Sigma-1 receptor

The sigma-1 receptor (σ₁R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor.^[5] In humans, the σ₁ receptor is encoded by the SIGMAR1 gene.^[6][7]

SIGMAR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5HK1, 5HK2
Identifiers
Aliases	SIGMAR1, ALS16, OPRS1, SIG-1R, SR-BP, SR-BP1, SRBP, hSigmaR1, sigma1R, DSMA2, sigma non-opioid intracellular receptor 1
External IDs	OMIM: 601978 MGI: 1195268 HomoloGene: 39965 GeneCards: SIGMAR1
Gene location (Human) Chr. Chromosome 9 (human)^[1] Band 9p13.3 Start 34,634,722 bp^[1] End 34,637,844 bp^[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)^[2] Band 4|4 A5 Start 41,738,493 bp^[2] End 41,756,157 bp^[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver stromal cell of endometrium right coronary artery left uterine tube right adrenal gland canal of the cervix left adrenal gland left coronary artery thoracic aorta ascending aorta Top expressed in left lobe of liver lip yolk sac superior frontal gyrus external carotid artery internal carotid artery white adipose tissue neural tube somite proximal tubule More reference expression data BioGPS n/a
Gene ontology Molecular function G protein-coupled opioid receptor activity identical protein binding signaling receptor activity Cellular component postsynaptic membrane cell projection endoplasmic reticulum membrane membrane growth cone lipid droplet plasma membrane synapse integral component of plasma membrane cell junction nuclear inner membrane nuclear outer membrane nucleus nuclear envelope endoplasmic reticulum integral component of membrane cytoplasmic vesicle postsynaptic density Biological process lipid transport regulation of neuron apoptotic process nervous system development G protein-coupled opioid receptor signaling pathway protein homotrimerization signal transduction cell death in response to hydrogen peroxide Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10280 18391 Ensembl ENSG00000147955 ENSMUSG00000036078 UniProt Q99720 O55242 RefSeq (mRNA) NM_001282205 NM_001282206 NM_001282207 NM_001282208 NM_001282209 NM_005866 NM_147157 NM_147158 NM_147159 NM_147160 NM_011014 NM_001286538 NM_001286539 NM_001286540 NM_001286541 NM_001286542 NM_001286551 NM_001286605 RefSeq (protein) NP_001269134 NP_001269135 NP_001269136 NP_001269137 NP_001269138 NP_005857 NP_671513 NP_001273467 NP_001273468 NP_001273469 NP_001273470 NP_001273471 NP_001273480 NP_001273534 NP_035144 Location (UCSC) Chr 9: 34.63 – 34.64 Mb Chr 4: 41.74 – 41.76 Mb PubMed search ^[3] ^[4]
Wikidata
View/Edit Human View/Edit Mouse

The σ₁ receptor is a transmembrane protein expressed in many different tissue types. It is particularly concentrated in certain regions of the central nervous system.^[8] It has been implicated in several phenomena, including cardiovascular function, schizophrenia, clinical depression, the effects of cocaine abuse, bipolar disorder, and cancer.^[9][10] Much is known about the binding affinity of hundreds of synthetic compounds to the σ₁ receptor.

An endogenous ligand for the σ₁ receptor has yet to be conclusively identified, but tryptaminergic trace amines and neuroactive steroids have been found to activate the receptor.^[11] Especially progesterone, but also testosterone, pregnenolone sulfate, N,N-Dimethyltryptamine (DMT) and dehydroepiandrosterone sulfate (DHEA-S) bind to the σ₁ receptor.^[12]

Characteristics

The σ₁ receptor is defined by its unique pharmacological profile. In 1976 Martin reported that the effects of N-allylnormetazocine (SKF-10,047) could not be due to activity at the μ and κ receptors (named from the first letter of their selective ligands morphine and ketazocine, respectively) and a new type of opioid receptor was proposed; σ (from the first letter of SKF-10,047).^[13] The opioid classification was eventually dropped however resulting from it not possessing the canonical opioid G-protein coupled receptor structure and the receptor was later referred to as simply the σ₁ receptor. It was found to have affinity for the (+)-stereoisomers of several benzomorphans (e.g., (+)-pentazocine and (+)-cyclazocine), as well as various structurally and pharmacologically distinct psychoactive chemicals such as haloperidol and cocaine, and neuroactive steroids like progesterone.^[14] Pharmacological studies with σ₁ agonists often follow a bell-shaped dose-response curve.^[15] Thus care should be taken when designing experiments and choosing doses of ligands.

Structure

The mammalian σ₁ receptor is an integral membrane protein with 223 amino acids.^[16] It shows no homology to other mammalian proteins but strikingly shares 30% sequence identity and 69% similarity with the ERG2 gene product of yeast, which is a C8-C7 sterol isomerase in the ergosterol biosynthetic pathway. Hydropathy analysis of the σ₁ receptor indicates three hydrophobic regions.^[17] A crystal structure of the σ₁ receptor was published in 2016.^[18]

Functions

A variety of specific physiological functions have been attributed to the σ₁ receptor. Chief among these are modulation of Ca²⁺ release, modulation of cardiac myocyte contractility, and inhibition of voltage gated K⁺ channels.^[19] The reasons for these effects are not well understood, even though σ₁ receptors have been linked circumstantially to a wide variety of signal transduction pathways. Links between σ₁ receptors and G-proteins have been suggested such as σ₁ receptor antagonists showing GTP-sensitive high-affinity binding;^[20] there is also, however, some evidence against a G-protein coupled hypothesis.^[21] The σ₁ receptor has been shown to appear in a complex with voltage gated K⁺ channels (K_v1.4 and K_v1.5), leading to the idea that σ₁ receptors are auxiliary subunits.^[22] σ₁ receptors apparently co-localize with IP₃ receptors on the endoplasmic reticulum^[23] where they may be involved in preventing endoplasmic reticulum stress in neurodegenerative diseases.^[24] Also, σ₁ receptors have been shown to appear in galactoceramide enriched domains at the endoplasmic reticulum of mature oligodendrocytes.^[25] The wide scope and effect of ligand binding on σ₁ receptors has led some to believe that σ₁ receptors are intracellular signal transduction amplifiers.^[14]

Recently, σ₁R has been implicated in autophagosome formation ^[26] and maturation.^[27] Autophagy is a broad homeostatic, metabolic, cytoplasmic quality control, and metabolic process affecting many functions in the cell.^[28] σ₁R is targeted by the nsp6 protein of SARS-CoV-2^[29][26] to inhibit autophagosome formation ^[26] as a process competing with the coronavirus for cellular endomembranes that the virus needs for its own replication. This along with the observed beneficial effects of sigma-1 receptor agonist and SSRI fluvoxamine in patients with SARS-COV-2 infection^[30] has led to the hypothesis that the sigma-1 receptor could be a target for the treatment of SARS-COV-2.^[31]

There has been much interest in the sigma-1 receptor and its role in age-related neurodegenerative diseases such as Alzheimer's disease. During healthy ageing, the density of sigma-1 receptors has been to increase. However, in diseases such as Alzheimer's disease, there appears to be a reduction in sigma-1 receptor expression. It has been suggested that targeting the sigma-1 receptor along with other receptors could increase neuron survival and function in neurodegenerative disease.^[15] The activation of autophagy has also been suggested as a downstream mechanism linked to sigma-1 receptor activation.^[32]

Knockout mice

σ₁ receptor knockout mice were created in 2003 to study the effects of endogenous DMT. Strangely, the mice demonstrated no overt phenotype.^[33] As expected, however, they did lack locomotor response to the σ ligand (+)-SKF-10,047 and displayed reduced response to formalin induced pain. Speculation has focused on the ability of other receptors in the σ family (e.g., σ₂, with similar binding properties) to compensate for the lack of σ₁ receptor.^[33]

Clinical significance

Mutations in the SIGMAR1 gene have been associated with distal spinal muscular atrophy type 2.^[34]

Ligands

The following ligands have high affinity for the σ₁ receptor and possess high binding selectivity over the subtype σ₂:

Agonists:

• PRE-084
• Blarcamesine
• Donepezil
• Fluvoxamine
• Fluoxetine
• Citalopram
• Amitriptyline
• Cocaine
• L-687,384
• Cutamesine
• Dipentylamine and its hydrochloride salt (dipentylammonium chloride)^[35][36]
• Dextromethorphan
• Dimethyltryptamine
• (+)-pentazocine (the "unnatural" enantiomer, which lacks affinity for the μ-opioid and κ-opioid receptors.)
• Opipramol

Antagonists:

• Methamphetamine
• Selegiline
• D-Deprenyl
• Sertraline
• S1RA
• FTC-146
• 1-benzyl-6′-methoxy-6′,7′-dihydrospiro[piperidine-4,4′-thieno[3.2-c]pyran]: putative antagonist, selective against 5-HT_1A, 5-HT₆, 5-HT₇, α_1A and α₂ adrenergic, and NMDA receptors^[37]
• NE-100

Positive allosteric modulators (PAMs):

• Methylphenylpiracetam^{[38][better source needed]}
• SOMCL-668^[39]

Uncategorized:

• 4-IPBS
• PD 144418
• Spipethiane
• RHL-033
• 3-[[1-[(4-chlorophenyl)methyl]-4-piperidyl]methyl]-1,3-benzoxazol-2-one: very high affinity and subtype selectivity^[40]
• 1'-[(4-fluorophenyl)methyl]spiro[1H-isobenzofuran-3,4'-piperidine]^[41]
• 1'-benzyl-6-methoxy-1-phenyl-spiro[6H-furo[3,4-c]pyrazole-4,4'-piperidine]^[42]
• (−)-(S)-4-methyl-1-[2-(4-chlorophenoxy)-1-methylethyl]piperidine^[43]

Agents exist that have high σ₁ affinity but either lack subtype selectivity or have high affinity at other binding sites, thus being more or less dirty/multifunctional, like haloperidol. Furthermore, there is a wide range of agents with an at least moderate σ₁ involvement in their binding profile.^[44][45]

See also

• Sigma-2 receptor

References

1. GRCh38: Ensembl release 89: ENSG00000147955 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000036078 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hayashi T, Su TP (November 2007). "Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival". Cell. 131 (3): 596–610. doi:10.1016/j.cell.2007.08.036. PMID 17981125. S2CID 18885068.
6. Kekuda R, Prasad PD, Fei YJ, Leibach FH, Ganapathy V (December 1996). "Cloning and functional expression of the human type 1 sigma receptor (hSigmaR1)". Biochemical and Biophysical Research Communications. 229 (2): 553–558. doi:10.1006/bbrc.1996.1842. PMID 8954936.
7. Prasad PD, Li HW, Fei YJ, Ganapathy ME, Fujita T, Plumley LH, et al. (February 1998). "Exon-intron structure, analysis of promoter region, and chromosomal localization of the human type 1 sigma receptor gene". Journal of Neurochemistry. 70 (2): 443–451. doi:10.1046/j.1471-4159.1998.70020443.x. PMID 9453537. S2CID 22305479.
8. Weissman AD, Su TP, Hedreen JC, London ED (October 1988). "Sigma receptors in post-mortem human brains". The Journal of Pharmacology and Experimental Therapeutics. 247 (1): 29–33. PMID 2845055.
9. Guitart X, Codony X, Monroy X (July 2004). "Sigma receptors: biology and therapeutic potential". Psychopharmacology. 174 (3): 301–319. doi:10.1007/s00213-004-1920-9. PMID 15197533. S2CID 23606712.
10. Zhang H, Cuevas J (June 2005). "sigma Receptor activation blocks potassium channels and depresses neuroexcitability in rat intracardiac neurons". The Journal of Pharmacology and Experimental Therapeutics. 313 (3): 1387–1396. doi:10.1124/jpet.105.084152. PMID 15764734. S2CID 9704436.
11. Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, Jackson MB, Ruoho AE (February 2009). "The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator". Science. 323 (5916): 934–937. Bibcode:2009Sci...323..934F. doi:10.1126/science.1166127. PMC 2947205. PMID 19213917.
12. Hayashi T, Su TP (2004). "Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders". CNS Drugs. 18 (5): 269–284. doi:10.2165/00023210-200418050-00001. PMID 15089113. S2CID 72726251.
13. Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE (June 1976). "The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog". The Journal of Pharmacology and Experimental Therapeutics. 197 (3): 517–532. PMID 945347.
14. Su TP, Hayashi T (October 2003). "Understanding the molecular mechanism of sigma-1 receptors: towards a hypothesis that sigma-1 receptors are intracellular amplifiers for signal transduction". Current Medicinal Chemistry. 10 (20): 2073–2080. doi:10.2174/0929867033456783. PMID 12871086.
15. Brimson JM, Brimson S, Chomchoei C, Tencomnao T (October 2020). "Using sigma-ligands as part of a multi-receptor approach to target diseases of the brain". Expert Opinion on Therapeutic Targets. 24 (10): 1009–1028. doi:10.1080/14728222.2020.1805435. PMID 32746649. S2CID 225218231.
16. Hanner M, Moebius FF, Flandorfer A, Knaus HG, Striessnig J, Kempner E, Glossmann H (July 1996). "Purification, molecular cloning, and expression of the mammalian sigma1-binding site". Proceedings of the National Academy of Sciences of the United States of America. 93 (15): 8072–8077. Bibcode:1996PNAS...93.8072H. doi:10.1073/pnas.93.15.8072. PMC 38877. PMID 8755605.
17. Moebius FF, Striessnig J, Glossmann H (March 1997). "The mysteries of sigma receptors: new family members reveal a role in cholesterol synthesis". Trends in Pharmacological Sciences. 18 (3): 67–70. doi:10.1016/s0165-6147(96)01037-1. PMID 9133773.
18. Schmidt HR, Zheng S, Gurpinar E, Koehl A, Manglik A, Kruse AC (April 2016). "Crystal structure of the human σ₁ receptor". Nature. 532 (7600): 527–530. Bibcode:2016Natur.532..527S. doi:10.1038/nature17391. PMC 5550834. PMID 27042935.
19. Monassier L, Bousquet P (February 2002). "Sigma receptors: from discovery to highlights of their implications in the cardiovascular system". Fundamental & Clinical Pharmacology. 16 (1): 1–8. doi:10.1046/j.1472-8206.2002.00063.x. PMID 11903506. S2CID 27932111.
20. Brimson JM, Brown CA, Safrany ST (September 2011). "Antagonists show GTP-sensitive high-affinity binding to the sigma-1 receptor". British Journal of Pharmacology. 164 (2b): 772–780. doi:10.1111/j.1476-5381.2011.01417.x. PMC 3188898. PMID 21486275.
21. Hong W, Werling LL (November 2000). "Evidence that the sigma(1) receptor is not directly coupled to G proteins". European Journal of Pharmacology. 408 (2): 117–125. doi:10.1016/S0014-2999(00)00774-3. PMID 11080517.
22. Lupardus PJ, Wilke RA, Aydar E, Palmer CP, Chen Y, Ruoho AE, Jackson MB (August 2000). "Membrane-delimited coupling between sigma receptors and K+ channels in rat neurohypophysial terminals requires neither G-protein nor ATP". The Journal of Physiology. 526 Pt 3 (3): 527–539. doi:10.1111/j.1469-7793.2000.00527.x. PMC 2270035. PMID 10922005.
23. Hayashi T, Su TP (January 2001). "Regulating ankyrin dynamics: Roles of sigma-1 receptors". Proceedings of the National Academy of Sciences of the United States of America. 98 (2): 491–496. doi:10.1073/pnas.021413698. PMC 14614. PMID 11149946.
24. Brimson JM, Safrany ST, Qassam H, Tencomnao T (August 2018). "Dipentylammonium Binds to the Sigma-1 Receptor and Protects Against Glutamate Toxicity, Attenuates Dopamine Toxicity and Potentiates Neurite Outgrowth in Various Cultured Cell Lines". Neurotoxicity Research. 34 (2): 263–272. doi:10.1007/s12640-018-9883-5. PMID 29589276. S2CID 4378593.
25. Hayashi T, Su TP (October 2004). "Sigma-1 receptors at galactosylceramide-enriched lipid microdomains regulate oligodendrocyte differentiation". Proceedings of the National Academy of Sciences of the United States of America. 101 (41): 14949–14954. Bibcode:2004PNAS..10114949H. doi:10.1073/pnas.0402890101. PMC 522002. PMID 15466698.
26. Kumar S, Javed R, Mudd M, Pallikkuth S, Lidke KA, Jain A, et al. (November 2021). "Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes". Cell. 184 (24): 5950–5969.e22. doi:10.1016/j.cell.2021.10.017. PMC 8616855. PMID 34741801.
27. Yang H, Shen H, Li J, Guo LW (September 2019). "SIGMAR1/Sigma-1 receptor ablation impairs autophagosome clearance". Autophagy. 15 (9): 1539–1557. doi:10.1080/15548627.2019.1586248. PMC 6693456. PMID 30871407.
28. Levine B, Kroemer G (January 2019). "Biological Functions of Autophagy Genes: A Disease Perspective". Cell. 176 (1–2): 11–42. doi:10.1016/j.cell.2018.09.048. PMC 6347410. PMID 30633901.
29. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. (July 2020). "A SARS-CoV-2 protein interaction map reveals targets for drug repurposing". Nature. 583 (7816): 459–468. Bibcode:2020Natur.583..459G. doi:10.1038/s41586-020-2286-9. PMC 7431030. PMID 32353859.
30. Lenze EJ, Mattar C, Zorumski CF, Stevens A, Schweiger J, Nicol GE, et al. (December 2020). "Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial". JAMA. 324 (22): 2292–2300. doi:10.1001/jama.2020.22760. PMC 7662481. PMID 33180097.
31. Brimson JM, Prasanth MI, Malar DS, Brimson S, Thitilertdecha P, Tencomnao T (June 2021). "Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy". Expert Opinion on Therapeutic Targets. 25 (6): 435–449. doi:10.1080/14728222.2021.1952987. PMC 8290373. PMID 34236922.
32. Prasanth MI, Malar DS, Tencomnao T, Brimson JM (May 2021). "The emerging role of the sigma-1 receptor in autophagy: hand-in-hand targets for the treatment of Alzheimer's". Expert Opinion on Therapeutic Targets. 25 (5): 401–414. doi:10.1080/14728222.2021.1939681. PMID 34110944. S2CID 235402107.
33. Langa F, Codony X, Tovar V, Lavado A, Giménez E, Cozar P, et al. (October 2003). "Generation and phenotypic analysis of sigma receptor type I (sigma 1) knockout mice". The European Journal of Neuroscience. 18 (8): 2188–2196. doi:10.1046/j.1460-9568.2003.02950.x. PMID 14622179. S2CID 85814812.
34. Li X, Hu Z, Liu L, Xie Y, Zhan Y, Zi X, et al. (June 2015). "A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy". Neurology. 84 (24): 2430–2437. doi:10.1212/WNL.0000000000001680. PMID 26078401. S2CID 22155027.
35. Brimson JM, Safrany ST, Qassam H, Tencomnao T (August 2018). "Dipentylammonium Binds to the Sigma-1 Receptor and Protects Against Glutamate Toxicity, Attenuates Dopamine Toxicity and Potentiates Neurite Outgrowth in Various Cultured Cell Lines". Neurotoxicity Research. 34 (2): 263–272. doi:10.1007/s12640-018-9883-5. PMID 29589276. S2CID 4378593.
36. Brimson JM, Akula KK, Abbas H, Ferry DR, Kulkarni SK, Russell ST, et al. (June 2020). "Simple ammonium salts acting on sigma-1 receptors yield potential treatments for cancer and depression". Scientific Reports. 10 (1): 9251. Bibcode:2020NatSR..10.9251B. doi:10.1038/s41598-020-65849-6. PMC 7280195. PMID 32514120.
37. Oberdorf C, Schepmann D, Vela JM, Diaz JL, Holenz J, Wünsch B (October 2008). "Thiophene bioisosteres of spirocyclic sigma receptor ligands. 1. N-substituted spiro[piperidine-4,4'-thieno[3,2-c]pyrans]". Journal of Medicinal Chemistry. 51 (20): 6531–6537. doi:10.1021/jm8007739. PMID 18816044.
38. Vavers E, Zvejniece L, Veinberg G, Svalbe B, Domracheva I, Vilskersts R, Dambrova M (2015). "Novel positive allosteric modulators of sigma-1 receptor". SpringerPlus. 4 (Suppl 1): P51. doi:10.1186/2193-1801-4-S1-P51. PMC 4797911. The R-configuration enantiomers of methylphenylpiracetam are more active positive allosteric modulators of Sigma-1 receptor than S-configuration enantiomers.
39. Wang Y, Guo L, Jiang HF, Zheng LT, Zhang A, Zhen XC (May 2016). "Allosteric Modulation of Sigma-1 Receptors Elicits Rapid Antidepressant Activity". CNS Neuroscience & Therapeutics. 22 (5): 368–377. doi:10.1111/cns.12502. PMC 6492821. PMID 26854125.
40. Zampieri D, Grazia Mamolo M, Laurini E, Zanette C, Florio C, Collina S, et al. (January 2009). "Substituted benzo[d]oxazol-2(3H)-one derivatives with preference for the sigma1 binding site". European Journal of Medicinal Chemistry. 44 (1): 124–130. doi:10.1016/j.ejmech.2008.03.011. PMID 18440098.
41. Grosse Maestrup E, Wiese C, Schepmann D, Hiller A, Fischer S, Scheunemann M, et al. (May 2009). "Synthesis of spirocyclic sigma1 receptor ligands as potential PET radiotracers, structure-affinity relationships and in vitro metabolic stability". Bioorganic & Medicinal Chemistry. 17 (10): 3630–3641. doi:10.1016/j.bmc.2009.03.060. PMID 19394833.
42. Schläger T, Schepmann D, Würthwein EU, Wünsch B (March 2008). "Synthesis and structure-affinity relationships of novel spirocyclic sigma receptor ligands with furopyrazole structure". Bioorganic & Medicinal Chemistry. 16 (6): 2992–3001. doi:10.1016/j.bmc.2007.12.045. PMID 18221879.
43. Berardi F, Loiodice F, Fracchiolla G, Colabufo NA, Perrone R, Tortorella V (May 2003). "Synthesis of chiral 1-[Ω-(4-chlorophenoxy)alkyl]-4-methylpiperidines and their biological evaluation at σ₁, σ₂, and sterol Δ8–Δ7 isomerase sites". Journal of Medicinal Chemistry. 46 (11): 2117–2124. doi:10.1021/jm021014d. PMID 12747784.
44. EP 1787679, Buschman HH, "Use of compounds binding to the sigma receptor for the treatment of diabetes-associated pain", published 23 May 2007, assigned to Esteve Pharmaceuticals SA 
45. Lee IT, Chen S, Schetz JA (January 2008). "An unambiguous assay for the cloned human sigma₁ receptor reveals high affinity interactions with dopamine D₄ receptor selective compounds and a distinct structure-affinity relationship for butyrophenones". European Journal of Pharmacology. 578 (2–3): 123–136. doi:10.1016/j.ejphar.2007.09.020. PMC 2963108. PMID 17961544.

External links

• sigma-1+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• SIGMAR1 human gene location in the UCSC Genome Browser.
• SIGMAR1 human gene details in the UCSC Genome Browser.