MRI1

Summary

MRI1 (methylthioribose-1-phosphate isomerase 1, HGNC:28469) is a protein-coding gene on chromosome 19p13.13, encoding Methylthioribose-1-phosphate isomerase (Q9BV20). Catalyzes the interconversion of methylthioribose-1-phosphate (MTR-1-P) into methylthioribulose-1-phosphate (MTRu-1-P).

This enzyme functions in the methionine salvage pathway by catalyzing the interconversion of methylthioribose-1-phosphate and methythioribulose-1-phosphate. Elevated expression of the encoded protein is associated with metastatic melanoma and this protein promotes melanoma cell invasion independent of its enzymatic activity. Mutations in this gene may be associated with vanishing white matter disease (VMWD).

Source: NCBI Gene 84245 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 118 total
• MANE Select transcript: NM_001031727

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28469
Approved symbol	MRI1
Name	methylthioribose-1-phosphate isomerase 1
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC3207, Ypr118w, mtnA, MRDI
Ensembl gene	ENSG00000037757
Ensembl biotype	protein_coding
OMIM	615105
Entrez	84245

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 retained_intron

ENST00000040663, ENST00000319545, ENST00000588526, ENST00000589290, ENST00000591688, ENST00000593245, ENST00000866694, ENST00000912602, ENST00000953596

RefSeq mRNA: 3 — MANE Select: NM_001031727 NM_001031727, NM_001329572, NM_032285

CCDS: CCDS12297, CCDS32923

Canonical transcript exons

ENST00000040663 — 6 exons

Exon	Start	End
ENSE00000836495	13768561	13768737
ENSE00000836496	13768824	13769048
ENSE00001415106	13772121	13774282
ENSE00003504415	13764871	13765109
ENSE00003525261	13764522	13764720
ENSE00003592798	13765954	13766129

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 96.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7347 / max 195.1644, expressed in 1796 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174157	25.7347	1796

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.20	silver quality
right uterine tube	UBERON:0001302	91.17	gold quality
endocervix	UBERON:0000458	90.25	gold quality
metanephros cortex	UBERON:0010533	90.12	gold quality
sural nerve	UBERON:0015488	89.12	gold quality
body of uterus	UBERON:0009853	88.61	gold quality
ectocervix	UBERON:0012249	88.34	gold quality
right ovary	UBERON:0002118	88.29	gold quality
left ovary	UBERON:0002119	88.29	gold quality
skin of abdomen	UBERON:0001416	88.12	gold quality
right adrenal gland cortex	UBERON:0035827	87.97	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.84	gold quality
left lobe of thyroid gland	UBERON:0001120	87.75	gold quality
descending thoracic aorta	UBERON:0002345	87.74	gold quality
right adrenal gland	UBERON:0001233	87.66	gold quality
minor salivary gland	UBERON:0001830	87.63	gold quality
right lobe of thyroid gland	UBERON:0001119	87.62	gold quality
granulocyte	CL:0000094	87.59	gold quality
skin of leg	UBERON:0001511	87.58	gold quality
left uterine tube	UBERON:0001303	87.40	gold quality
left coronary artery	UBERON:0001626	87.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.37	gold quality
thoracic aorta	UBERON:0001515	87.14	gold quality
body of stomach	UBERON:0001161	87.10	gold quality
ascending aorta	UBERON:0001496	87.06	gold quality
tibial nerve	UBERON:0001323	87.02	gold quality
right lung	UBERON:0002167	87.01	gold quality
left adrenal gland	UBERON:0001234	86.99	gold quality
left adrenal gland cortex	UBERON:0035825	86.94	gold quality
spleen	UBERON:0002106	86.73	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting MRI1, 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-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
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-4731-5P	99.89	67.23	2537
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351

Literature-anchored findings (GeneRIF, showing 3)

• Identification of MRI1, encoding translation initiation factor eIF-2B subunit alpha/beta/delta-like protein, as a candidate locus for infantile epilepsy with severe cystic degeneration of the brain. (PMID:23124037)
• Data indicate that the structural elements in MRDI distal from the MTR-1-P catalytic site are responsible for the invasion phenotype. (PMID:23859498)
• Elevated expression of EI2BL promoted non-small cell lung cancer cell proliferation, migration and invasion. (PMID:31586937)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mri1	ENSDARG00000075754
mus_musculus	Mri1	ENSMUSG00000004996
rattus_norvegicus	Mri1	ENSRNOG00000026211
drosophila_melanogaster	CG11334	FBGN0039849
caenorhabditis_elegans		WBGENE00007236

Paralogs (3): EIF2B1 (ENSG00000111361), EIF2B4 (ENSG00000115211), EIF2B2 (ENSG00000119718)

Protein

Protein identifiers

Methylthioribose-1-phosphate isomerase — Q9BV20 (reviewed: Q9BV20)

Alternative names: Mediator of RhoA-dependent invasion, S-methyl-5-thioribose-1-phosphate isomerase, Translation initiation factor eIF-2B subunit alpha/beta/delta-like protein

All UniProt accessions (1): Q9BV20

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the interconversion of methylthioribose-1-phosphate (MTR-1-P) into methylthioribulose-1-phosphate (MTRu-1-P). Independently from catalytic activity, promotes cell invasion in response to constitutive RhoA activation by promoting FAK tyrosine phosphorylation and stress fiber turnover.

Subcellular location. Nucleus. Cytoplasm. Cell projection.

Induction. By RhoA activation in cancer cells (at protein level).

Pathway. Amino-acid biosynthesis; L-methionine biosynthesis via salvage pathway; L-methionine from S-methyl-5-thio-alpha-D-ribose 1-phosphate: step 1/6.

Similarity. Belongs to the eIF-2B alpha/beta/delta subunits family. MtnA subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BV20-1	1	yes
Q9BV20-2	2

RefSeq proteins (3): NP_001026897, NP_001316501, NP_115661 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000649	IF-2B-related	Family
IPR005251	IF-M1Pi	Family
IPR011559	Initiation_fac_2B_a/b/d	Family
IPR027363	M1Pi_N	Homologous_superfamily
IPR037171	NagB/RpiA_transferase-like	Homologous_superfamily
IPR042529	IF_2B-like_C	Homologous_superfamily

Pfam: PF01008

Enzyme classification (BRENDA):

• EC 5.3.1.23 — S-methyl-5-thioribose-1-phosphate isomerase (BRENDA: 7 organisms, 11 substrates, 1 inhibitors, 5 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5-DEOXY-D-RIBOSE	1.6	1
5-DEOXY-D-RIBOSE 1-PHOSPHATE	0.41	1
S-METHYL-5-THIO-ALPHA-D-RIBOSE 1-PHOSPHATE	0.138	1

Catalyzed reactions (Rhea), 1 shown:

• 5-(methylsulfanyl)-alpha-D-ribose 1-phosphate = 5-(methylsulfanyl)-D-ribulose 1-phosphate (RHEA:19989)

UniProt features (46 total): helix 18, strand 15, turn 4, sequence variant 2, mutagenesis site 2, chain 1, active site 1, site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4LDR	X-RAY DIFFRACTION	2.29
4LDQ	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV20-F1	94.89	0.94

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 (2): 248 (proton donor); 168 (transition state stabilizer)

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (2):

Position	Phenotype
168	abolishes enzymatic activity.
248	abolishes enzymatic activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1237112	Methionine salvage pathway
R-HSA-1430728	Metabolism
R-HSA-1614635	Sulfur amino acid metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 126 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, TGCGCANK_UNKNOWN, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ASPARTATE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, TGCTGAY_UNKNOWN, HFH8_01, GOBP_METHIONINE_BIOSYNTHETIC_PROCESS, GOBP_METHIONINE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, SANSOM_APC_TARGETS_UP, GCM_NF2

GO Biological Process (3): obsolete L-methionine salvage from methylthioadenosine (GO:0019509), amino acid biosynthetic process (GO:0008652), obsolete methionine biosynthetic process (GO:0009086)

GO Molecular Function (4): identical protein binding (GO:0042802), S-methyl-5-thioribose-1-phosphate isomerase activity (GO:0046523), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), cytosol (GO:0005829), cell projection (GO:0042995), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Sulfur amino acid metabolism	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
amino acid metabolic process	1
biosynthetic process	1
protein binding	1
intramolecular oxidoreductase activity, interconverting aldoses and ketoses	1
binding	1
catalytic activity	1
nucleolus	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRI1	CYREN	Q9BWK5	890
MRI1	ENOPH1	Q9UHY7	808
MRI1	ADI1	Q9BV57	775
MRI1	APIP	Q96GX9	673
MRI1	MTAP	Q13126	541
MRI1	FAM181A	Q8N9Y4	540
MRI1	BHMT2	Q9H2M3	507
MRI1	NTN3	O00634	456
MRI1	TMEM9	Q9P0T7	449
MRI1	RNF26	Q9BY78	437
MRI1	SLC9D1	Q6UWJ1	430
MRI1	SRM	P19623	421
MRI1	CRB2	Q5IJ48	417
MRI1	MTR	Q99707	410
MRI1	COL18A1	P39060	406

IntAct

57 interactions, top by confidence:

A	B	Type	Score
CUL9	TP53	psi-mi:“MI:0914”(association)	0.920
MRI1	MRI1	psi-mi:“MI:0915”(physical association)	0.820
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
MRI1	PICK1	psi-mi:“MI:0915”(physical association)	0.560
MRI1	COG6	psi-mi:“MI:0915”(physical association)	0.560
MRI1	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
CASP6	MRI1	psi-mi:“MI:0915”(physical association)	0.560
MRI1	LAMP2	psi-mi:“MI:0915”(physical association)	0.560
MRI1	BAG6	psi-mi:“MI:0915”(physical association)	0.560
MRI1	NUP58	psi-mi:“MI:0915”(physical association)	0.560
MRI1	F11R	psi-mi:“MI:0915”(physical association)	0.560
MRI1	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	MRI1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (55): MRI1 (Two-hybrid), MRI1 (Two-hybrid), ADI1 (Co-fractionation), MRI1 (Affinity Capture-Western), MRI1 (Affinity Capture-MS), MRI1 (Affinity Capture-MS), MRI1 (Affinity Capture-RNA), MRI1 (Affinity Capture-MS), MRI1 (Affinity Capture-MS), MRI1 (Two-hybrid), PICK1 (Two-hybrid), COG6 (Two-hybrid), PLEKHF2 (Two-hybrid), MRI1 (Affinity Capture-MS), MRI1 (Affinity Capture-MS)

ESM2 similar proteins: A0PU14, A0RW81, A0RX34, A0RXF8, A1R5S0, A1U6H0, A4T2J5, A4YRL1, A9JRE2, B0B939, B0BAR8, B2HMG0, B2UNF6, B3DPS5, B4SE13, B8DVU2, O26230, O27181, O27698, O84817, P16245, P26925, P35660, Q0B006, Q0C1A1, Q0VMX5, Q16A32, Q1GUW8, Q1QX56, Q2FKX5, Q2NA97, Q30VM1, Q39YF3, Q3B121, Q3B2C2, Q3B2H3, Q3B5E3, Q3KKN0, Q4JWC7, Q5FNM7

Diamond homologs: A1CGN9, A1CY38, A2ZCP0, A3LN21, A4HQ10, A4ICE5, A4S068, A5D1G8, A5DNT0, A6R364, A6RHT9, A6ZWZ9, A7EGZ3, A7RF00, A7TSA5, A9JRE2, A9UQ62, B0D0U4, B0Y5C3, B2AML6, B2VZQ8, B3LK82, B3M098, B3P538, B3RLE6, B4GYU1, B4I029, B4JRX2, B4K8A4, B4LWZ8, B4NG41, B4PNE2, B4QSM8, B5VTQ8, B6H5R4, B6K4Q2, B6QRG1, B6TZD1, B8C6V3, B8M7D2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	12
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1081 predictions. Top by Δscore:

Variant	Effect	Δscore
19:13764718:A:T	donor_gain	1.0000
19:13764718:AAG:A	donor_loss	1.0000
19:13764719:AG:A	donor_loss	1.0000
19:13764720:GG:G	donor_loss	1.0000
19:13765146:G:GT	donor_gain	1.0000
19:13765952:A:AG	acceptor_gain	1.0000
19:13765952:AGAGT:A	acceptor_gain	1.0000
19:13765953:G:GA	acceptor_gain	1.0000
19:13765953:GA:G	acceptor_gain	1.0000
19:13765953:GAGTG:G	acceptor_gain	1.0000
19:13768528:G:A	acceptor_gain	1.0000
19:13768736:AG:A	donor_loss	1.0000
19:13768737:GGTAA:G	donor_loss	1.0000
19:13768738:GTAAG:G	donor_loss	1.0000
19:13768739:T:G	donor_loss	1.0000
19:13768810:C:CA	acceptor_gain	1.0000
19:13768821:CAGC:C	acceptor_loss	1.0000
19:13768822:A:AG	acceptor_gain	1.0000
19:13768822:AGCT:A	acceptor_gain	1.0000
19:13768823:G:GT	acceptor_gain	1.0000
19:13768823:GC:G	acceptor_gain	1.0000
19:13768823:GCT:G	acceptor_gain	1.0000
19:13768823:GCTG:G	acceptor_gain	1.0000
19:13768823:GCTGT:G	acceptor_gain	1.0000
19:13769045:CCTG:C	donor_gain	1.0000
19:13769047:TGGTA:T	donor_loss	1.0000
19:13769049:G:C	donor_loss	1.0000
19:13769049:G:GG	donor_gain	1.0000
19:13764694:GCC:G	donor_gain	0.9900
19:13764717:G:GT	donor_gain	0.9900

AlphaMissense

2339 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:13768876:G:C	K259N	0.997
19:13768876:G:T	K259N	0.997
19:13772144:T:C	F325L	0.997
19:13772146:C:A	F325L	0.997
19:13772146:C:G	F325L	0.997
19:13766089:C:A	N169K	0.996
19:13766089:C:G	N169K	0.996
19:13764910:A:C	S58R	0.995
19:13764912:C:A	S58R	0.995
19:13764912:C:G	S58R	0.995
19:13766086:T:G	C168W	0.995
19:13768842:A:T	D248V	0.995
19:13768873:C:A	N258K	0.995
19:13768873:C:G	N258K	0.995
19:13768843:C:A	D248E	0.994
19:13768843:C:G	D248E	0.994
19:13768845:G:C	R249P	0.994
19:13766085:G:A	C168Y	0.993
19:13768841:G:C	D248H	0.993
19:13768842:A:C	D248A	0.993
19:13768874:A:C	K259Q	0.990
19:13768874:A:G	K259E	0.990
19:13766084:T:C	C168R	0.989
19:13768842:A:G	D248G	0.989
19:13768869:C:A	A257D	0.989
19:13768935:C:A	A279D	0.989
19:13772137:T:A	N322K	0.988
19:13772137:T:G	N322K	0.988
19:13768696:A:T	D228V	0.987
19:13768896:C:A	A266D	0.987

dbSNP variants (sampled 300 via entrez): RS1000063474 (19:13764464 C>T), RS1000111408 (19:13769648 G>A), RS1000226332 (19:13769453 A>G), RS1000447039 (19:13767224 T>C), RS1000498029 (19:13766851 G>A), RS1000662604 (19:13771690 C>A,T), RS1000771175 (19:13774561 C>T), RS1001007266 (19:13771964 A>G), RS1001139616 (19:13765359 G>A), RS1001508787 (19:13765602 C>T), RS1001524795 (19:13764952 C>T), RS1001673217 (19:13769962 A>G), RS1002279377 (19:13771134 G>A), RS1002648121 (19:13774277 T>C), RS1003082906 (19:13771215 AC>A)

Disease associations

OMIM: gene MIM:615105 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_143	Brain morphology (MOSTest)	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	5
bisphenol A	decreases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Valproic Acid	affects expression, increases methylation	2
bismuth tripotassium dicitrate	increases expression	1
2,4,6-tribromophenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Arsenic	increases abundance, increases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Isoniazid	decreases expression	1
Ivermectin	decreases expression	1
Quercetin	increases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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