MSRA

Summary

MSRA (methionine sulfoxide reductase A, HGNC:7377) is a protein-coding gene on chromosome 8p23.1, encoding Mitochondrial peptide methionine sulfoxide reductase (Q9UJ68). Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine.

This gene encodes a ubiquitous and highly conserved protein that carries out the enzymatic reduction of methionine sulfoxide to methionine. Human and animal studies have shown the highest levels of expression in kidney and nervous tissue. The protein functions in the repair of oxidatively damaged proteins to restore biological activity. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4482 — RefSeq curated summary.

At a glance

• GWAS associations: 195
• Clinical variants (ClinVar): 89 total — 1 likely-pathogenic
• MANE Select transcript: NM_012331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7377
Approved symbol	MSRA
Name	methionine sulfoxide reductase A
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175806
Ensembl biotype	protein_coding
OMIM	601250
Entrez	4482

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 17 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000317173, ENST00000382490, ENST00000441698, ENST00000517594, ENST00000518255, ENST00000521209, ENST00000521686, ENST00000522907, ENST00000523637, ENST00000528246, ENST00000897531, ENST00000897532, ENST00000897533, ENST00000897534, ENST00000897535, ENST00000897536, ENST00000897537, ENST00000897538, ENST00000897539

RefSeq mRNA: 4 — MANE Select: NM_012331 NM_001135670, NM_001135671, NM_001199729, NM_012331

CCDS: CCDS47798, CCDS47799, CCDS56522, CCDS5975

Canonical transcript exons

ENST00000317173 — 6 exons

Exon	Start	End
ENSE00001215045	10319883	10319989
ENSE00001256673	10054292	10054658
ENSE00001831469	10428148	10428891
ENSE00003603283	10301534	10301638
ENSE00003642608	10207833	10207901
ENSE00003646653	10245104	10245223

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.9446 / max 959.8120, expressed in 1736 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87330	13.3003	1718
87329	3.6961	1374
87341	1.6962	110
87338	0.9613	105
87342	0.4656	92
87339	0.1827	66
87349	0.1485	44
87331	0.1151	36
87340	0.0777	38
87335	0.0587	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.91	gold quality
adult mammalian kidney	UBERON:0000082	95.28	gold quality
right lobe of liver	UBERON:0001114	93.35	gold quality
cerebellar cortex	UBERON:0002129	93.24	gold quality
cerebellum	UBERON:0002037	93.20	gold quality
cerebellar hemisphere	UBERON:0002245	93.20	gold quality
liver	UBERON:0002107	93.16	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.15	gold quality
kidney	UBERON:0002113	92.59	gold quality
bone marrow	UBERON:0002371	91.81	gold quality
apex of heart	UBERON:0002098	91.75	gold quality
bone marrow cell	CL:0002092	91.69	gold quality
blood	UBERON:0000178	91.18	gold quality
corpus callosum	UBERON:0002336	90.57	gold quality
heart left ventricle	UBERON:0002084	90.06	gold quality
duodenum	UBERON:0002114	89.75	gold quality
prefrontal cortex	UBERON:0000451	89.37	gold quality
anterior cingulate cortex	UBERON:0009835	89.29	gold quality
frontal cortex	UBERON:0001870	88.97	gold quality
cortex of kidney	UBERON:0001225	88.85	gold quality
cerebral cortex	UBERON:0000956	88.62	gold quality
right frontal lobe	UBERON:0002810	88.50	gold quality
heart	UBERON:0000948	88.32	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.22	gold quality
Ammon’s horn	UBERON:0001954	88.20	gold quality
monocyte	CL:0000576	88.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.08	gold quality
superior frontal gyrus	UBERON:0002661	88.08	gold quality
leukocyte	CL:0000738	87.96	gold quality
right atrium auricular region	UBERON:0006631	87.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	50.90
E-HCAD-35	yes	28.51
E-ANND-3	yes	7.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO3, KLF6

miRNA regulators (miRDB)

24 targeting MSRA, 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-12121	99.99	66.64	255
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-3167	96.81	67.09	1236
HSA-MIR-4529-3P	96.40	66.46	582
HSA-MIR-6888-5P	95.89	63.78	831
HSA-MIR-6769A-3P	94.91	61.36	412
HSA-MIR-1269A	92.75	64.61	542
HSA-MIR-1269B	92.75	64.73	538
HSA-MIR-1282	91.07	71.26	99

Literature-anchored findings (GeneRIF, showing 37)

• MSRA is down-regulated during cell aging. (PMID:14759519)
• MsrA is present throughout the human lens, where it is likely to defend lens cells and their components against methionine oxidation (PMID:15199188)
• The cloning and characterization of the 5’ promoter region of human msrA are reported. (PMID:16162094)
• MsrA may play an important role in cellular defenses against oxidative stress and in protection against death by limiting the accumulation of oxidative damage to proteins (PMID:16257642)
• showed the expression and function of both sulfoxide reductases together with thioredoxin reductase in the cytosol as well as in the nucleus of epidermal melanocytes which are especially sensitive to reactive oxygen (PMID:16480945)
• MSRA gene on chromosome 8p might possess metastasis suppressor activity in HCC. (PMID:17784942)
• Methionine sulfoxide reductases A and B are seriously affected by hydrogen peroxide accumulation in acute vitiligo. (PMID:17943184)
• this work points towards MSRA as a novel schizophrenia candidate gene (PMID:18506707)
• Retinoic acid regulates transcription of MSRA gene via two distinct promoters via retinoic acid receptors. (PMID:18845237)
• This suggests an important role for an MSRA catalytic antioxidant cycle for protection of the cytoplasmic compartment against oxidative damage. (PMID:19085252)
• almost absent catalase and methionine sulfoxide reductase A and B protein expression in human gray/white scalp hair shafts in association with a functional loss of methionine sulfoxide repair in the entire gray hair follicle (PMID:19237503)
• MSR enzymes are differentially expressed in human skin (PMID:19542914)
• TFAP2B, LYPLAL1 and MSRA are associated with adiposity and fat distribution. (PMID:19557161)
• FOXO3a directly activates the human MsrA promoter in a cell culture system, implying that this could be a conserved mechanism of MsrA regulation. (PMID:19747232)
• protein-specific autoantibody are associated with pulmonary fibrosis and renal vascular damage in systemic sclerosis (PMID:19844733)
• Dual sites of protein initiation control the localization and myristoylation of methionine sulfoxide reductase A (PMID:20368336)
• Our findings indicate that a novel association in the MSRA gene is related to oxidative stress and support the notion of a major role for this process in rheumatoid arthritis. (PMID:20617525)
• reduction of MsrA levels results in increased cell proliferation and extracellular matrix degradation, and consequently in a more aggressive cellular phenotype in breast cancer cells (PMID:20937881)
• Data suggest a critical role for TXNL6 in MsrA repair of essential lens proteins under oxidative stress conditions and that TXNL6 is important for MsrA defense protection against cataract. (PMID:21079812)
• central obesity-associated variants in LYPLAL1, NRXN3, MSRA, and TFAP2B (PMID:21674055)
• The MSRA gene located on chromosome 8 was found to be associated with the phenotype of schizophrenia in Chinese first-episode schizophrenia patients. (PMID:21679298)
• The haplotype with the lowest P value showed association with Meconium ileus in an independent sample of 1,335 unrelated cystic fibrosis patients (PMID:22438829)
• Data show that glutaredoxin acts as a reductant for methionine sulfoxide reductases A and B (MsrA and MsrB) with or without resolving cysteine. (PMID:22634633)
• The MSRA rs10903323 gene polymorphism may be implicated in the increased risk to develop cardiovascular events, in particular ischaemic heart disease, observed in rheumatoid arthritis patients. (PMID:22657383)
• Mammalian and yeast MSRA reduced free methionine sulfoxide much more efficiently than MSRB. (PMID:22867795)
• The MSRA rs10903323 G/A variant allele is associated with Rheumatoid Arthritis development, especially among male patients, older patients, C-Reactive Protein-positive patients, and anti-cyclic citrullinated peptide negative patients. (PMID:23244167)
• We hypothesize that the activity of MsrA can be employed as a marker for the isolation of stem and progenitor cell subpopulations for cell therapy applications. (PMID:23415806)
• The functional MSRA rs10903323 G/A polymorphism is associated with coronary artery disease development. (PMID:23880405)
• Silencing the expression of the main Msr elements-MsrA, MsrB1, or MsrB2 exacerbates sensitivity toward oxidative stress. (PMID:23988788)
• ARD1 has a crucial role in the cellular response to oxidative stress as a bona fide regulator of MSRA. (PMID:25341044)
• The association of MsrA haplotypes with executive functions indicated that MsrA is associated with executive function defects in bipolar I disorder patients. (PMID:26117066)
• this study we have identified, for the first time, compounds structurally related to the natural products fusaricidins that markedly activate recombinant bovine and human MsrA and human MsrB. (PMID:26718410)
• Data show that miR-193b, by directly targeting focal adhesion kinase (FAK), CRK-like proto-oncogene (CRKL), and methionine sulfoxide reductase A (MSRA), regulates focal adhesion signaling and ROS signaling, which play pivotal roles in liposarcomagenesis and adipogenic differentiation. (PMID:28882999)
• myristoylated MSRA is a late endosomal protein that may play a role in lipid metabolism or may protect endosomal proteins from oxidative damage. (PMID:29593096)
• Three SNPs (RUNX3 rs7553295 G > T, AMD1 rs1279590 G > A and MSRA rs73534533 C > A) were replicated in the validation dataset, and their meta-analysis showed an adjusted hazards ratio [HR] of 0.82 [95% confidence interval (CI) =0.75-0.89] and pmeta = 2.86 x 10(-6) , 0.81 (0.73-0.91) and pmeta = 4.63 x 10(-4) , and 0.77 (0.68-0.89) and pmeta = 2.07 x 10(-4) , respectively). (PMID:30650190)
• Methionine sulfoxide reductase A (MsrA) modulates cells and protects against Mycoplasma genitalium induced cytotoxicity. (PMID:32222467)
• Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients. (PMID:34674978)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Msra	ENSMUSG00000054733
rattus_norvegicus	Msra	ENSRNOG00000012440
drosophila_melanogaster	MsrA	FBGN0000565
caenorhabditis_elegans		WBGENE00018393

Paralogs (3): MSRB2 (ENSG00000148450), MSRB3 (ENSG00000174099), MSRB1 (ENSG00000198736)

Protein

Protein identifiers

Mitochondrial peptide methionine sulfoxide reductase — Q9UJ68 (reviewed: Q9UJ68)

Alternative names: Peptide-methionine (S)-S-oxide reductase, Protein-methionine-S-oxide reductase

All UniProt accessions (5): Q9UJ68, E5RIA9, E5RJK1, E9PJ70, H0YAN3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine. Has an important function as a repair enzyme for proteins that have been inactivated by oxidation. Plays a crucial role in repairing oxidized methionine residues in key lens proteins, such as alpha-crystallin (CRYAA/CRYAB) and cytochrome c (CYCS), thereby restoring their function and maintaining lens transparency.

Subcellular location. Mitochondrion. Mitochondrion matrix. Cytoplasm Cytoplasm Cytoplasm. Nucleus Cytoplasm. Membrane.

Tissue specificity. Ubiquitous. Highest expression in adult kidney and cerebellum, followed by liver, heart ventricles, bone marrow and hippocampus.

Miscellaneous. Produced by alternative splicing. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative splicing. Produced by alternative initiation.

Similarity. Belongs to the MsrA Met sulfoxide reductase family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9UJ68-1	1, MsrA1, mitoMSRA, a	yes
Q9UJ68-2	2, MsrA2, d
Q9UJ68-3	3, MsrA3, cytoMSRA, c
Q9UJ68-4	4, b
Q9UJ68-5	5

RefSeq proteins (4): NP_001129142, NP_001129143, NP_001186658, NP_036463* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002569	Met_Sox_Rdtase_MsrA_dom	Domain
IPR036509	Met_Sox_Rdtase_MsrA_sf	Homologous_superfamily
IPR050162	MsrA_MetSO_reductase	Family

Pfam: PF01625

Enzyme classification (BRENDA):

• EC 1.8.4.11 — peptide-methionine (S)-S-oxide reductase (BRENDA: 97 organisms, 269 substrates, 11 inhibitors, 63 Km, 54 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
THIOREDOXIN	0.0018–0.19	15
DABSYL-L-METHIONINE (S)-S-OXIDE	0.14–1.03	7
DABSYL-L-METHIONINE (S)-SULFOXIDE	0.04–0.17	6
L-METHIONINE (S)-SULFOXIDE	0.044–19	6
L-METHIONINE-(S)-S-OXIDE	0.135–0.55	4
N-ACETYL-L-METHIONINE-(S)-S-OXIDE	0.0249–1.4	4
TRYPAREDOXIN I	0.013–0.033	3
9-FLUORENYLMETHYL CHLOROFORMATE-LABELED L-METHIO	1.1–2.12	2
DABSYL-L-METHIONINE-(S)-S-OXIDE	0.34–4.3	2
DABSYLATED L-METHIONINE (S)-SULFOXIDE	4–10.2	2
DITHIOTHREITOL	0.84–15	2
GLUTAREDOXIN 2	0.25–0.27	2
CALMODULIN	0.197	1
DABSYL L-METHIONINE-(S)-SULFOXIDE	1.18	1
L-METHIONINE (R,S)-SULFOXIDE	9	1

Catalyzed reactions (Rhea), 2 shown:

• L-methionyl-[protein] + [thioredoxin]-disulfide + H2O = L-methionyl-(S)-S-oxide-[protein] + [thioredoxin]-dithiol (RHEA:14217)
• [thioredoxin]-disulfide + L-methionine + H2O = L-methionine (S)-S-oxide + [thioredoxin]-dithiol (RHEA:19993)

UniProt features (18 total): splice variant 4, mutagenesis site 4, sequence conflict 2, modified residue 2, disulfide bond 2, transit peptide 1, chain 1, lipid moiety-binding region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJ68-F1	89.13	0.81

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): 74 (cysteine sulfenic acid (-soh) intermediate)

Post-translational modifications (3): 2, 106, 106

Disulfide bonds (2): 74–220, 220–229

Mutagenesis-validated functional residues (4):

Position	Phenotype
6	impaired subcellular location.
7	impaired subcellular location.
11–13	impaired subcellular location.
22	impaired subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5676934	Protein repair
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 155 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, RACCACAR_AML_Q6, MARTINEZ_RB1_TARGETS_UP, GOBP_METHIONINE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, MCCABE_HOXC6_TARGETS_CANCER_UP, GOBP_SULFUR_AMINO_ACID_METABOLIC_PROCESS, GRADE_COLON_AND_RECTAL_CANCER_DN, MARTINEZ_RB1_AND_TP53_TARGETS_UP, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_MITOCHONDRIAL_MATRIX, GAVIN_FOXP3_TARGETS_CLUSTER_P7, OSF2_Q6

GO Biological Process (5): L-methionine metabolic process (GO:0006555), response to oxidative stress (GO:0006979), protein repair (GO:0030091), cellular response to oxidative stress (GO:0034599), protein modification process (GO:0036211)

GO Molecular Function (5): peptide-methionine (S)-S-oxide reductase activity (GO:0008113), L-methionine (S)-S-oxide reductase activity (GO:0033744), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), obsolete L-methionine-(S)-S-oxide reductase activity (GO:0036456)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), membrane (GO:0016020), nuclear body (GO:0016604), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein metabolic process	2
oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor	2
intracellular membrane-bounded organelle	2
cytoplasm	2
sulfur amino acid metabolic process	1
L-amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
response to stress	1
response to oxidative stress	1
cellular response to chemical stress	1
macromolecule modification	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
mitochondrion	1
intracellular organelle lumen	1
nucleoplasm	1
intracellular membraneless organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

2295 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MSRA	RP1L1	Q8IWN7	943
MSRA	MSRB2	Q9Y3D2	916
MSRA	SOX7	Q9BT81	860
MSRA	MSRB3	Q8IXL7	742
MSRA	GLRX	P35754	734
MSRA	MSRB1	Q9NZV6	699
MSRA	APEH	P13798	697
MSRA	TXN	P10599	634
MSRA	LYPLAL1	Q5VWZ2	537
MSRA	SELENOT	P62341	530
MSRA	SELENOO	Q9BVL4	525
MSRA	TMEM18	Q96B42	520
MSRA	ATP6V1B1	P15313	512
MSRA	H7C2H4	H7C2H4	489
MSRA	P0DN79	P0DN79	489

IntAct

28 interactions, top by confidence:

A	B	Type	Score
SELENBP1	MSRA	psi-mi:“MI:0915”(physical association)	0.560
CTNNA3	MSRA	psi-mi:“MI:0915”(physical association)	0.560
EFCAB11	MSRA	psi-mi:“MI:0915”(physical association)	0.560
MSRA	FBXL3	psi-mi:“MI:0915”(physical association)	0.560
P4HA3	MSRA	psi-mi:“MI:0915”(physical association)	0.560
MSRA	HPCAL4	psi-mi:“MI:0915”(physical association)	0.560
BMAL2	CLOCK	psi-mi:“MI:0914”(association)	0.550
MSRA	UBASH3B	psi-mi:“MI:0915”(physical association)	0.500
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
IRF3	USP19	psi-mi:“MI:0914”(association)	0.350
DRD2	SNX4	psi-mi:“MI:0914”(association)	0.350
KCNMB2	TK1	psi-mi:“MI:0914”(association)	0.350
MSRA	TRIM26	psi-mi:“MI:0914”(association)	0.350
SLC30A10	GOLIM4	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
CTNNA3	MSRA	psi-mi:“MI:0915”(physical association)	0.000
EFCAB11	MSRA	psi-mi:“MI:0915”(physical association)	0.000
FBXL3	MSRA	psi-mi:“MI:0915”(physical association)	0.000
HPCAL4	MSRA	psi-mi:“MI:0915”(physical association)	0.000
SELENBP1	MSRA	psi-mi:“MI:0915”(physical association)	0.000
P4HA3	MSRA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): HSPE1 (Co-fractionation), MSRA (Affinity Capture-MS), MSRA (Affinity Capture-MS), MSRA (Affinity Capture-MS), MSRA (Affinity Capture-RNA), MSRA (Two-hybrid), MSRA (Two-hybrid), MSRA (Two-hybrid), MSRA (Two-hybrid), MSRA (Two-hybrid), CTNNA3 (Two-hybrid), MSRA (Proximity Label-MS), MSRA (Proximity Label-MS), MSRA (Proximity Label-MS), MSRA (Affinity Capture-MS)

ESM2 similar proteins: A4QHY3, A4TRL2, A5VVX1, A6WYH5, A7FMV2, A8G8X6, A8IPQ8, A8M3K6, A9MCZ5, A9R574, A9WW77, B0KJ25, B1JE82, B1JML1, B2K2M6, B2SC53, B6IS04, B7K079, B7V3B1, C0RMK6, P54149, P54153, P72622, Q02EZ9, Q1CBX8, Q1I3L0, Q21JK7, Q2W5W8, Q2YJM1, Q48CJ2, Q4ZM24, Q576P8, Q66F89, Q6NEL2, Q7D255, Q88AI5, Q88QZ8, Q8FLU6, Q8FUZ0, Q8NLL5

Diamond homologs: A3CUG3, A3M1W6, A4FYX5, A4TRL2, A4X3E5, A5VVX1, A6VFD6, A6WYH5, A7FMV2, A7MM56, A7ZV98, A8A7X5, A8G8X6, A8M3K6, A9AB97, A9MCZ5, A9R574, A9WW77, B0V4P7, B0VL72, B1ISY2, B1JML1, B1LRA3, B1XDW8, B2I399, B2K2M6, B2SC53, B2TZL3, B5Z3H5, B6I2D2, B6IS04, B7H0P7, B7I4T7, B7K079, B7LCT1, B7M9I1, B7MLN1, B7MTA1, B7NGF6, B7NUD2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	74
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
563505	GRCh37/hg19 8p23.1(chr8:9952770-10603276)x3	Likely pathogenic

SpliceAI

4704 predictions. Top by Δscore:

Variant	Effect	Δscore
8:10054655:GCGG:G	donor_gain	1.0000
8:10054657:GG:G	donor_gain	1.0000
8:10054658:GG:G	donor_gain	1.0000
8:10054659:G:GG	donor_gain	1.0000
8:10054660:T:A	donor_loss	1.0000
8:10245219:CTCAG:C	donor_loss	1.0000
8:10245220:TCAG:T	donor_loss	1.0000
8:10245221:CAGG:C	donor_loss	1.0000
8:10245222:AG:A	donor_loss	1.0000
8:10245223:GGTA:G	donor_loss	1.0000
8:10245225:T:G	donor_loss	1.0000
8:10301531:A:AG	acceptor_gain	1.0000
8:10301532:A:G	acceptor_gain	1.0000
8:10301651:G:GG	donor_gain	1.0000
8:10319882:GGT:G	acceptor_gain	1.0000
8:10319990:G:GA	donor_loss	1.0000
8:10319990:G:GG	donor_gain	1.0000
8:10319991:T:A	donor_loss	1.0000
8:10353675:A:G	donor_gain	1.0000
8:10379539:G:GT	donor_gain	1.0000
8:10411267:G:GT	donor_gain	1.0000
8:10411268:A:T	donor_gain	1.0000
8:10428146:A:AC	acceptor_loss	1.0000
8:10428147:G:GT	acceptor_loss	1.0000
8:10054745:G:GT	donor_gain	0.9900
8:10155632:G:GT	donor_gain	0.9900
8:10207831:A:AG	acceptor_gain	0.9900
8:10207832:G:GG	acceptor_gain	0.9900
8:10245101:AAG:A	acceptor_gain	0.9900
8:10245102:A:G	acceptor_gain	0.9900

AlphaMissense

1531 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:10301611:T:C	F137L	0.987
8:10301613:C:A	F137L	0.987
8:10301613:C:G	F137L	0.987
8:10301614:T:A	W138R	0.986
8:10301614:T:C	W138R	0.986
8:10301561:G:C	R120P	0.985
8:10245115:T:C	F75L	0.984
8:10245117:C:A	F75L	0.984
8:10245117:C:G	F75L	0.984
8:10245175:T:C	F95L	0.983
8:10245177:T:A	F95L	0.983
8:10245177:T:G	F95L	0.983
8:10301616:G:C	W138C	0.982
8:10301616:G:T	W138C	0.982
8:10207871:T:C	F61L	0.980
8:10207873:C:A	F61L	0.980
8:10207873:C:G	F61L	0.980
8:10428205:T:C	F201L	0.980
8:10428207:C:A	F201L	0.980
8:10428207:C:G	F201L	0.980
8:10245129:A:C	E79D	0.977
8:10245129:A:T	E79D	0.977
8:10245120:G:C	W76C	0.973
8:10245120:G:T	W76C	0.973
8:10319919:G:C	R158P	0.973
8:10428234:G:C	Q210H	0.973
8:10428234:G:T	Q210H	0.973
8:10428231:G:C	Q209H	0.972
8:10428231:G:T	Q209H	0.972
8:10245128:A:T	E79V	0.971

dbSNP variants (sampled 300 via entrez): RS1000012237 (8:10406047 C>G), RS1000013843 (8:10210656 A>C,T), RS1000014945 (8:10329484 C>T), RS1000020221 (8:10281505 C>G,T), RS1000026644 (8:10142729 T>C), RS1000031908 (8:10378709 C>G), RS1000035550 (8:10324112 C>T), RS1000035663 (8:10227480 G>A), RS1000037558 (8:10338512 A>G), RS1000048294 (8:10350857 C>A,T), RS1000061214 (8:10132170 G>C), RS1000065109 (8:10118373 A>G), RS1000066692 (8:10197014 T>C), RS1000068069 (8:10233679 A>G), RS1000070928 (8:10131969 A>C,G,T)

Disease associations

OMIM: gene MIM:601250 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

195 associations (top):

Study	Trait	p-value
GCST000398_1	Hypertension	4.000000e-06
GCST000428_2	Adiposity	9.000000e-09
GCST000663_5	Obesity (early onset extreme)	2.000000e-08
GCST000676_2	Alzheimer’s disease	3.000000e-06
GCST001110_1	Schizophrenia	4.000000e-06
GCST001567_7	Bipolar disorder and schizophrenia	3.000000e-06
GCST001712_37	Myopia (pathological)	6.000000e-07
GCST001958_18	Bulimia nervosa	8.000000e-06
GCST002566_10	Response to chemotherapy in breast cancer hypertensive cases (cumulative dose) (bevacizumab)	2.000000e-06
GCST003048_59	Schizophrenia	4.000000e-08
GCST003428_1	Chronotype	2.000000e-09
GCST003738_2	Barrett’s esophagus	2.000000e-09
GCST003740_4	Barrett’s esophagus or Esophageal adenocarcinoma	5.000000e-10
GCST003998_21	Joint mobility (Beighton score)	4.000000e-07
GCST003999_24	Nose size	4.000000e-07
GCST004600_39	Eosinophil percentage of white cells	3.000000e-09
GCST004617_15	Eosinophil percentage of granulocytes	2.000000e-09
GCST004946_26	Schizophrenia	3.000000e-08
GCST005173_21	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	8.000000e-06
GCST005175_61	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	2.000000e-06
GCST005343_2	Plasma kynurenine to tryptophan ratio in major depressive disorder	6.000000e-08
GCST005752_37	Systemic lupus erythematosus	8.000000e-06
GCST005835_2	Remission after SSRI treatment in MDD or neuroticism	9.000000e-09
GCST006166_104	Diastolic blood pressure x alcohol consumption interaction (2df test)	6.000000e-17
GCST006166_68	Diastolic blood pressure x alcohol consumption interaction (2df test)	5.000000e-15
GCST006166_69	Diastolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-15
GCST006168_51	Pulse pressure x alcohol consumption interaction (2df test)	6.000000e-23
GCST006170_17	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	6.000000e-13
GCST006170_29	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	3.000000e-10
GCST006172_12	Mean arterial pressure x alcohol consumption (light vs heavy) interaction (2df test)	2.000000e-09

EFO canonical traits (44, from GWAS)

EFO ID	Trait name
EFO:0004207	pathological myopia
EFO:0005944	cumulative dose response to bevacizumab
EFO:0007905	joint hypermobility measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0004723	coronary artery calcification
EFO:0008530	kynurenine:tryptophan ratio
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007660	neuroticism measurement
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0006527	smoking status measurement
EFO:0009594	irritability measurement
EFO:0009589	worry measurement
EFO:0004340	body mass index
EFO:0004338	body weight
EFO:0008579	risk-taking behaviour
EFO:0009749	age at first sexual intercourse measurement
EFO:0007876	insomnia measurement
EFO:0009759	Chronic Obstructive Asthma
EFO:0009928	Diuretic use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009933	Thyroid preparation use measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0005670	smoking initiation
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	8
Aflatoxin B1	affects expression, decreases expression, decreases methylation	4
Cisplatin	affects expression, affects cotreatment, decreases expression	3
sodium arsenite	increases expression	2
Aerosols	affects expression, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
tert-Butylhydroperoxide	decreases expression, decreases reaction, decreases response to substance	2
aristolochic acid I	decreases expression, increases expression	1
urushiol	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases methylation, decreases methylation, affects cotreatment	1
S-methylcysteine	decreases response to substance, increases reaction	1
arsenite	increases reaction, affects binding	1
sodium bichromate	decreases expression	1
chloramine-T	decreases response to substance, increases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	affects methylation	1
cerous chloride	decreases expression	1
aflatoxin B2	decreases methylation	1
cadmium sulfide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
salvianolic acid B	decreases expression, decreases reaction	1
K 7174	decreases expression	1
2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole	decreases expression	1
bisphenol B	increases expression	1

Clinical trials (associated diseases)

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