipitation, anti tag western blot

(Winberg et al., 2001)

PlexA - pbl

anti tag coimmunoprecipitation, anti tag western blot

(Jeong et al., 2012)

PlexA - PlexB

two hybrid, anti tag coimmunoprecipitation, western blot, anti tag western blot

(Chak and Kolodkin, 2014, Ayoob et al., 2006)

PlexA - Ras64B

anti tag coimmunoprecipitation, anti tag western blot

(Yang and Terman, 2012)

PlexA - RhoGAPp190

anti tag coimmunoprecipitation, anti tag western blot

(Jeong et al., 2012)

PlexA - Sema1a

surface plasmon resonance, predetermined participant, bead aggregation assay, fluorescence microscopy, inferred by author, enzyme linked immunosorbent assay, microscale thermophoresis, phenotype-based detection assay

(Rozbesky et al., 2020, Rozbesky et al., 2020, Rozbesky et al., 2019, Stedden et al., 2019, Hsieh et al., 2014, Winberg et al., 1998)

PlexA - Sema1b

x-ray crystallography, fluorescent resonance energy transfer, fluorescence microscopy, enzyme linked immunosorbent assay, microscale thermophoresis, predetermined participant, molecular sieving, light scattering

(Rozbesky et al., 2020, Rozbesky et al., 2019, Stedden et al., 2019, Winberg et al., 1998)

PlexA - Sema5c

enzyme linked immunosorbent assay

(Stedden et al., 2019)

Alleles Reported to Model Human Disease (Disease Ontology) (8 alleles)

PlexB

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

PlexB^GD14473