CD164
protein-codingCD164 molecule, the group of CD molecules
Gene summary
This gene encodes a transmembrane sialomucin and cell adhesion molecule that regulates the proliferation, adhesion and migration of hematopoietic progenitor cells. The encoded protein also interacts with the C-X-C chemokine receptor type 4 and may regulate muscle development. Elevated expression of this gene has been observed in human patients with Sezary syndrome, a type of blood cancer, and a mutation in this gene may be associated with impaired hearing. [provided by RefSeq, Oct 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019587
Submitter: ClinGen
*CD164* was first reported in relation to autosomal dominant nonsyndromic hearing loss (AD NSHL) in 2015 (Nyegaard et al., PMID: 26197441). One pathogenic nonsense variant has been reported in 4 probands in 3 publications (PMIDs: 26197441, 35254497, 36454368). This variant was detected in families from different genetic ancestry groups which suggests that the Arg192 residue is a mutational hotspot, rather than a founder variant. This variant was found to segregate in 24 additional family members in two families (PMID: 26197441, 35254497). This gene disease relationship is also supported by expression and protein interaction studies (PMID: 26197441). In summary there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease association. This gene-disease pair was originally evaluated by the ClinGen Hearing Loss GCEP on 3/20/2018 as per SOP v6. It was reevaluated on 6/25/2024 using SOP v10. As a result of this reevaluation, new case level evidence has been reviewed or added, but the classification did not change (PMIDs: 35254497, 36454368, 36597107).
Inheritance Pattern: AD
Disease ID:MONDO:0019587
Submitter: Orphanet
Inheritance Pattern: Unknown
Disease ID:MONDO:0014854
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic
Intervention: Audiologic/Otolaryngologic
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CD164 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006016.6. 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 | 16 | 2 | 19 | ||
| missense | 61 | 9 | 70 | |||
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 1 | 68 | 25 | 2 | 96 |
Highest pathogenic variant AF is 0.0000013693209
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006007.2 | 6 | MANE Select | |
| Ensembl | ENSP00000309376.4 | 6 | MANE Select | |
| RefSeq | NP_001135873.1 | 5 | Standard | |
| RefSeq | NP_001135874.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cd164 | Danio rerio | Structure: whole organism Quality: increased curvature abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Lysosome - Homo sapiens (human)
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in leukocytes - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
Biological Process
- immune response
- cell adhesion
- heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
- negative regulation of cell adhesion
- signal transduction
Molecular Function
- protein binding
Cellular Component
- extracellular region
- lysosome
- lysosomal membrane
- endosome
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000310786
- Coding exons
- 6
- Length
- 16046
- Individuals with no LoFs
- 124558
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124559
- p
- 0.00000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.257 | 106 | 98.8 | 1.07 | 0.00000489 | 1226 |
| Missense (PolyPhen) | 60 | 60.489 | 0.99191 | 750 | ||
| Synonymous | -0.361 | 42 | 39.1 | 1.07 | 0.00000204 | 406 |
| Loss of Function | 2.39 | 2 | 10.3 | 0.195 | 5.85e-7 | 112 |
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 | 0.000055 | 0.000055 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Sialomucin that may play a key role in hematopoiesis by facilitating the adhesion of CD34(+) cells to the stroma and by negatively regulating CD34(+)CD38(lo/-) cell proliferation. Modulates the migration of umbilical cord blood CD133+ cells and this is mediated through the CXCL12/CXCR4 axis. May play an important role in prostate cancer metastasis and the infiltration of bone marrow by cancer cells. Promotes myogenesis by enhancing CXCR4-dependent cell motility. Positively regulates myoblast migration and promotes myoblast fusion into myotubes (By similarity). {ECO:0000250|UniProtKB:Q9R0L9, ECO:0000269|PubMed:16859559, ECO:0000269|PubMed:17077324, ECO:0000269|PubMed:9763543}.;
- Disease
- DISEASE: Deafness, autosomal dominant, 66 (DFNA66) [MIM:616969]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:26197441}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.115
Intolerance Scores
- LoFtool
- 0.423
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.379
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |