CD74
protein-codingCD74 molecule, the group of CD molecules
Gene summary
The protein encoded by this gene associates with class II major histocompatibility complex (MHC) and is an important chaperone that regulates antigen presentation for immune response. It also serves as cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF) which, when bound to the encoded protein, initiates survival pathways and cell proliferation. This protein also interacts with amyloid precursor protein (APP) and suppresses the production of amyloid beta (Abeta). Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
- DHLAG
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.3 kbGenCC 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 CD74 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001025159.3. 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 | 1 | 1 | ||||
| missense | 33 | 3 | 36 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 43 | 4 | 0 | 47 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001020330.1 | 9 | MANE Select | |
| Ensembl | ENSP00000009530.7 | 9 | MANE Select | |
| RefSeq | NP_001020329.1 | 5 | Standard | |
| RefSeq | NP_001351012.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Antigen processing and presentation - Homo sapiens (human)
- Tuberculosis - Homo sapiens (human)
- Herpes simplex infection - Homo sapiens (human)
- Macrophage markers
- Macrophage markers
Biological Process
- activation of MAPK activity
- prostaglandin biosynthetic process
- positive regulation of protein phosphorylation
- positive regulation of cytokine-mediated signaling pathway
- positive regulation of dendritic cell antigen processing and presentation
Molecular Function
- amyloid-beta binding
- cytokine receptor activity
- protein binding
- cytokine binding
- MHC class II protein complex binding
Cellular Component
- Golgi membrane
- lysosomal membrane
- multivesicular body
- vacuole
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000009530
- Coding exons
- 9
- Length
- 11293
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125747
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 125 | 177 | 0.704 | 0.0000103 | 1932 |
| Missense (PolyPhen) | 41 | 67.553 | 0.60693 | 706 | ||
| Synonymous | 0.457 | 67 | 71.9 | 0.931 | 0.00000451 | 552 |
| Loss of Function | 2.81 | 4 | 16.2 | 0.246 | 7.89e-7 | 184 |
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) | 0.000027 | 0.000026 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF.;
- Disease
- DISEASE: Note=A chromosomal aberration involving CD74 is found in a non-small cell lung tumor. Results in the formation of a CD74- ROS1 chimeric protein. {ECO:0000269|PubMed:12661006}.;
Recessive Scores
- pRec
- 0.354
Intolerance Scores
- LoFtool
- 0.116
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.990