LRWD1 Gene (Leucine-Rich Repeats and WD Repeat Domain Containing 1)
Essential regulator of origin recognition complex (ORC) assembly and heterochromatin organization
Gene Information Card
| Symbol | LRWD1 |
|---|---|
| Full Name | Leucine-Rich Repeats and WD Repeat Domain Containing 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 222229 ncbi.nlm.nih.gov/gene/222229 |
| Ensembl ID | ENSG00000106384 |
| UniProt ID | Q9UFC0 |
| OMIM ID | 615167 |
| HGNC ID | 28798 |
| Aliases | ORCA, C7orf14, MGC12966 |
Description
LRWD1 (also known as ORCA) encodes a leucine-rich repeat and WD repeat domain-containing protein that is a component of the origin recognition complex (ORC). It is involved in the assembly of the pre-replication complex and plays a critical role in heterochromatin organization and gene silencing. The protein interacts with ORC subunits and histones, contributing to replication origin licensing and chromatin structure maintenance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (general) | LRWD1 overexpression may promote tumorigenesis by altering replication licensing and heterochromatin stability. | COSMIC; PMID: 25631443 |
| Hepatocellular carcinoma | Upregulation of LRWD1 correlates with poor prognosis and increased cell proliferation. | PMID: 28411369 |
| Breast cancer | LRWD1 expression is associated with estrogen receptor status and may influence cell cycle progression. | PMID: 27397505 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Bone marrow | 8.2 | Medium |
| Lymph node | 7.1 | Medium |
| Brain | 4.3 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney; high expression |
| HeLa | 9.4 | Cervical carcinoma; moderate-high |
| HepG2 | 7.8 | Hepatocellular carcinoma; medium |
| MCF7 | 6.5 | Breast cancer; medium |
| K562 | 5.2 | Leukemia; low-medium |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.01% | Unknown; rare variant in population databases |
| c.1420G>A (p.Glu474Lys) | Missense | <0.01% | Predicted benign by in silico tools |
| c.1876_1878del (p.Lys626del) | In-frame deletion | <0.01% | Reported in COSMIC; functional impact unclear |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in ClinVar or COSMIC for LRWD1.
Gain of Function (GOF)
Overexpression in cancer suggests potential gain-of-function role in promoting proliferation.
Dominant Negative (DN)
No dominant-negative mutations described.
View complete mutation data：
Gene Ontology (GO)
Pathways
• DNA replication (Reactome: R-HSA-69306)
• Assembly of the pre-replicative complex (Reactome: R-HSA-68867)
• Heterochromatin organization (Reactome: R-HSA-2299718)
Protein Summary
The LRWD1 protein (ORCA) contains N-terminal leucine-rich repeats and C-terminal WD40 repeats. It directly binds to ORC2 and ORC3, stabilizing the origin recognition complex on chromatin. LRWD1 also interacts with histone H3 and HP1, facilitating heterochromatin formation and gene silencing. Its expression is cell cycle-regulated, peaking in G1 phase. The protein is essential for proper replication origin licensing and maintenance of genomic stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LRWD1 Knockout HEK293 Cell Line | EDJ-KQ8984 | Human | 222229 | Details Get a Quote |
| LRWD1 Knockout A-549 Cell Line | EDJ-KQ35416 | Human | 222229 | Details Get a Quote |
| LRWD1 Knockout HCT 116 Cell Line | EDJ-KQ35417 | Human | 222229 | Details Get a Quote |
| LRWD1 Knockout HeLa Cell Line | EDJ-KQ35418 | Human | 222229 | Details Get a Quote |
