Home > Resources > Linking Human Disease Genes with 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 .
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 |
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