CD44
protein-codingCD44 molecule (Indian blood group), the group of CD molecules|Proteoglycans|Blood group antigens
Gene summary
The protein encoded by this gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. [provided by RefSeq, Jul 2008]
- MIC4
- MDU2
- MDU3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~93.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Hematologic
Intervention: Hematologic
Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CD44 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000610.4. 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 | 3 | 13 | 6 | 22 | ||
| missense | 88 | 4 | 4 | 96 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 99 | 17 | 10 | 126 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000601.3 | 18 | MANE Select | |
| Ensembl | ENSP00000398632.2 | 18 | MANE Select | |
| RefSeq | NP_001001389.1 | 17 | Standard | |
| RefSeq | NP_001001390.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- ECM-receptor interaction - Homo sapiens (human)
- Shigellosis - Homo sapiens (human)
- Proteoglycans in cancer - Homo sapiens (human)
- MicroRNAs in cancer - Homo sapiens (human)
- Hematopoietic cell lineage - Homo sapiens (human)
Biological Process
- inflammatory response
- cell adhesion
- cell-matrix adhesion
- extracellular matrix disassembly
- extracellular matrix organization
Molecular Function
- transmembrane signaling receptor activity
- cytokine receptor activity
- protein binding
- collagen binding
- hyaluronic acid binding
Cellular Component
- Golgi apparatus
- cytosol
- plasma membrane
- integral component of plasma membrane
- microvillus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000428726
- Coding exons
- 18
- Length
- 93533
- Individuals with no LoFs
- 125637
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 110
- Defined
- 125747
- p
- 0.000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.842 | 358 | 406 | 0.882 | 0.0000206 | 4882 |
| Missense (PolyPhen) | 84 | 116.28 | 0.72241 | 1369 | ||
| Synonymous | -0.0275 | 145 | 145 | 1.00 | 0.00000775 | 1399 |
| Loss of Function | 3.25 | 18 | 40.2 | 0.448 | 0.00000206 | 461 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.0011 | 0.0011 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0023 | 0.0023 | notable |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00019 | 0.00019 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for hyaluronic acid (HA). Mediates cell-cell and cell-matrix interactions through its affinity for HA, and possibly also through its affinity for other ligands such as osteopontin, collagens, and matrix metalloproteinases (MMPs). Adhesion with HA plays an important role in cell migration, tumor growth and progression. In cancer cells, may play an important role in invadopodia formation. Also involved in lymphocyte activation, recirculation and homing, and in hematopoiesis. Altered expression or dysfunction causes numerous pathogenic phenotypes. Great protein heterogeneity due to numerous alternative splicing and post-translational modification events. Receptor for LGALS9; the interaction enhances binding of SMAD3 to the FOXP3 promoter, leading to up-regulation of FOXP3 expression and increased induced regulatory T (iTreg) cell stability and suppressive function (By similarity). {ECO:0000250|UniProtKB:P15379, ECO:0000269|PubMed:16541107}.;
Recessive Scores
- pRec
- 0.949
Intolerance Scores
- LoFtool
- 0.890
- RVIS EVS
- 0.23
- RVIS percentile EVS
- 68.52
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.492
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |