SESN1

Summary

SESN1 (sestrin 1, HGNC:21595) is a protein-coding gene on chromosome 6q21, encoding Sestrin-1 (Q9Y6P5). Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex.

This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the cellular response to DNA damage and oxidative stress. The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded protein also plays a critical role in antioxidant defense by regenerating overoxidized peroxiredoxins, and the expression of this gene is a potential marker for exposure to radiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 27244 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_014454

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21595
Approved symbol	SESN1
Name	sestrin 1
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	SEST1, PA26
Ensembl gene	ENSG00000080546
Ensembl biotype	protein_coding
OMIM	606103
Entrez	27244

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000302071, ENST00000356644, ENST00000368971, ENST00000436639, ENST00000517548, ENST00000520364, ENST00000523632, ENST00000885410

RefSeq mRNA: 3 — MANE Select: NM_014454 NM_001199933, NM_001199934, NM_014454

CCDS: CCDS5070, CCDS56444, CCDS56445

Canonical transcript exons

ENST00000436639 — 10 exons

Exon	Start	End
ENSE00000800309	109000491	109000673
ENSE00000800312	108992787	108992899
ENSE00000800315	108988543	108988687
ENSE00000800316	108984309	108987630
ENSE00001126902	108998513	108998755
ENSE00001750966	109093795	109094846
ENSE00003618236	108990645	108990835
ENSE00003651213	108994462	108994609
ENSE00003663229	109002278	109002343
ENSE00003679639	109001288	109001488

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.0142 / max 312.3710, expressed in 1803 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74972	19.6609	1741
74979	1.6537	1041
74977	0.7984	251
74978	0.7338	292
74981	0.5401	261
74980	0.3375	168
74975	0.1844	70
74976	0.0724	25
74974	0.0205	8
74971	0.0125	6

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.58	gold quality
diaphragm	UBERON:0001103	97.52	gold quality
gluteal muscle	UBERON:0002000	96.99	gold quality
gastrocnemius	UBERON:0001388	96.91	gold quality
muscle of leg	UBERON:0001383	96.58	gold quality
biceps brachii	UBERON:0001507	96.48	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.42	gold quality
triceps brachii	UBERON:0001509	96.30	gold quality
muscle organ	UBERON:0001630	96.14	gold quality
skeletal muscle organ	UBERON:0014892	96.14	gold quality
right ovary	UBERON:0002118	95.87	gold quality
mucosa of stomach	UBERON:0001199	95.68	gold quality
left ovary	UBERON:0002119	95.49	gold quality
vastus lateralis	UBERON:0001379	95.41	gold quality
right uterine tube	UBERON:0001302	95.39	gold quality
skeletal muscle tissue	UBERON:0001134	95.34	gold quality
quadriceps femoris	UBERON:0001377	94.46	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.42	gold quality
skin of abdomen	UBERON:0001416	94.10	gold quality
body of tongue	UBERON:0011876	93.96	gold quality
right lung	UBERON:0002167	93.90	gold quality
middle temporal gyrus	UBERON:0002771	93.85	gold quality
right testis	UBERON:0004534	93.55	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.48	gold quality
ovary	UBERON:0000992	93.39	gold quality
fundus of stomach	UBERON:0001160	93.32	gold quality
cerebellar hemisphere	UBERON:0002245	93.18	gold quality
cerebellar cortex	UBERON:0002129	93.17	gold quality
body of pancreas	UBERON:0001150	93.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-99795	yes	687.19
E-MTAB-6911	yes	416.95
E-ANND-3	yes	8.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, PPARG, TP53

miRNA regulators (miRDB)

85 targeting SESN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798

Literature-anchored findings (GeneRIF, showing 20)

• PA26 mutations are an infrequent cause of heterotaxia (situs inversus) in humans. (PMID:12607115)
• results show that sestrins, a family of proteins whose expression is modulated by p53, are required for regeneration of peroxiredoxins containing Cys-SO(2)H (PMID:15105503)
• Rapamycin may prohibit sestrin1 downregulation through targeting mTORC2 in appeasing low shear stress induced EC oxidative apoptosis (PMID:24587596)
• this study shows that sestrin1 genetic ablation results in broad reconstitution of immune function in stressed T cells and enhanced vaccine responsiveness in old mice (PMID:28114291)
• The antitumor efficacy of pharmacological EZH2 inhibition depends on SESTRIN1, indicating that mTORC1 control is a critical function of EZH2 in lymphoma. (PMID:28659443)
• Mass spectrometry analysis, western blot and surface plasmon resonance (SPR) of affinity purified sesn1 and sesn2 proteins confirmed their identity; biophysical characteristics were observed using circular dichroism (CD) showing that sesn1 and sesn2 have a predominant a-helical structure. (PMID:28707664)
• Study shows that SESN1 mRNA, UHRF1BP11 mRNA and miRNA-377-3p levels are prognostically relevant in human papillomavirus-negative head and neck squamous cell carcinoma patients. (PMID:28886272)
• mRNA expression of SESN1 was upregulated in older men. (PMID:29751091)
• identified new interactions between miR-200 and the oxidative stress response SESN proteins that affect anoikis resistance in human endometrial cancer cells. (PMID:31073887)
• Sestrin expression decreases during inactivity and its genetic deficiency exacerbates muscle wasting; conversely, sestrin overexpression suffices to prevent atrophy. This protection occurs through mTORC1 inhibition, which upregulates autophagy, and AKT activation, which in turn inhibits FoxO-regulated ubiquitin-proteasome-mediated proteolysis. Sestrin protects muscles against aging-induced atrophy(sarcopenia). (PMID:31929511)
• Integrating Mouse and Human Genetic Data to Move beyond GWAS and Identify Causal Genes in Cholesterol Metabolism. (PMID:32197071)
• Circulating Sestrin Levels Are Increased in Hypertension Patients. (PMID:32626541)
• Inhibition of sestrin 1 alleviates polycystic ovary syndrome by decreasing autophagy. (PMID:33883304)
• The functions and roles of sestrins in regulating human diseases. (PMID:34979914)
• Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes. (PMID:35162104)
• SESN1 attenuates the OxLDLinduced inflammation, apoptosis and endothelialmesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling. (PMID:35293601)
• SESN1, negatively regulated by miR-377-3p, suppresses invasive growth of head and neck squamous cell carcinoma by interaction with SMAD3. (PMID:35622213)
• SESN1 is a FOXO3 effector that counteracts human skeletal muscle ageing. (PMID:37199024)
• Metformin Caused Radiosensitivity of Breast Cancer Cells through the Expression Modulation of miR-21-5p/SESN1axis. (PMID:38019229)
• IGF2BP3 stabilizes SESN1 mRNA to mitigate oxidized low-density lipoprotein-induced oxidative stress and endothelial dysfunction in human umbilical vein endothelial cells by activating Nrf2 signaling. (PMID:38460759)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sesn1	ENSDARG00000020693
mus_musculus	Sesn1	ENSMUSG00000038332
rattus_norvegicus	Sesn1	ENSRNOG00000000302
drosophila_melanogaster	Sesn	FBGN0034897
caenorhabditis_elegans	sesn-1	WBGENE00022279

Paralogs (2): SESN2 (ENSG00000130766), SESN3 (ENSG00000149212)

Protein

Protein identifiers

Sestrin-1 — Q9Y6P5 (reviewed: Q9Y6P5)

Alternative names: p53-regulated protein PA26

All UniProt accessions (1): Q9Y6P5

UniProt curated annotations — full annotation on UniProt →

Function. Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway. This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses. May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1. Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein. Was originally reported to contribute to oxidative stress resistance by reducing PRDX1. However, this could not be confirmed.

Subunit / interactions. Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by leucine. Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them. Interacts with KEAP1, RBX1 and SQSTM1; in the SQSTM1-dependent autophagic degradation of KEAP1. May interact with PRDX1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Widely expressed.

Domain organisation. The N-terminal domain may have an alkylhydroperoxide reductase activity. The C-terminal domain mediates interaction with GATOR2 through which it regulates TORC1 signaling.

Induction. Isoform T2 and isoform T3 are induced by genotoxic stress (UV, gamma-irradiation and cytotoxic drugs) in a p53/TP53-dependent manner. Isoform T1 is not induced by p53/TP53.

Similarity. Belongs to the sestrin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y6P5-1	T2	yes
Q9Y6P5-2	T1
Q9Y6P5-3	T3

RefSeq proteins (3): NP_001186862, NP_001186863, NP_055269* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006730	Sestrin	Family
IPR029032	AhpD-like	Homologous_superfamily

Pfam: PF04636

Catalyzed reactions (Rhea), 1 shown:

• a hydroperoxide + L-cysteinyl-[protein] = S-hydroxy-L-cysteinyl-[protein] + an alcohol (RHEA:67124)

UniProt features (13 total): binding site 3, region of interest 2, splice variant 2, modified residue 2, chain 1, sequence variant 1, mutagenesis site 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6P5-F1	84.25	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 130 (cysteine sulfenic acid (-soh) intermediate)

Ligand- & substrate-binding residues (3): 386–389; 398; 463

Post-translational modifications (2): 293, 314

Mutagenesis-validated functional residues (1):

Position	Phenotype
130	loss of the ability to decrease intracellular reactive oxygen species.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-9755511	KEAP1-NFE2L2 pathway
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711097	Cellular response to starvation
R-HSA-9711123	Cellular response to chemical stress

MSigDB gene sets: 412 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_RESPONSE_TO_ACID_CHEMICAL, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MACROAUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (12): positive regulation of macroautophagy (GO:0016239), negative regulation of cell growth (GO:0030308), cellular response to amino acid starvation (GO:0034198), cellular response to glucose starvation (GO:0042149), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), cellular response to L-leucine (GO:0071233), reactive oxygen species metabolic process (GO:0072593), cellular oxidant detoxification (GO:0098869), regulation of response to reactive oxygen species (GO:1901031), negative regulation of TORC1 signaling (GO:1904262), cellular response to leucine starvation (GO:1990253), cellular response to amino acid stimulus (GO:0071230)

GO Molecular Function (4): oxidoreductase activity, acting on peroxide as acceptor (GO:0016684), L-leucine binding (GO:0070728), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), GATOR2 complex (GO:0061700)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Cellular responses to stress	2
Cellular response to starvation	1
Cellular response to chemical stress	1
Transcriptional Regulation by TP53	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular response to starvation	2
positive regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
response to amino acid starvation	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of intracellular signal transduction	1
response to L-leucine	1
cellular response to amino acid stimulus	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
metabolic process	1
cellular detoxification	1
response to reactive oxygen species	1
regulation of response to oxidative stress	1
negative regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
cellular response to amino acid starvation	1
response to amino acid	1
cellular response to acid chemical	1
oxidoreductase activity	1
amino acid binding	1
carboxylic acid binding	1
cation binding	1
binding	1
catalytic activity	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
protein-containing complex	1
Seh1-associated complex	1

Protein interactions and networks

STRING

978 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SESN1	TSC2	P49815	886
SESN1	CACNA2D2	Q9NY47	828
SESN1	TP53	P04637	760
SESN1	GADD45G	O95257	746
SESN1	WDR24	Q96S15	724
SESN1	GADD45A	P24522	698
SESN1	TP53I3	Q53FA7	642
SESN1	RBX1	P62877	638
SESN1	SEH1L	Q96EE3	625
SESN1	KEAP1	Q14145	617
SESN1	TSC1	Q92574	605
SESN1	CASTOR1	Q8WTX7	588
SESN1	DRAM1	Q8N682	573
SESN1	ZMAT3	Q9HA38	545
SESN1	RRAGB	Q5VZM2	544
SESN1	RRAGA	Q7L523	544

IntAct

6 interactions, top by confidence:

A	B	Type	Score
WDR24	SESN2	psi-mi:“MI:0914”(association)	0.890
MIOS	SEC13	psi-mi:“MI:0914”(association)	0.790
SESN1	SQSTM1	psi-mi:“MI:0915”(physical association)	0.400
SESN1	Rbx1	psi-mi:“MI:0915”(physical association)	0.400
KEAP1	SESN1	psi-mi:“MI:0915”(physical association)	0.400
SESN1	WDR59	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (13): SESN1 (Affinity Capture-RNA), SESN1 (Affinity Capture-RNA), SESN1 (Affinity Capture-MS), WDR24 (Reconstituted Complex), MIOS (Reconstituted Complex), SESN1 (Affinity Capture-MS), SESN1 (Affinity Capture-MS), SESN1 (Affinity Capture-RNA), SESN1 (Affinity Capture-RNA), PRDX1 (Affinity Capture-Western), SQSTM1 (Affinity Capture-Western), RBX1 (Affinity Capture-Western), KEAP1 (Affinity Capture-Western)

ESM2 similar proteins: A0JM23, A4IGD2, A5PKL6, A6NHR9, A6QQZ0, D3ZAT9, F1QWA8, O35099, O88741, O94952, P0CI65, P58005, Q29RL0, Q2TBQ7, Q3U213, Q3UMF9, Q4R6P7, Q4R6Y8, Q5E9N5, Q5F204, Q5HYI7, Q5I0G3, Q5IH14, Q5R5S1, Q5R9R1, Q5RL51, Q5TGI0, Q60649, Q6AZT7, Q6DDI6, Q6DDT5, Q6DEY8, Q6NXY1, Q6YXW6, Q7TNH6, Q7Z494, Q8NBP0, Q8NEC7, Q8TB36, Q94E75

Diamond homologs: P58003, P58004, P58005, P58006, P58043, Q4R6P7, Q54WU6, Q58CN8, Q5RCB4, Q9CYP7, Q9W1K5, Q9Y6P5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SESN1	“down-regulates activity”	GATOR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

8 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1958 predictions. Top by Δscore:

Variant	Effect	Δscore
6:108988538:CATA:C	donor_loss	1.0000
6:108988539:ATAC:A	donor_loss	1.0000
6:108988540:TA:T	donor_loss	1.0000
6:108988542:CCTT:C	donor_gain	1.0000
6:108988683:CATAT:C	acceptor_gain	1.0000
6:108988685:TAT:T	acceptor_gain	1.0000
6:108988685:TATC:T	acceptor_loss	1.0000
6:108988686:AT:A	acceptor_gain	1.0000
6:108988687:TC:T	acceptor_loss	1.0000
6:108988688:C:CA	acceptor_loss	1.0000
6:108988688:C:CC	acceptor_gain	1.0000
6:108988689:T:A	acceptor_loss	1.0000
6:108988691:T:TC	acceptor_gain	1.0000
6:108992781:TTTTA:T	donor_loss	1.0000
6:108992782:TTTAC:T	donor_loss	1.0000
6:108992783:TTA:T	donor_loss	1.0000
6:108992784:TA:T	donor_loss	1.0000
6:108992785:A:C	donor_loss	1.0000
6:108992786:CC:C	donor_loss	1.0000
6:108992897:CAT:C	acceptor_gain	1.0000
6:108992899:TCT:T	acceptor_loss	1.0000
6:108992900:C:CA	acceptor_loss	1.0000
6:108992900:C:CC	acceptor_gain	1.0000
6:108992901:T:A	acceptor_loss	1.0000
6:108992913:CCAT:C	acceptor_gain	1.0000
6:108992914:CAT:C	acceptor_gain	1.0000
6:108992916:T:TC	acceptor_gain	1.0000
6:108994457:CTTAC:C	donor_loss	1.0000
6:108994459:TA:T	donor_loss	1.0000
6:108994460:AC:A	donor_loss	1.0000

AlphaMissense

3682 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:108990651:C:T	G414E	1.000
6:108990687:C:G	R402T	1.000
6:108990824:C:A	W356C	1.000
6:108990824:C:G	W356C	1.000
6:108990826:A:G	W356R	1.000
6:108990826:A:T	W356R	1.000
6:109000517:A:G	W176R	1.000
6:109000517:A:T	W176R	1.000
6:108988547:T:A	E463V	0.999
6:108988633:T:A	K434N	0.999
6:108988633:T:G	K434N	0.999
6:108988652:A:G	L428P	0.999
6:108990651:C:A	G414V	0.999
6:108990652:C:G	G414R	0.999
6:108990652:C:T	G414R	0.999
6:108990686:T:A	R402S	0.999
6:108990686:T:G	R402S	0.999
6:108990687:C:A	R402I	0.999
6:108990813:C:T	G360D	0.999
6:108998728:A:G	W194R	0.999
6:108998728:A:T	W194R	0.999
6:108987584:A:G	L480P	0.998
6:108987602:G:T	A474D	0.998
6:108987603:C:G	A474P	0.998
6:108987617:A:G	L469P	0.998
6:108987623:A:T	V467D	0.998
6:108988559:A:G	F459S	0.998
6:108988671:A:G	Y422H	0.998
6:108990682:C:G	A404P	0.998
6:108990699:G:A	T398I	0.998

dbSNP variants (sampled 300 via entrez): RS1000007652 (6:109066651 A>G), RS1000024959 (6:109020925 A>C), RS1000166344 (6:109042762 T>TG), RS1000166896 (6:109051822 A>G), RS1000167234 (6:109090434 A>G), RS1000193312 (6:109037435 C>A,T), RS1000200575 (6:108988456 A>G), RS1000204637 (6:109037902 A>G), RS1000236559 (6:109087298 C>A,T), RS1000277167 (6:108994812 C>G), RS1000297313 (6:109028562 T>TGC), RS1000297635 (6:109073705 T>C), RS1000328229 (6:109083854 G>A), RS1000344002 (6:109035534 C>CT), RS1000357527 (6:109030062 C>A,G)

Disease associations

OMIM: gene MIM:606103 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001942_10	Prostate cancer	8.000000e-09
GCST004602_115	Mean corpuscular volume	3.000000e-23
GCST008362_158	Birth weight	2.000000e-11
GCST008363_51	Offspring birth weight	2.000000e-09
GCST009391_703	Metabolite levels	2.000000e-06
GCST010042_76	Asthma	1.000000e-08
GCST010043_145	Asthma	3.000000e-10
GCST90002381_159	Eosinophil count	2.000000e-11
GCST90002382_351	Eosinophil percentage of white cells	1.000000e-09
GCST90002390_442	Mean corpuscular hemoglobin	8.000000e-17

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0010356	lysophosphatidylcholine 14:0 measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

100 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects cotreatment, increases expression	8
Cisplatin	affects cotreatment, increases expression, decreases expression, affects expression	7
Aflatoxin B1	affects expression, increases expression	5
sodium arsenite	decreases reaction, increases expression, affects methylation, affects binding, increases reaction (+1 more)	4
Fluorouracil	increases expression, affects reaction, increases reaction	4
Estradiol	affects expression, affects cotreatment, decreases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Formaldehyde	decreases expression, increases expression	2
Hydrogen Peroxide	affects expression, decreases expression, decreases reaction	2
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
Cyclosporine	affects expression, decreases expression	2
Cadmium Chloride	decreases expression	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
chloroacetaldehyde	increases expression	1
myristicin	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
benzo(b)fluoranthene	affects cotreatment, increases expression	1
bisphenol A	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
afimoxifene	decreases expression, decreases reaction	1
cobaltous chloride	increases expression	1
potassium bromate	increases expression	1
brusatol	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.