MPI

mannose phosphate isomerase

Basic information

Region (hg38): 15:74890005-74902219

Links

ENSG00000178802 ∙ NCBI:4351 ∙ OMIM:154550 ∙ HGNC:7216 ∙ Uniprot:P34949 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MPI-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• MPI-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• MPI-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• MPI-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• MPI-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• MPI-congenital disorder of glycosylation (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Ib	AR	Biochemical; Hematologic	Treatment with oral mannose can result in clinical improvement; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Gastrointestinal; Hematologic	9585601; 9525984; 10484808; 10980531; 11134235; 12414827; 18285818; 19065443; 19101627; 20301507; 20679665
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MPI gene.

• MPI-congenital_disorder_of_glycosylation (512 variants)
• not_provided (43 variants)
• Inborn_genetic_diseases (31 variants)
• not_specified (29 variants)
• MPI-related_disorder (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MPI gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002435.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	183	1	191
missense	2	19	101	8		130
nonsense	6	14	1			21
start loss		2				2
frameshift	30	45				75
splice donor/acceptor (+/-2bp)	2	24				26
Total	40	104	109	191	1

Highest pathogenic variant AF is 0.00026826328

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MPI	protein_coding	protein_coding	ENST00000352410	8	9453

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.17e-7	0.576	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.153	219	225	0.971	0.0000124	2766
Missense in Polyphen		70	73.437	0.9532		849
Synonymous	0.901	82	93.1	0.881	0.00000515	855
Loss of Function	1.03	13	17.7	0.735	8.62e-7	209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000271	0.000271
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000163	0.000163
South Asian	0.000196	0.000196
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.
• Pathway: Fructose and mannose metabolism - Homo sapiens (human);Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Fructose intolerance, hereditary;Fructose and Mannose Degradation;Fructosuria;Aminosugars metabolism;Fructose Mannose metabolism;Post-translational protein modification;Metabolism of proteins;D-mannose degradation;Synthesis of GDP-mannose;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation;GDP-mannose biosynthesis (Consensus)

Recessive Scores

• pRec: 0.622

Intolerance Scores

• loftool: 0.265
• rvis_EVS: -0.16
• rvis_percentile_EVS: 42.06

Haploinsufficiency Scores

• pHI: 0.147
• hipred: N
• hipred_score: 0.204
• ghis: 0.533

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.757

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mpi
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: mpi
• Affected structure: mandibular arch skeleton
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: cell wall mannoprotein biosynthetic process;protein glycosylation;GDP-mannose biosynthetic process;mannose to fructose-6-phosphate metabolic process
• Cellular component: cytosol;extracellular exosome
• Molecular function: mannose-6-phosphate isomerase activity;zinc ion binding