Table 1.
Genes encoding for proteins involved in (a) peripheral respiratory chemoreception of the carotid body (CB) and in (b) central respiratory chemoreception. Variants in these genes may restrict the chemoreception in the CB, retrotrapezoid nucleus (RTB) or locus coeruleus (LC), but may also alter the function of other organs.
| Genes | pLI | Description | Function | Other disorders | Source |
|---|---|---|---|---|---|
| (a) Peripheral respiratory chemoreception | |||||
| KCNK9 | 0.9 |
2P-K-channel, member 9 (TASK-3) |
O2/CO2/H+ in the CB |
Epilepsy | F: Kim (2009)16 |
| KCNK3 | 0.9 |
2P-K-channel, member 3 (TASK-1) |
O2/CO2/H+ in the CB |
Primary pulmonary hypertension |
F: Kim (2009)16 OD: Ma (2013)56 |
| OR51E2 | 0 | Olfactory receptor family 51 subfamily E member 2 |
O2/CO2/H+ in the CB |
F: Chang (2015)44 | |
| KCNMA1 | 1 | Calcium-activated K+ channel subfamily M alpha 1 (Maxi-K+) | Peripheral chemoreception | Generalized epilepsy, cerebral atrophy, developmental delay |
F: Gomez-Nino (2009)48 OD: Du W (2005)49 |
| NDUFS2 | 0 |
NAD: ubiquinone oxidoreductase core subunit S2 |
Peripheral chemoreception | Mitochondrial complex I deficiency, leukodystrophy |
F: Fernandez (2015)20 OD: Schuelke (1999)59 |
| (b) Central respiratory chemoreception | |||||
| KCNK5 | 0.33 |
2P-K-channel, member 5 (TASK-2) |
CO2 chemoreception RTN | Renal acidosis |
F: Gestreau (2010)22 OD: Warth (2004)57 |
| GPR4 | 0.1 |
G-protein-coupled receptor 4 (GPR4) |
CO2 chemoreception RTN | Intestinal inflammation |
F: Kumar (2015)28 OD: Wang (2018)58 |
| KCNJ16 | 0 |
Inwardly rectifying K+ channel 5.1 (Kir5.1) |
CO2 chemoreception LC | Renal acidosis |
F: D’Adamo (2011)30 OD: Puissant (2019)54 |
| PHOX2B | 0.94 |
Paired-like homeobox 2B (PHOX2B) |
CO2 chemoreception RTN brain development | CCHS | F: Amiel (2003)25 |
| ATOH1 | 0.02 |
Atonal homolog 1 (ATOH1) |
CO2 chemoreception RTN brain development | F: Ruffault (2015)24 | |
| MECP2 | 0.89 | Methyl-CpG binding protein 2 (MECP2) | CO2 chemoreception in LC brain development |
Rett-syndrome (epileptic seizures) |
F: Zhang (2010)29 |
TASK-1 + 3 Twik (Tandem of P-domains in a weakly inward rectifying K+ channel)-related acid-sensitive potassium channels.
RTN retrotrapezoid nucleus, LC locus coeruleus, CCHS central congenital hypoventilation syndrome, OD other disorder, F function, pLI Probability of being loss-of-function intolerance from the Genome Aggregation Database (gnomAD) browser.36 pLI ≥ 0.9 extremely loss-of-function intolerant genes (printed in bold).