CD244
protein-codingCD244 molecule, the group of CD molecules|Ig-like cell adhesion molecule family|Immunoglobulin like domain containing
Gene summary
This gene encodes a cell surface receptor expressed on natural killer (NK) cells (and some T cells) that mediate non-major histocompatibility complex (MHC) restricted killing. The interaction between NK-cell and target cells via this receptor is thought to modulate NK-cell cytolytic activity. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.7 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 CD244 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016382.4. 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 | 1 | 1 | ||||
| missense | 38 | 10 | 2 | 50 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 38 | 10 | 3 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057466.1 | 9 | MANE Select | |
| Ensembl | ENSP00000357013.4 | 9 | MANE Select | |
| RefSeq | NP_001160135.1 | 9 | Standard | |
| RefSeq | NP_001160136.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Natural killer cell mediated cytotoxicity - Homo sapiens (human)
- Cell surface interactions at the vascular wall
- Hemostasis
Biological Process
- adaptive immune response
- natural killer cell activation involved in immune response
- signal transduction
- innate immune response
- leukocyte migration
Molecular Function
- protein binding
- signaling receptor activity
- MHC class I protein binding
Cellular Component
- plasma membrane
- external side of plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368033
- Coding exons
- 9
- Length
- 32743
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125746
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.301 | 179 | 191 | 0.939 | 0.00000929 | 2423 |
| Missense (PolyPhen) | 32 | 49.909 | 0.64117 | 666 | ||
| Synonymous | -0.431 | 81 | 76.2 | 1.06 | 0.00000404 | 700 |
| Loss of Function | 2.97 | 6 | 20.5 | 0.292 | 9.74e-7 | 233 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Heterophilic receptor of the signaling lymphocytic activation molecule (SLAM) family; its ligand is CD48. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Acts as activating natural killer (NK) cell receptor (PubMed:10359122, PubMed:8376943, PubMed:11714776). Activating function implicates association with SH2D1A and FYN (PubMed:15713798). Downstreaming signaling involves predominantly VAV1, and, to a lesser degree, INPP5D/SHIP1 and CBL. Signal attenuation in the absence of SH2D1A is proposed to be dependent on INPP5D and to a lesser extent PTPN6/SHP-1 and PTPN11/SHP-2 (PubMed:10934222, PubMed:15713798). Stimulates NK cell cytotoxicity, production of IFN-gamma and granule exocytosis (PubMed:8376943, PubMed:11714776). Optimal expansion and activation of NK cells seems to be dependent on the engagement of CD244 with CD48 expressed on neighboring NK cells (By similarity). Acts as costimulator in NK activation by enhancing signals by other NK receptors such as NCR3 and NCR1 (PubMed:10741393). At early stages of NK cell differentiation may function as an inhibitory receptor possibly ensuring the self- tolerance of developing NK cells (PubMed:11917118). Involved in the regulation of CD8(+) T-cell proliferation; expression on activated T-cells and binding to CD488 provides costimulatory-like function for neighboring T-cells (By similarity). Inhibits inflammatory responses in dendritic cells (DCs) (By similarity). {ECO:0000250|UniProtKB:Q07763, ECO:0000269|PubMed:10359122, ECO:0000269|PubMed:10741393, ECO:0000269|PubMed:10934222, ECO:0000269|PubMed:11714776, ECO:0000269|PubMed:11917118, ECO:0000269|PubMed:8376943, ECO:0000305|PubMed:15713798}.;
Recessive Scores
- pRec
- 0.275
Intolerance Scores
- LoFtool
- 0.727
- RVIS EVS
- 0.37
- RVIS percentile EVS
- 75.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.000358
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |