HOMER1
protein-codinghomer scaffold protein 1, the group of Homer scaffold proteins
Gene summary
This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~141.5 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 HOMER1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004272.5. 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 | 2 | 3 | |||
| missense | 22 | 22 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 24 | 1 | 2 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004263.1 | 9 | MANE Select | |
| Ensembl | ENSP00000334382.6 | 9 | MANE Select | |
| RefSeq | NP_001264006.1 | 6 | Standard | |
| RefSeq | NP_001264007.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| homer1b | Danio rerio | Structure: post-vent region Quality: shortened abnormal |
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)
- BDNF-TrkB Signaling
- Neuronal System
- Neurexins and neuroligins
Biological Process
- skeletal muscle contraction
- phospholipase C-activating G protein-coupled glutamate receptor signaling pathway
- G protein-coupled glutamate receptor signaling pathway
- chemical synaptic transmission
- positive regulation of signal transduction
Molecular Function
- protein binding
- G protein-coupled glutamate receptor binding
- signaling adaptor activity
- ion channel binding
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
- postsynaptic density
- Z disc
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334082
- Coding exons
- 9
- Length
- 141582
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.43 | 93 | 186 | 0.500 | 0.00000963 | 2329 |
| Missense (PolyPhen) | 19 | 70.259 | 0.27043 | 911 | ||
| Synonymous | 0.834 | 59 | 67.7 | 0.871 | 0.00000342 | 658 |
| Loss of Function | 4.21 | 0 | 20.6 | 0.00 | 9.41e-7 | 248 |
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 | 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. May also couple GRM1 to PI3 kinase through its interaction with AGAP2. Isoform 1 regulates the trafficking and surface expression of GRM5. Isoform 3 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1 to regulate synaptic metabotropic glutamate function. Isoform 3, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development. Forms a high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (By similarity). {ECO:0000250|UniProtKB:Q9Z214}.;
Recessive Scores
- pRec
- 0.168
Intolerance Scores
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.839