MRI1

protein-coding

methylthioribose-1-phosphate isomerase 1

Gene summary

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). [provided by RefSeq, Jul 2016]

MANE transcript

NM_001031727.4

Inheritance

—

ClinVar variants

U:87B:10

Top phenotype

Severe cystic degeneration of the brain

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr19:13,764,522-13,774,282

External References & Databases

Ensembl (ENSG00000037757)

Transcript & Mutation Effects

hg38 • Region Span ~9.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MRI1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 77

not providedTotal: 18

Severe cystic degeneration of the brainTotal: 1

Infantile epilepsyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001031727.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	4 clinvar	1 clinvar	7
missense			78 clinvar	3 clinvar	2 clinvar	83
nonsense			2 clinvar			2
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	87	7	3	97

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001031727.4	RefSeq	NP_001026897.1	6	MANE Select
ENST00000040663.8	Ensembl	ENSP00000040663.5	6	MANE Select
NM_001329572.2	RefSeq	NP_001316501.1	6	Standard
NM_032285.4	RefSeq	NP_115661.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cysteine and methionine metabolism - Homo sapiens (human)
Methionine De Novo and Salvage Pathway
Metabolism of polyamines
Metabolism of amino acids and derivatives
Methionine salvage pathway

Biological Process

L-methionine salvage from S-adenosylmethionine
L-methionine salvage from methylthioadenosine

Molecular Function

identical protein binding
S-methyl-5-thioribose-1-phosphate isomerase activity

Cellular Component

fibrillar center
nucleoplasm
cytosol
cell projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000040663
Coding exons: 6
Length: 9751
Individuals with no LoFs: 125692
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125743
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.348	203	217	0.934	0.0000127	2292
Missense (PolyPhen)		98	94.103	1.0414		980
Synonymous	0.367	93	97.6	0.953	0.00000577	847
Loss of Function	1.32	7	11.9	0.587	6.77e-7	139

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00064	0.00064	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00021	0.00020	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000255|HAMAP-Rule:MF_03119, ECO:0000269|PubMed:19620624}.;

Intolerance Scores

LoFtool: 0.194
RVIS EVS: 0.51
RVIS percentile EVS: 80.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0654

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium