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Linking Human Disease Genes With C. Elegans Genes

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Human Disease Genes and C. elegans Genes

Although the phenotypes of the human diseases and the mutant defects in C. elegans seem about as unrelated as possible, the cellular and molecular details of many of these defects are highly related. Using C. elegans as a model organism, much can be learned at the cellular and molecular level about a specific biological process, by understanding the mode of action of the orthologous genes involved.

The recent findings suggest the absence of the mammalian organ(s) affected by a disease does not preclude the use of nematodes to shed light on complex disease mechanisms and find novel target genes for treatments. For example, the ksr gene, discovered in C. elegans has recently been proposed as a druggable target to overcome Ras-driven cancers .

Disease Gene Finder

The table below illustrates the link between human disease genes and C. elegans genes and their corresponding phenotypes.

This table does not constitute a thorough list of genes and phenotypes for the diseases mentioned.

If you don’t see your gene of interest listed, feel free to contact us.

Human disease Organ Human Gene Human phenotype C. elegans gene C. elegans phenotypes
Aarskog–Scott syndrome various FGD1 distinctive facial features, mild to moderate short stature during childhood, sometimes heart defects exc-5 endosome localization defects, excretory canal morphology defects, locomotion defects, organism morphology defects, sterility
Achondroplasia bones FGFR3 developmental delay, poorly defined organelles, short-limbed dwarfism, megalocephaly, spinal and facial deformity egl-15 distinctive facial features, mild to moderate short stature during childhood, sometimes heart defects
Acute myeloid leukaemia myeloid line of blood cell c-CBL (proto-oncogene) sli-1 vulval lineage defects, larval lethality (when combined with let-23 mutation), low penetrance non-lethal head deformity.
Adrenoleukodystrophy, X-linked nervous system and the adrenal glands ALD pmp-4 --
Alagille Syndrome liver, heart, and other organs and body parts JAG1 impaired differentiation of intrahepatic bile ducts, defects in heart, eye and kidney development. arg-1 germ cell differentiation defect, accumulated germline cell corpses
Alcoholic liver disease and alcoholic cirrhosis a liver NCALD asymtomatic SMN patients with SMN-1 deletions have reduce expression of NCALD ncs-1 ameliorates pharyngeal pumping defects of smn-1 mutants
Alzheimer disease, type 4 brain PS2 memory loss, Neurofibrillary tangles, tau tangles, a-beta protein accumulation sel-12 chemical hypersensitive, weakened neuromuscluar function, developmental defects
Amyotrophic lateral sclerosis brain, spinal cord VAPB/ALS8/hVAP muscle weakness, altered phosphorylation of neurofilaments, shortened life span vpr-1 actin organization defect, mis-positioning of specific head neurons, early lethality, sterile
Amyotrophic lateral sclerosis brain, spinal cord SOD1 muscle weakness, altered phosphorylation of neurofilaments, shortened life span sod-1 myosin organization defect, egg laying defects, germ cell development defects, shortened life span, increased protein phosphorylation
Aniridia eye PAX6 eye morphology defects, likely due to abnormal neuronal migration and misspecification of neurons. vab-3 morphology defects, axon guidance defects, cell fate specification defects, dopaminergic fate atypical
Ataxia telangiectasia immune system ATM weak immune system, likely due to disturbed lymphocyte cell fate acquisition, delayed motor development, higher risk of cancer let-363 delayed development, cell fate specification defects, adult growth defects, reduced cell proliferation, abnormal life span, tumor prolapse frequency decreased
Autoimmune polyglandular syndrome endocrine gland AIRE T cell activation, proliferation and differentiation defect, muscle pain and cramping, weakness and fatigue let-418 pharyngeal morphology defects, cell differentiation defects, cell fate transformation
Barth syndrome heart BTHS dilated cardiomyopathy, muscle weakness, recurrent infections due to small numbers of white blood cells, short stature. acl-3 --
Benign familial neonatal convulsions brain KCNQ2 newborns show tonic-clonic seizures, sometimes changes of heart rate, respiration and systemic blood pressure kqt-1 pharyngeal pumping arrhythmia
Bloom syndrome various BLM defective chromosomal disjunction at the end of meiosis, male sterility, predisposition to cancer and genomic instability him-6 defective chromosomal disjunction, germline defects, male sterility, high incidence male progeny
Bor syndrome ear EYA1 hearing loss and other ear abnormalities, likely due to abnormal apoptosis of organ primordia eya-1 apoptosis increased, body size defects, apoptosis increased, cell migration and apoptosis
Boston Type Craniosynostosis cranium, face MSX2 premature closure of coronal suture CEH-24 paralysis, reduced brood size, increased lethality, general sickness
Cancer b various RAS/RAF/MEK/ERK cell proliferation defect during development let-60/lin-45/mek-, mpk-1 vulva development impairment
Cancer various ESPL1 tumorigenesis sep-1 multinucleate cells, embryos fail to develop
Cancer various FOS metastasis fos-1a anchor cell invasion into the vulval epithelium
Cancer c various RAS family (proto-oncogenes) improper signal transduction, proliferation and malignant transformation ksr aberrant cell specification (multivulva)
Cancers d various p53, BRCA1 cancer (various) him gene family high incidence of males
Cerebral cavernous malformation brain, spinal cord CCM3/PDCD10 cerebral cavernous malformations ccm-3 excretory cell defect
Ceroid lipofuscinosis, infantile neuronal nervous system INCL developmental regression, decreased muscle tone, intellectual and motor disability, muscle twitches, epilepsy, brain atrophy, microcephaly, and vision loss ppt-1 body morphology defect, locomotion, life span, increased thrashing
Chondrodysplasia punctata bones ARSE skeletal abnormalities, distinctive facial features, intellectual disability, and respiratory problems sul-2 --
Choroideraemia eye CHM progressive vision loss, ultimately leading to complete blindness haf-8 --
Citrullinaemia, adult onset type II blood SLC25A13 accumulation of ammonia and other toxic substances in the blood K02F3.2 sterile
Congenital adrenal hyperplasia adrenal glands CYP21 constipation, decreased growth, enlarged genitalia cyp-33C4 short defecation cycle, slow growth
Congenital nephrotic syndrome 1 kidneys NPHS1 abnormal muscle contractions due to loss of inhibition of motor neurons, high fat level in the blood and urine syg-2 locomotion, fat accumulation, presynaptic vesicle cluster defects
Coronal craniosynostosis cranium, face E proteins (TCF12) premature closure of coronal suture hlh-2 cell fate specification and migration defect
Cyclic haematopoiesis blood cells ELA2 blood-cell production from the bone marrow oscillates with 21-day periodicity. try-2 dauer lifespan extended, sterile
Cystic fibrosis lungs, pancreas, liver, kidneys, and intestine CFTR diagnostic before 1 year old, lethal within months without treatment; poor growth, poor weight gain, accumulation of mucus mrp-4 embryonic lethal
Darier disease skin ATPLA2 dark crusty patches on the skin, sometimes containing pus. sca-1 body wall muscle myosin organization defective, endoplasmic reticulum metabolism defects, shortened life span, morphology defect
Deafness, conductive ear POU3F4 deafness ceh-6 gonad development, clear appearance, developmental defect, rectal development defects
Deafness, autosomal recessive 9 ear OTOF deafness fer-1 fertility defect, sperm defect
Deafness, neurosensory, autosomal recessive 3 ear MYO15 profound deafness hum-6 --
Deficiency of coagulation factors V/VIII blood ERGIC-53 impaired blood coagulation ile-1 --
Dent disease kidneys CLCN5 damaged proximal tubules, abnormally large amount of proteins in the urine, kidney stones. clh-5 muscle arm development defects, sterile
Diastrophic dysplasia various DTD abnormal morphology with short stature, joint pain and deformities restricting movement sulp-5 --
Dyskeratosis congenita, X-linked various DKC1 nail dystrophy, changes pigmentation). K01G5.5 developmental delay postembryonic, sterility
Epidermolytic palmoplantar keratoderma skin KRT9 thickening of the palms and soles associated with more generalized skin disorders mua-6 epidermis cuticle detached, abnormally clear body, foraging behavior, growth defect, body muscle displaced, egg laying defects, developmental defect
FGFR-related craniosynostosis spectrum cranium, face FGF receptors1,2 and 3 premature closure of coronal suture egl-15 axon guidance defects, locomotion and egg laying defects
Fragile histidine triad esophageal, stomach, and colon FHIT increased resistance to DNA-damaging stressors like UVC lights; esophageal, stomach, and colon carcinomas nft-1 organism UV resistant, germline defects
Fragile site mental retardation, type 2 brain and other organs FMR2 long and narrow face, large ears, flexible fingers, and large testicles, hyperactivity seizures F35A5.1 --
Friedreich ataxia brain FRDA swallowing dysfunction, ATP content deficiency in lymphocytes, impaired muscle coordination and locomotion, nervous system damage frh-1 feeding behavior defects, ATP levels reduced, locomotion defect, development defect, extended life span
Glycerol kinase deficiency various GK accumulation of glycerol in the blood and urine, vomiting and lethargy. R11F4.1 --
Gonadal dysgenesis reproductive system SRY absence of testis differentiation, progressive loss of germ cells on the embryo gonads, increased muscle mass in adult sox-2 cell fate transformation, gonad defect, reduced brood size, locomotion defect, general sickness
Groenouw granular dystrophy, type 1 eyes (cornea) BIGH3 multiple small deposits in the superficial central corneal stroma, and progressive visual impairment, F26E4.7 developmental defect, germline defects
Hereditary megaloblastic anaemia blood cells CUBN fatigue, paleness of the skin, shortness of breath, light headedness, dizziness, fast or irregular heartbeat. ZC116.3 slow growth, embryonic lethal, sterility
Hereditary multiple exostoses bones EXT1 develop multiple benign (noncancerous) bone tumors rib-1 protruding vulva, pharyngeal development defects
Hereditary non-polyposis colon cancer colon MLH1 mlh-1 spontaneous mutation rate increased, sterile, embryo lethality
Hermansky–Pudlak syndrome eyes HPS abnormally light coloring (pigmentation) of the skin, hair, and eyes apm-3 --
Holt–Oram syndrome heart, skeleton TBX5 poor growth, skeletal abnormalities of upper limbs, easy fatigability with exercise, arrhythmias tbx-2 slow growth, motor defects, pharyngeal (pumping organ) development defects, neuron development and migration defects
Hyperekplexia brain GLRA2 pronounced startle responses to tactile or acoustic stimuli and hypertonia avr-14 starvation enhance gustatory plasticity, locomotor coordination, chemotaxis
Hypophosphataemic rickets, X-linked bones XLH bone deformity including short stature and genu varum (bow leggedness). nep-11 --
Kallmann syndrome various KAL delayed or absent puberty and an impaired sense of smell. K04F10.1 --
Long QT syndrome, type 1 heart KVLQT1 cardiac arrhythmia, seizures, increased frequency observed in inflammatory bowel disease kqt-3 defecation cycle variable length, Bacillus thuringiensis toxin hypersensitive, long defecation cycle, pharyngeal pumpoiugn arrhythmia, pore forming toxin hypersensitive
Lowe syndrome eye OCRL Germline mosaicism, involuntary, rapid eye movements, hypotonia, postnatal kidney defects and intellectual disability ocrl-1 accumulated germline cell corpses, locomotion defect, early eggs laid, slow development,
Marfan syndrome heart, blood vessels, bones, joints, and eyes FBN1 aortic enlargement, Long arms, legs and fingers,Chest sinks in or sticks out, Flexible joints fbn-1 developmental defect, fertility defects, Fluorouracil resistant, locomotion defects, slow growth
Myotonic dystrophy muscles DM gradual muscle loss and weakness, muscles contraction defect, facial dysmorphia mrck-1 locomotion defects, organism morphology defects, slow growth
Myotubular myopathy skeletal muscles MTM1 muscle weakness, decreased muscle tone evident at birth. itsn-1 protein subcellular localization defects
Nevoid basal cell carcinoma syndrome various PTC defects within multiple body systems (skin, nervous system, eyes, endocrine system, and bones) ptc-1 avoids food, developmental defect, reduced fat content, morphology defect, fertility defects
Nigmegen breakage syndrome various nibrin short stature, an unusually small head size (microcephaly), distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, intellectual disability, and other health problems, immunodeficiency xnp-1 accumulated germline cell corpses, everted vulva, gonad development defect
Non-syndromic deafness DFNA1 ear DIAPH1 hearing loss lgc-38 --
Opitz syndrome Genetic disease MID1 ranging from mild intellectual disability and behavioural problems to lethal malformations arc-1 --
Pancreatic carcinoma pancreas DPC4 jaundice, bloating, loss of appetite sma-4 locomotion defects, organism morphology defects, multivulva
Parkinson disease juvenile 2 brain PARKIN PINK-1 protein aggregation, rigidity, resting tremor reduction of mitochondrial complex I activity, disruption of the mitochondrial morphology, and impairment of protection of mitochondrial genomic integrity from oxidative stress. pdr-1 pink-1 protein aggregation, rigidity, resting tremor reduced mitochondrial activity, disrupted mitochondrial morphology, reduced protection from oxidative stress, linked to manganese exposure
Parkinson's disease brain LRRK2 protein aggregation, muscular weakness, dopaminergic sigalling loss lrk-1 pesticide response
Polycystic kidney disease, type 1 kidney PKD1 erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes lov-1 male mating defects, locomotion and posture defect, increased girth, slow growth
Premature Aging various WRN defective pigmentation, skin atrophy, loss of cutaneous fat, ulceration wrn-1 abnormally clear appearance, aging, cell cycle timing, growth rate, shortened larva
Retinitis pigmentosa 3, X-linked eye (retina) RP3 night blindness, field constriction, and pigmentary changes in the retina glo-4 axon termination defective, fat content reduced, organelle morphology defects,
Retinoblastoma eye RB1 apoptosis defects, tumor formation, abnormal appearance of the retina lin-35 reduced apoptosis, increased cell proliferation, egg laying defects, pharyngeal morphology defects, fertility and developmental defect,
Retinoschisis X-linked juvenile eyes (retina) XLRS1 retinal morphological changes, impaired vision ddr-1 lysosome-related organelle morphology defects, RAB-11 recycling endosome morphology defects
Rieger syndrome various RIEG maldevelopment of the neural crest cells, absent or under-developed teeth, craniofacial abnormalities, and abnormalities of the eye unc-30 axon outgrowth defects, neuron morphology defects, locomotion defect
saethre-Chotzen Syndrome cranium, face TWIST family Neural crest cell migration and function defect hlh-8 muscle defects (egg laying defect, constipation)
Schizophrenia brain DISC1 defects in neuronal connectivity during development, disorganized speech or behavior, and decreased participation in daily activities, difficulty with concentration and memory. none --> KI with mDISC1 axon guidance defects
Simpson–Golabi–Behmel syndrome various GPC3 infants larger than normal at birth unusual growth and weight gain gpn-1 --
Spinal muscular atrophy brain, spinal cord SMN progressive motor neuron degeneration, muscle weakness smn-1 slow growth, larval lethality, and impaired neuromuscular function in pharyngeal pumping during feeding
Spinocerebellar ataxia 2 nervous system SCA2 uncoordinated movement, speech and swallowing difficulties, muscle wasting, slow eye movement, and sometimes dementia. atx-2 developmental defects, germline defect
Stargardt disease eye (macula) ABCR progressive damage—or degeneration—of the macula abt-4 --
T-cell acute lymphoblastic leukemia blood cells Notch signalling increase in white blood cells Notch signalling cell fate transformations
Thiamine-responsive megaloblastic anaemia various SLC19A2 hearing loss, diabetes, and blood calledmegaloblastic anemia folt-2 --
Tuberous sclerosis Genetic disease TSC2 seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, and lung and kidney disease. sipa-1 --
Velocardiofacial/DiGeorge Syndrome cranium, face, brain and other organs TBX1 congenital heart problems, specific facial features, frequent infections, developmental delay, learning problems, and cleft palate mls-1 uterine muscle cell fate specification defect
Waardenburg syndrome various PAX3 deafness, white forelock (a frontal white blaze of hair), a difference of color between the iris of one eye and the other (heterochromia iridis), white eye lashes, and wide-set inner corners of the eyes. alr-1 touch resistant
Wilms tumour kidneys WT1 klf-2 locomotion defects
Wilson disease liver, brain and other vital organs WND swelling, fatigue, abdominal pain, and uncontrolled or poorly coordinated movements cua-1 aging defect, axon fasciculation defects, body wall muscle morphology defects, locomotion defects, paralyzed, shortened life span, slow growth
Wiskott–Aldrich syndrome WASP eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). wsp-1 cell migration failure, axon guidance defect
α1-antitrypsin deficiency (ATD) liver ATM/ATZ fibrosis/cirrhosis and carcinogenesis none --> KI with human ATM/ATZ aggregation in Endoplasmic reticulum of intestinal cells, enhanced autophagy in ATZ animals


  1. This is a fine example of how modifier mutations can be validated using different model organisms in which a given disease gene is being modeled.
  2. The genetic pathways were practically identical: the tyrosine kinase growth factor receptor-Ras-Raf-MEK-MAPK pathway. the same set of orthologs is required for these three biological processes: vulval induction in C. elegans, eye development in D. melanogaster, and cell proliferation in mammalian cell culture.
  3. Identification of the ksr gene in D. melanogaster and C. elegans in the mid-1990s. The discovery of this gene has great medical implications for cancer.
  4. Cancer and the Him phenotype are both the result of chromosome segregation defects.
  5. Neil S. Dhawan, Alex P. Scopton & Arvin C. Dar. Nature 537, 112–116 (01 September 2016).doi:10.1038/nature19327

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