Location

The gene is located on the minus strand at 19q13.33 and spans from 50,466,643 to 50,476,753. It is 10,070 bp long.^[5][6]

Gene Neighborhood

In humans, the gene is flanked by the following genes:^[5][6]

• SPIB: putative oncogene that is active in hematopoietic cells ^[7]
• MYBPC2: encodes a structural protein and is actively expressed in striated muscle cells ^[8]
• EMC10: encodes a protein of unknown function ^[9]
• JOSD2: encodes a protein involved in de-ubiquitination^[10]

Location of FAM71E1 on minus f Chromstrand oosome 19 at q13.33.

Promoter

The promoter of FAM71E1 is located on the minus strand from 50,476,094 to 50,477,946 . It is 1,853 bp long.^[11]

Expression

The gene seems to be ubiquitously expressed at low levels throughout the body ^[12][13][14] but has prominent expression in the adult human testis,^[15] followed by lower expression levels in the sperm, oocyte, and brain.^{[16][17][18][19][20]} Age does not have an effect on its expression in the skeletal muscle of males or females.^[21] Its expression is elevated prior to the differentiation of embryonic stem cells into pancreatic islet-like cells.^[22]

Isoforms

The FAM71E1 gene produces two isoforms from alternative splicing. Isoform 1 is 1281 bp long, and isoform 2 is slightly shorter at 1233 bp long.^[23] Both transcript variants have 5 exons, 4 of which are coding exons. The third intron for the isoform 2 transcript is longer than the one found in isoform 1.^[24]

Regulation

The FAM71E1 transcript is regulated by micro-RNAs, such as miR-149, miR-7, miR-125b, miR-125a-5p, miR192-5p, and miR-215.^[25]

Properties

The protein from isoform 1 is 247 amino acids long with a molecular weight of 27.6 kDa. It has a charge of 5.0 and an isoelectric point of 8.9.^[24] It has a domain of unknown function (DUF3699), which is conserved in eukaryotes and has no known pairwise interactions with other domains.^[26] The structure of the protein has 3 alpha helices and 5 beta strands.

Localization

The protein is predicted to localize to the nucleus and thought to be mainly associated with the nucleoli fibrillar center.^[27] It can also be exported to the cytoplasm.^[14]

Paralogs

The FAM71E1 gene is fast evolving. It has the following 8 paralogs: FAM71A, FAM71B, FAM71C, FAM71D, FAM71E2, FAM71F1, FAM71F2, and AC020922.1. FAM71D, FAM71E2 and AC0209221.1 are found in Amniotes and their last common ancestor with FAM71E1 was likely in the ancestor of the Sauria taxon, which includes reptiles and birds. The remaining paralogs are found in mammals and are expressed in organisms from the evolutionary descendants of the lobe-finned fish (Sarcopterygii). Their last common ancestor with FAM71E1 was Coelacanth (Latimeria chalumnae).^[29]

Orthologs

Orthologs of FAM71E1 can be found only in vertebrates, primarily in placental mammals in the Boreoeutheria group and occasionally in a few reptilian species. Reptiles and marsupials are included in the distant homologs, while orthologs in placental animals such as rodents and primates are more closely related to FAM71E1. The gene history contains 27 duplication events and 1 splitting event.^[29]

Mutations

There are no disease-causing mutations associated with this gene,^[31] and it is tolerant towards loss-of-function variants.^[32]

Disease Associations

FAM71E1 has reduced expression in Type 2 diabetes patients and is likely not involved in the disease's pathophysiology.^[33] Its expression is also altered in Parkinson's disease^[34] and several cancers, such as non-triple negative ductal carcinoma in situ,^[35] breast cancer,^[36] pancreatic adenocarcinoma, and colorectal carcinoma.^[34] It is a gene of interest in predicting susceptibility to pneumonia.^[37]