Alt. symbols: HNFJ4 | HSEC61 | SEC61 | SEC61A

Approved name: SEC61 translocon subunit alpha 1
Alt. names: Sec61 alpha 1 subunit (S. cerevisiae)

Location: 3q21.3: 128051641 - 128071705 (+)
Gene type: protein_coding, 22 transcripts.

Scores: LoFtool: 0.035800 | pLI: 0.99560807 | LOEUF: 0.295

HGNC: 18276

NCBI: 29927, RefSeq: NG_052786.1

Ensembl: ENSG00000058262.11

LRG_ | Status: none

OMIM: 609213

Expression | ProteinAtlas

SEC61A1 encodes the alpha (largest) subunit of the ER translocon. The translocon is a protein complex that co-translationally or post-translationally transports nascent polypeptides from the cytosol into the ER lumen or inserts them into the ER membrane. It is a heterotrimeric complex composed of the Sec61-alpha1 subunit and the much smaller Sec61-beta and Sec61-gamma subunits. In its passive state it also functions as a calcium (Ca+2) leakage channel, but in its open state, the Sec61 channel forms a large aqueous pore in the ER membrane that is also penetrable for small molecules and ions.

Monoallelic LoF mutations in this gene were initially reported (2016) to cause a type of autosomal dominant nephropathy named as familial juvenile hyperuricemic nephropathy 4 by OMIM (#617056), with only one patient presenting with neutropenia (PMID: 27392076). In 2018, 2 mutations were reported to also lead to a predominantly antibody deficiency phenotype without neutropenia (PMID: 28782633). More recently (2020), another mutation in this gene were reported to cause severe congenital neutropeni a in 1 boy without hypogammaglobulinemia or nephropathy (PMID: 32325141). Experimental characterization of these mutants showed reduced protein expression and function leading to altered ER translocation and dysregulated Ca+2 flux. Schubert et al. proposed that the V85D could have a dominant negative effect. [Load More]