Table 1.
List of bHLH-PAS genes and their functions from animals commonly studied for biomedical research
| Species | bHLH–PAS gene name |
bHLH–PAS protein name | Protein class | Function of protein | Reference (PMID) |
|---|---|---|---|---|---|
| Caenorhabditis elegans | aha-1 | AHA-1 | II | Mutation is larval lethal Neuronal specification with ahr-1 Hypoxic transcriptional response with hif-1 Ortholog of human ARNT/ARNT2 |
14757639 19632181 |
| Mus musculus | Ahr | AHR | I | Angiogenesis and hematopoiesis Xenobiotic metabolism Development and function of the immune system Immune checkpoint regulation Regulation of viral replication Liver development and function |
15590894 16443691 33941684 7732381 8806883 34446714 33408169 33239445 32690969 27783946 27158906 26005855 21068375 20676095 20676092 |
| Homo sapiens | AHR | AHR | I | Angiogenesis and hematopoiesis Xenobiotic metabolism Immune response Mutation associated with retinitis pigmentosa |
21976023 21999944 23723449 29726989 |
| Caenorhabditis elegans | ahr-1 | AHR-1 | I | Neuron development Aggregation on lawns of bacterial food Lifespan |
33349622 24655420 16919260 15136141 14757639 |
| Danio rerio | ahr1a | Ahr1a | I | Unclear ( possible role in transcription in endothelial cells) | 30907958 28817646 |
| Danio rerio | ahr1b | Ahr1b | I | Unclear ( possible role in transcription in endothelial cells) | 30907958 28817646 |
| Danio rerio | ahr2 | Ahr2 | I | Xenobiotic metabolism Immune response Fin development Vascular morphology Craniofacial development |
30907958 22242167 28817646 32384158 29494622 |
| Mus musculus | Ahrr | AHRR | indeterminate | Regulate AHR activity Modulate xenobiotic metabolism |
17949687 9887096 |
| Homo sapiens | AHRR | AHRR | indeterminate | Represses AHR transcription activity Possible tumor supressor in cancers |
17890447 18172554 |
| Danio rerio | ahrra | Ahrra | indeterminate | Modulate Ahr2 activation by dioxins Possible role in hematopoiesis |
19494032 24675095 18000031 |
| Danio rerio | ahrrb | Ahrrb | indeterminate | Modulate Ahr2 activation by dioxins | 19494032 18000031 |
| Mus musculus | Arnt | ARNT (HIF1β) | II | Binding partner of multiple Class I bHLH–PAS transcription factors | 27782878 26245371 28602820 7592839 17023418 |
| Homo sapiens | ARNT | ARNT (HIF1β) | II | Binding partner of multiple Class I bHLH–PAS transcription factors | 8662957 27782878 |
| Danio rerio | arnt | Arnt (Hif1β) | II | Binding partner of multiple Class I bHLH–PAS transcription factors | 16306231 16936225 Edwards et al. bioRxiv 2022 |
| Mus musculus | Arnt2 | ARNT2 | II | Binding partner of multiple Class I bHLH–PAS transcription factors | 8657146 10873592 31585079 |
| Homo sapiens | ARNT2 | ARNT2 | II | Binding partner of multiple Class I bHLH–PAS transcription factors Mutation causes post-natal microcephaly, visual and renal anomalies |
24022475 27782878 |
| Danio rerio | arnt2 | Arnt2 | II | Binding partner of multiple Class I bHLH–PAS transcription factors | 19374551 19234064 16936225 Edwards et al. bioRxiv 2022 |
| Mus musculus | Arntl | ARNTL (BMAL1) | II | Binding partner of CLOCK and NPAS2 Circadian rhythm regulation |
17417633 9160755 9616112 |
| Homo sapiens | ARNTL | ARNTL (BMAL1) | II | Binding partner of CLOCK and NPAS2 Circadian rhythm regulation |
17417633 9616112 27782878 |
| Danio rerio | arntl1a | Arntl1a | II | Circadian rhythm regulation with clock genes Ortholog of human ARNTL |
23468616 |
| Danio rerio | arntl1b | Arntl1b | II | Circadian rhythm regulation with clock genes Ortholog of human ARNTL |
23468616 |
| Mus musculus | ARNTL2 | ARNTL2 (BMAL2) | II | Binding partner of CLOCK and NPAS2 Circadian rhythm regulation |
11207387 20153195 |
| Homo sapiens | ARNTL2 | ARNTL2 (BMAL2) | II | Binding partner of CLOCK and NPAS2 Circadian rhythm regulation | 10964693 |
| Danio rerio | arntl2 | Arntl2 (Bmal2) | II | Circadian rhythm regulation | 11517315 |
| Caenorhabditis elegans | cky-1 | CKY-1 | I | Speculated to be functionally similar to NPAS4 | 14701734 19284974 |
| Drosophila melanogaster | clk | Clock | I | Circadian regulation with cyc Regulation of circadian genes per and tim |
11106063 |
| Mus musculus | Clock | CLOCK | I | Circadian rhythm regulation Circadian regulation of genes in multiple tissues |
17417633 9160755 9616112 |
| Homo sapiens | CLOCK | CLOCK | I | Circadian rhythm regulation Circadian regulation of genes in multiple tissues |
17417633 9616112 |
| Danio rerio | clocka | Clocka | I | Circadian rhythm regulation Mesoderm patterning |
18800057 28687631 23468616 18569451 |
| Danio rerio | clockb | Clockb | I | Speculated function circadian rhythm regulation | 23468616 |
| Drosophila melanogaster | cyc | Cycle | II | Circadian regulation with clk Sensitization to cocaine |
11106063 10409723 10446052 |
| Drosophila melanogaster | dysf | Dysfusion | I | Required for tracheal migration, adhesion and fusion during development Joint formation in legs |
16914738 12897136 17652079 25329825 30080872 |
| Drosophila melanogaster | gce | Germ-cell expressed bHLH–PAS | indeterminate | Responds to juvenile hormone Can form heterodimer with met |
26161662 16516852 |
| Caenorhabditis elegans | hif-1 | HIF-1 | I | Stimulates gene expression in response to hypoxia Essential for heat acclimation |
11427734 30696318 12686697 |
| Mus musculus | Hif1a | HIF1A | I | Up-regulates genes in response to hypoxia Hematopoiesis |
24141110 9436976 |
| Homo sapiens | HIF1A | HIF1A | I | Regulates genes in response to hypoxia Vascular devleopment |
9436976 9782081 |
| Danio rerio | hif1aa | Hif1aa | I | Up-regulates genes in response to hypoxia Hematopoesis Neural protective |
29339404 31314708 |
| Danio rerio | hif1ab | Hif1ab | I | Up-regulates genes in response to hypoxia Hematopoesis Maturation of intestinal goblet cells |
29339404 31314708 |
| Danio rerio | hif1al | Hif1al | I | Up-regulates genes in response to hypoxia Regulates erythropoiesis Ortholog of human HIF3A |
33037038 23034716 26052946 |
| Danio rerio | hif1al2 | Hif1al2 | I | Maturation of intestinal goblet cells Speculated up-regulates genes in response to hypoxia |
27222589 |
| Mus musculus | Epas1 | HIF2A | I | Regulates gene expression in response to hypoxia Hematopoesis Regulates vascular endothelial growth factor (VEGF) Spermatogenesis |
15626745 20181618 15851592 |
| Homo sapiens | EPAS1 | HIF2A | I | Regulates gene expression in response to hypoxia Vascular development Mutation causes familial erythrocytosis |
15851592 18184961 |
| Danio rerio | epas1a | Epas1a | I | Up-regulates genes in response to hypoxia hematopoesis ortholog of human EPAS1 (HIF2A) |
29339404 |
| Danio rerio | epas1b | Epas1b | I | Up-regulates genes in response to hypoxia Hematopoesis ortholog of human EPAS1 (HIF2A) |
29339404 |
| Mus musculus | Hif3a | HIF3A | I | Inhibits/represses expression of hypoxia-induced genes | 25626335 9840812 11734856 |
| Homo sapiens | HIF3A | HIF3A | I | Modulates expression of hypoxia-induced genes Dominant negative regulator of HIF1A |
11573933 16126907 19694616 9840812 |
| Caenorhabditis elegans | hlh-34 | HLH-34 | I | Unknown, expressed in a subset of interneurons Ortholog of human NPAS3 |
34604715 |
| Drosophila melanogaster | met | Methoprene-tolerant | indeterminate | Responds to juvenile hormone Mutants are resistant to insecticide methoprene Can form heterodimer with Germ-cell expressed |
1592245 26161662 9501163 15720391 16516852 |
| Mus musculus | Ncoa1 | NCOA1 | indeterminate | Transciptional coactivator of steroid hormone receptors Energy metabolism and obesity Possible regulator of hematopoiesis |
8616895 7481822 12954634 12507421 27958775 |
| Homo sapiens | NCOA1 | NCOA1 | indeterminate | Transcriptional coactivator of steroid hormone receptors Transcriptional coactivator of STAT5 transcription factor |
9427757 7481822 9223431 12954634 9252329 |
| Danio rerio | ncoa1 | Ncoa1 | indeterminate | Transcriptional coactivator of steroid hormone receptors Hematopoiesis |
27958775 30448381 27156127 |
| Mus musculus | Ncoa2 | NCOA2 | indeterminate | Transcriptional coactivator of steroid hormone receptors Energy metabolism and obesity Fertility |
9238002 8670870 12507241 12138202 |
| Homo sapiens | NCOA2 | NCOA2 | indeterminate | Transcriptional coactivator of steroid hormone receptors | 9238002 8670870 |
| Danio rerio | ncoa2 | Ncoa2 | indeterminate | Possible regulator of hematopoiesis Transcriptional coactivator of steroid hormone receptors |
18295965 18248177 |
| Mus musculus | Ncoa3 | NCOA3 | indeterminate | Transcriptional coactivator of steroid hormone receptors Important for hearing Regulates adipogenesis hematopoiesis Inflammation |
33326993 9765300 |
| Homo sapiens | NCOA3 | NCOA3 | indeterminate | Transcriptional coactivator of steroid hormone receptors Mutation associated with progressive hearing loss |
33326993 9765300 |
| Danio rerio | ncoa3 | Ncoa3 | indeterminate | Development and function of otoliths Proposed trancriptional coactivator | 33326993 |
| Mus musculus | Npas1 | NPAS1 | I | Neural development Behavior |
15347806 9012850 28499489 |
| Homo sapiens | NPAS1 | NPAS1 | I | Neuronal devleopment Regulates genes involved in psychiatric diseases |
9012850 28499489 |
| Danio rerio | npas1 | Npas1 | I | Expressed in adult telencephalon Speculated to be involved in neural development |
25556858 |
| Mus musculus | Npas2 | NPAS2 | I | Circadian rhythm regulation | 11441147 26895328 11163178 17417633 |
| Homo sapiens | NPAS2 | NPAS2 | I | Circadian rhythm regulation Mutation associated with nonobstructive azoospermia |
11441147 11163178 25956372 |
| Danio rerio | npas2 | Npas2 | I | Not characterized | none |
| Mus musculus | Npas3 | NPAS3 | I | Neural development behavior Lung development and function |
15347806 28499489 19581591 |
| Homo sapiens | NPAS3 | NPAS3 | I | Neural development Mutations associated with schizophrenia |
12746393 21709683 22228753 15924306 |
| Danio rerio | npas3 | Npas3 | I | Insufficent data Speculated to be involved in neuronal development |
- |
| Mus musculus | Npas4 | NPAS4 | I | Synaptic plasticity Memory |
24201284 22194569 18815592 |
| Homo sapiens | NPAS4 | NPAS4 | I | Variants associated with intellectual disability | 33758288 24465693 |
| Danio rerio | npas4a | Npas4a | I | Forebrain development Angiogenesis of intersegmental vessicles |
25538572 28082451 |
| Danio rerio | npas4b | Npas4b | I | Angiogenesis of intersegmental vessicles | 28082451 |
| Danio rerio | npas4l | Npas4l | I | Master regulator of hemato-vascular specification Formation of lens cataract |
27411634 7588049 30861003 |
| Drosophila melanogaster | sim | Single-minded | I | Midline central nervous system development Axonal extension |
3345560 3345559 2242162 1760843 16439478 |
| Mus musculus | Sim1 | SIM1 | I | Neuronal development Hypothalamus development and function Obesity |
9784500 16291793 12947113 10587584 |
| Homo sapiens | SIM1 | SIM1 | I | Obesity Neuroendocrine development |
10587584 16924270 33434169 |
| Danio rerio | sim1a | Sim1a | I | Hypothalamus development and function Axonal guidance |
19234064 23222439 16691572 |
| Danio rerio | sim1b | Sim1b | I | Hypothalamus development and function | 19234064 16691572 |
| Mus musculus | Sim2 | SIM1 | I | Development and function of neuroendocrine cells Axon guidance Overexpression causes Down syndrome phenotypes Growth and integrity of skeleton |
14988428 12024028 16291793 10400987 10915774 |
| Homo sapiens | SIM2 | SIM2 | I | Promotes glioblastoma cell invasion Part of Down syndrome critical region on chromosome 21 |
7647800 7568099 20448453 15946822 |
| Danio rerio | sim2 | Sim2 | I | Not characterized | none |
| Drosophila melanogaster | sima | Similar | I | Hypoxic response Trachea development Ortholog of human HIF1A |
12215541 19285057 |
| Drosophila melanogaster | ss | Spineless | I | Distal limb formation Mutants have reduced sensory bristles Ortholog of human AHR |
10433921 17084833 9573046 |
| Drosophila melanogaster | tgo | Tango | II | Neuronal devleopment Glial migration Trachea development Limb formation Coregulator of class I genes Ortholog of human ARNT/ARNT2 |
8557198 10433921 9409674 |
| Drosophila melanogaster | trh | Trachealess | I | Development of salivary duct Development of trachea distal limb Development Most similar to human NPAS1, NPAS3 |
17187773 8557198 |