HOMER3
protein-codinghomer scaffold protein 3, the group of Homer scaffold proteins
Gene summary
This gene encodes a member of the HOMER family of postsynaptic density scaffolding proteins that share a similar domain structure consisting of an N-terminal Enabled/vasodilator-stimulated phosphoprotein homology 1 domain which mediates protein-protein interactions, and a carboxy-terminal coiled-coil domain and two leucine zipper motifs that are involved in self-oligomerization. The encoded protein binds numerous other proteins including group I metabotropic glutamate receptors, inositol 1,4,5-trisphosphate receptors and amyloid precursor proteins and has been implicated in diverse biological functions such as neuronal signaling, T-cell activation and trafficking of amyloid beta peptides. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.1 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 HOMER3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004838.4. 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 | 2 | 4 | ||
| missense | 70 | 1 | 71 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 75 | 2 | 2 | 79 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004829.3 | 9 | MANE Select | |
| Ensembl | ENSP00000376162.2 | 9 | MANE Select | |
| RefSeq | NP_001139193.1 | 9 | Standard | |
| RefSeq | NP_001139194.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutamatergic synapse - Homo sapiens (human)
- FoxO signaling pathway - Homo sapiens (human)
- TCR
- Neuronal System
- Neurexins and neuroligins
Biological Process
- protein targeting
- G protein-coupled glutamate receptor signaling pathway
- negative regulation of interleukin-2 production
- negative regulation of calcineurin-NFAT signaling cascade
- regulation of store-operated calcium entry
Molecular Function
- protein binding
- G protein-coupled glutamate receptor binding
- identical protein binding
Cellular Component
- cellular_component
- cytoplasm
- cytosol
- plasma membrane
- postsynaptic density
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000539827
- Coding exons
- 9
- Length
- 12061
- Individuals with no LoFs
- 112413
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 112414
- p
- 0.00000445
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.19 | 159 | 207 | 0.767 | 0.0000136 | 2266 |
| Missense (PolyPhen) | 57 | 70.033 | 0.8139 | 836 | ||
| Synonymous | 1.80 | 65 | 86.3 | 0.753 | 0.00000564 | 722 |
| Loss of Function | 3.55 | 2 | 18.5 | 0.108 | 9.50e-7 | 202 |
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 | 0.000052 | 0.000052 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. Isoforms can be differently regulated and may play an important role in maintaining the plasticity at glutamatergic synapses. Negatively regulates T cell activation through negative regulation of IL2 expression by inhibiting calcineurin-NFAT pathway activation through interaction with NFATC2 leading to reduction of interaction between NFATC2 and PPP3CA (PubMed:18218901). {ECO:0000269|PubMed:18218901}.;
Recessive Scores
- pRec
- 0.138
Intolerance Scores
- LoFtool
- 0.168
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.649
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |