MIF
protein-codingmacrophage migration inhibitory factor
Gene summary
This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. It plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate an additional role in integrin signaling pathways. [provided by RefSeq, Jul 2008]
- GLIF
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~0.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009061
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0011429
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MIF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002415.2. 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 | 2 | ||||
| missense | 21 | 1 | 22 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 21 | 3 | 0 | 24 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002406.1 | 3 | MANE Select | |
| Ensembl | ENSP00000215754.7 | 3 | MANE Select | |
| Ensembl | ENSP00000527291.1 | 3 | Standard | |
| Ensembl | ENSP00000527291.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mif | Danio rerio | Structure: retinal bipolar neuron Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Phenylalanine metabolism - Homo sapiens (human)
- Tyrosine metabolism - Homo sapiens (human)
- Tyrosinemia, transient, of the newborn
- Dopamine beta-hydroxylase deficiency
- Disulfiram Action Pathway
Biological Process
- prostaglandin biosynthetic process
- negative regulation of mature B cell apoptotic process
- inflammatory response
- cell surface receptor signaling pathway
- cell aging
Molecular Function
- protease binding
- dopachrome isomerase activity
- signaling receptor binding
- cytokine activity
- cytokine receptor binding
Cellular Component
- extracellular region
- extracellular space
- nucleoplasm
- cytosol
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000215754
- Coding exons
- 3
- Length
- 1224
- Individuals with no LoFs
- 124687
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 124692
- p
- 0.0000200
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.399 | 75 | 65.9 | 1.14 | 0.00000296 | 723 |
| Missense (PolyPhen) | 24 | 16.679 | 1.439 | 235 | ||
| Synonymous | -0.861 | 37 | 30.9 | 1.20 | 0.00000147 | 225 |
| Loss of Function | 0.506 | 3 | 4.11 | 0.731 | 1.76e-7 | 44 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000054 | 0.000045 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti- inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity. {ECO:0000269|PubMed:15908412, ECO:0000269|PubMed:17443469, ECO:0000269|PubMed:23776208}.;
- Disease
- DISEASE: Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An inflammatory articular disorder with systemic- onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. {ECO:0000269|PubMed:11508429}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. {ECO:0000305}.;
Recessive Scores
- pRec
- 0.375
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |