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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MPP4
MAGUK p55 scaffold protein 4
Chromosome 2 Β· 2q33.1
NCBI Gene: 58538Ensembl: ENSG00000082126.18HGNC: HGNC:13680UniProt: A0A087WUS1
14PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingadherens junctioncytosolprotein-containing complexIntellectual disabilityStrabismusSeizureHigh palate
✦AI Summary

MPP4 (MAGUK p55 scaffold protein 4) is a retina-specific member of the membrane-associated guanylate kinase (MAGUK) protein family that functions as a molecular scaffold at specialized membrane-cytoskeleton interfaces 1. The protein contains characteristic MAGUK motifs including an N-terminal PDZ domain, SH3 region, and C-terminal guanylate kinase-like domain, placing it in the p55 subfamily 1. MPP4 is abundantly expressed in photoreceptor cells and localizes specifically to connecting cilia and synaptic terminals of both cone and rod photoreceptors, as well as postsynaptic structures in the outer plexiform layer 23. The protein functions by organizing multiprotein complexes at photoreceptor ribbon synapses, interacting with adaptor proteins including Veli3 and Psd95-beta through L27 domain interactions 45. Additional associated proteins include recoverin and Hsc70, suggesting roles in calcium signaling and protein folding at synapses 4. MPP4's location on chromosome 2-33 coincides with the RP26 locus for autosomal recessive retinitis pigmentosa, though mutation screening has not established it as the causative gene 12. The protein's specific localization and scaffolding function suggest it plays a critical role in photoreceptor synapse organization and visual signal transmission.

Sources cited
1
MPP4 is a retina-specific MAGUK family member with PDZ, SH3, and GUK domains, belonging to p55 subfamily
PMID: 11414766
2
MPP4 is highly expressed in photoreceptor cells and maps to chromosome 2q31-33 near RP26 locus
PMID: 12384283
3
MPP4 protein localizes to connecting cilia and synaptic terminals of photoreceptors and postsynaptic structures
PMID: 14638699
4
MPP4 forms protein complexes including Veli3, Psd95-beta, recoverin, and Hsc70 at photoreceptor synapses
PMID: 18955048
5
MPP4 interacts with Veli3 via L27 domains and localizes to photoreceptor synaptic terminals
PMID: 15558731
Disease Associationsβ“˜20
Generalized hypotoniaOpen Targets
0.33Weak
Global developmental delayOpen Targets
0.33Weak
High palateOpen Targets
0.33Weak
Intellectual disabilityOpen Targets
0.33Weak
SeizureOpen Targets
0.33Weak
StrabismusOpen Targets
0.33Weak
Wide nasal bridgeOpen Targets
0.33Weak
tricuspid valve diseaseOpen Targets
0.27Weak
male reproductive system diseaseOpen Targets
0.15Weak
cervical carcinomaOpen Targets
0.10Weak
metabolic syndromeOpen Targets
0.07Suggestive
age-related macular degenerationOpen Targets
0.07Suggestive
X-linked retinal dysplasiaOpen Targets
0.06Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.06Suggestive
retinitis pigmentosaOpen Targets
0.05Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.05Suggestive
Stargardt diseaseOpen Targets
0.05Suggestive
reticular dystrophy of the retinal pigment epitheliumOpen Targets
0.05Suggestive
Familial drusenOpen Targets
0.04Suggestive
X-linked retinoschisisOpen Targets
0.04Suggestive
Pathogenic Variants1
NM_033066.3(MPP4):c.946T>C (p.Trp316Arg)Pathogenic
7 conditions
β˜†β˜†β˜†β˜†β†’ Residue 316
View on ClinVar β†—
Related Genes
GRK7Protein interaction100%PALS1Protein interaction93%ITPR2Protein interaction75%RCVRNProtein interaction75%GRK1Protein interaction75%COLQShared pathway50%
Tissue Expression6 tissues
Ovary
100%
Liver
81%
Lung
76%
Brain
52%
Heart
44%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
MPP4GRK7PALS1ITPR2RCVRNGRK1COLQ
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q96JB8
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.10LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.89 [0.72–1.10]
RankingsWhere MPP4 stands among ~20K protein-coding genes
  • #15,930of 20,598
    Most Researched14
  • #5,444of 5,498
    Most Pathogenic Variants1
  • #11,235of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedMPP4
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Cloning and characterization of the human retina-specific gene MPP4, a novel member of the p55 subfamily of MAGUK proteins.
PMID: 11414766
Genomics Β· 2001
1.00
2
CXCR4 signaling determines the fate of hematopoietic multipotent progenitors by stimulating mTOR activity and mitochondrial metabolism.
PMID: 39471249
Sci Signal Β· 2024
0.90
3
Characterization of MPP4, a gene highly expressed in photoreceptor cells, and mutation analysis in retinitis pigmentosa.
PMID: 12384283
Gene Β· 2002
0.80
4
Identification and characterization of human MPP7 gene and mouse Mpp7 gene in silico.
PMID: 14719143
Int J Mol Med Β· 2004
0.70
5
Cellular localization of the MPP4 protein in the mammalian retina.
PMID: 14638699
Invest Ophthalmol Vis Sci Β· 2003
0.60