MFRP (Membrane Frizzled-Related Protein)
A key regulator of eye development and retinal homeostasis; mutations cause nanophthalmos and posterior microphthalmia.
Gene Information Card
| Symbol | MFRP |
|---|---|
| Full Name | Membrane Frizzled-Related Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 11q23.3 |
| NCBI Gene ID | 83552 ncbi.nlm.nih.gov/gene/83552 |
| Ensembl ID | ENSG00000135778 |
| UniProt ID | Q9BYB4 |
| OMIM ID | 606227 |
| HGNC ID | 18168 |
| Aliases | MFRP, CTRP5, MFRP1 |
Description
MFRP encodes the membrane frizzled-related protein, a member of the frizzled-related protein family that contains a cysteine-rich domain (CRD) homologous to the Wnt-binding domain of frizzled receptors. The protein is predominantly expressed in the retinal pigment epithelium (RPE) and ciliary body, where it plays a critical role in eye development, particularly in regulating axial length and photoreceptor function. Mutations in MFRP are associated with autosomal recessive nanophthalmos (NNO1) and posterior microphthalmia, often accompanied by retinitis pigmentosa or foveoschisis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nanophthalmos 1 (NNO1) | Loss-of-function mutations in MFRP disrupt Wnt signaling regulation, leading to reduced axial length and hyperopia. | OMIM #609549; Sundin et al., 2005 |
| Posterior microphthalmia with retinitis pigmentosa | Biallelic MFRP variants impair RPE and photoreceptor interaction, causing retinal degeneration and small posterior segment. | OMIM #611040; Ayala-Ramirez et al., 2006 |
| Foveoschisis | MFRP mutations can lead to splitting of retinal layers at the fovea, likely due to structural RPE defects. | ClinVar; case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Retina | 12.5 | High |
| Retinal pigment epithelium | 15.2 | High |
| Ciliary body | 8.3 | Medium |
| Testis | 2.1 | Low |
| Brain | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (RPE cell line) | 14.8 | High expression |
| HeLa | 0.3 | Very low |
| HEK293 | 0.2 | Very low |
| HepG2 | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.498_499insC (p.Gln167Profs*24) | Frameshift | Rare (founder in European populations) | Loss of function; causes nanophthalmos |
| c.545G>A (p.Arg182Gln) | Missense | Rare | Impaired protein folding; associated with posterior microphthalmia |
| c.1120C>T (p.Arg374*) | Nonsense | Rare | Premature stop; loss of function |
| c.1A>G (p.Met1?) | Start loss | Rare | No protein production; severe nanophthalmos |
Mutation functional classification
Loss of Function (LOF)
Most MFRP mutations are loss-of-function (frameshift, nonsense, start loss), leading to haploinsufficiency or complete absence of functional protein, resulting in nanophthalmos and retinal degeneration.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MFRP.
Dominant Negative (DN)
No dominant-negative mechanisms have been described; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• Retina development (KEGG: hsa04310)
Protein Summary
MFRP is a 579-amino acid transmembrane protein with an N-terminal signal peptide, a cysteine-rich domain (CRD) similar to frizzled receptors, and a C-terminal transmembrane domain. It is expressed on the basolateral surface of RPE cells and is thought to modulate Wnt signaling by binding Wnt ligands or interacting with Frizzled receptors. The protein is essential for normal eye growth and retinal integrity; its loss leads to reduced axial length and photoreceptor dysfunction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MFRP Knockout HEK293 Cell Line | EDJ-KQ9862 | Human | 83552 | Details Get a Quote |
| MFRP Knockout HeLa Cell Line | EDJ-KQ57452 | Human | 83552 | Details Get a Quote |
| MFRP Knockout A-549 Cell Line | EDJ-KQ65956 | Human | 83552 | Details Get a Quote |
| MFRP Knockout HCT 116 Cell Line | EDJ-KQ74379 | Human | 83552 | Details Get a Quote |
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