Alternative titles; symbols
HGNC Approved Gene Symbol: EPB41L1
Cytogenetic location: 20q11.23 Genomic coordinates (GRCh38): 20:36,091,414-36,232,799 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 20q11.23 | ?Intellectual developmental disorder, autosomal dominant 11 | 614257 | Autosomal dominant | 3 |
Erythrocyte membrane protein band 4.1 (EPB41; 130500) is a multifunctional protein that mediates interactions between the erythrocyte cytoskeleton and the overlying plasma membrane. By screening human brain cDNAs for the potential to encode proteins larger than 100 kD, Nagase et al. (1997) identified a partial EPB41L1 cDNA. The 6,263-bp cDNA contains an open reading frame encoding 934 amino acids; it may lack 5-prime coding sequence. The predicted polypeptide is 46% identical to EPB41 across 670 amino acids. By SDS-PAGE, the in vitro transcribed/translated product of the cDNA had a molecular mass of greater than 100 kD. RT-PCR detected EPB41L1 expression in several human tissues.
By radiation hybrid mapping and somatic cell hybrid analysis, Kim et al. (1998) localized the EPB41L1 gene to 20q11.2-q12.
In a 6-year-old boy with intellectual developmental disorder-11 (MRD11; see 614257), Hamdan et al. (2011) identified a de novo heterozygous missense mutation (P85S; 602879.0001) in the EPB41L1 gene, which is located within the critical region for chromosome 20q11-q12 deletion syndrome.
In a 6-year-old by with severely impaired intellectual development (MRD11; see 614257), Hamdan et al. (2011) identified a heterozygous c.2560C-T transition in the EPB41L1 gene (c.2560C-T, NM_012156.2) that resulted in a pro854-to-ser (P854S) substitution. The patient had hypotonia, no evidence of epilepsy, and normal brain imaging by MRI. 4.1N is a neuronal cytoskeletal protein, which binds to AMPA receptor subunits through its C-terminal domain and regulates their expression at the synaptic membrane (Lin et al., 2009, Shen et al., 2000). Hamdan et al. (2011) showed that substitution of proline for serine at position 854 results in a 50% reduction of binding of 4.1N to GLUR1 (138248) compared to wildtype.
Hamdan, F. F., Gauthier, J., Araki, Y., Lin, D.-T., Yoshizawa, Y., Higashi, K., Park, A.-R., Spiegelman, D., Dobrzeniecka, S., Piton, A., Tomitori, H., Daoud, H., and 22 others. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am. J. Hum. Genet. 88: 306-316, 2011. Note: Erratum: Am. J. Hum. Genet. 88: 516 only, 2011. [PubMed: 21376300] [Full Text: https://doi.org/10.1016/j.ajhg.2011.02.001]
Kim, A. C., Van Huffel, C., Lutchman, M., Chishti, A. H. Radiation hybrid mapping of EPB41L1, a novel protein 4.1 homologue, to human chromosome 20q11.2-q12. Genomics 49: 165-166, 1998. [PubMed: 9570967] [Full Text: https://doi.org/10.1006/geno.1998.5212]
Lin, D.-T., Makino, Y., Sharma, K., Hayashi, T., Neve, R., Takamiya, K., Huganir, R. L. Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation. Nature Neurosci. 12: 879-887, 2009. [PubMed: 19503082] [Full Text: https://doi.org/10.1038/nn.2351]
Nagase, T., Ishikawa, K., Nakajima, D., Ohira, M., Seki, N., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 4: 141-150, 1997. [PubMed: 9205841] [Full Text: https://doi.org/10.1093/dnares/4.2.141]
Shen, L., Liang, F., Walensky, L. D., Huganir, R. L. Regulation of AMPA receptor GluR1 subunit surface expression by 4.1N-linked actin cytoskeletal association. J. Neurosci. 20: 7932-7940, 2000. [PubMed: 11050113] [Full Text: https://doi.org/10.1523/JNEUROSCI.20-21-07932.2000]