HOPX
protein-codingHOP homeobox, the group of PRD class homeoboxes and pseudogenes
Gene summary
The protein encoded by this gene is a homeodomain protein that lacks certain conserved residues required for DNA binding. It was reported that choriocarcinoma cell lines and tissues failed to express this gene, which suggested the possible involvement of this gene in malignant conversion of placental trophoblasts. Studies in mice suggest that this protein may interact with serum response factor (SRF) and modulate SRF-dependent cardiac-specific gene expression and cardiac development. Multiple alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Feb 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.9 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 HOPX variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032495.6. 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 | 1 | ||||
| missense | 17 | 2 | 19 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 19 | 2 | 1 | 22 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115884.4 | 3 | MANE Select | |
| Ensembl | ENSP00000396275.1 | 3 | MANE Select | |
| RefSeq | NP_001138931.1 | 2 | Standard | |
| RefSeq | NP_001138932.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hopx | Danio rerio | Structure: whole organism Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- hop pathway in cardiac development
Biological Process
- trophectodermal cell differentiation
- regulation of transcription by RNA polymerase II
- negative regulation of cell differentiation
- chaperone-mediated protein complex assembly
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- protein binding
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000554144
- Coding exons
- 4
- Length
- 33911
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125724
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.219 | 52 | 56.6 | 0.918 | 0.00000261 | 726 |
| Missense (PolyPhen) | 3 | 3.4492 | 0.86976 | 35 | ||
| Synonymous | 0.519 | 21 | 24.3 | 0.866 | 0.00000133 | 202 |
| Loss of Function | -0.743 | 7 | 5.18 | 1.35 | 2.19e-7 | 68 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00046 | 0.00043 | rare |
| 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) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00020 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development. Acts via its interaction with SRF, thereby modulating the expression of SRF-dependent cardiac-specific genes and cardiac development. Prevents SRF-dependent transcription either by inhibiting SRF binding to DNA or by recruiting histone deacetylase (HDAC) proteins that prevent transcription by SRF. Overexpression causes cardiac hypertrophy (By similarity). May act as a tumor suppressor. Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and assists in chaperone-mediated protein refolding (PubMed:27708256). {ECO:0000250|UniProtKB:Q8R1H0, ECO:0000269|PubMed:27708256}.;
Recessive Scores
- pRec
- 0.181
Intolerance Scores
- LoFtool
- 0.437
- RVIS EVS
- 0.17
- RVIS percentile EVS
- 65.33
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.310
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |