Pih1d2, without commonly known aliases from the provided references, is involved in multiple biological processes. It is part of the R2SP complex, along with SPAG1, RUVBL1, and RUVBL2, which functions in quaternary protein folding, especially in testis [6,8]. Pih1d2 may also play a role in cilia/flagella motions and the assembly of axonemal dyneins as shown in zebrafish mutants [9].

In male infertility, Pih1d2 was among 56 genes commonly differentially expressed between non-obstructive azoospermia (NOA) and non-obstructive and obstructive azoospermia (NOA and OA) groups. These genes are involved in germ cell development, spermatid development, spermatid differentiation, regulation of proteolysis, spermatogenesis, and metabolic processes [1]. In renal papillary cell carcinoma, Pih1d2 was one of six RNA-binding proteins screened out to establish a prognostic model [2]. In cervical cancer, high expression of Pih1d2 indicated a better prognosis [7]. A chromosome 11q deletion encompassing Pih1d2 was detected in a patient with a sympathetic head and neck paraganglioma [3]. In juvenile snakeskin gourami, Pih1d2 was a male-biased differentially expressed gene associated with testis differentiation [4]. Pih1d2 along with MRPS33 and SD1HD was associated with increased type 2 diabetes risk through paternal genetic nurture effects [5].

In conclusion, Pih1d2 is crucial for processes like protein folding in testis, cilia/flagella-related functions, and has implications in multiple disease conditions including male infertility, renal and cervical cancers, paraganglioma, and type 2 diabetes. Studies on Pih1d2, especially through genetic models like zebrafish mutants, have enhanced our understanding of its functions in various biological processes and diseases.

References:

1. Omolaoye, Temidayo S, Omolaoye, Victor A, Kandasamy, Richard K, Hachim, Mahmood Yaseen, Du Plessis, Stefan S. 2022. Omics and Male Infertility: Highlighting the Application of Transcriptomic Data. In Life (Basel, Switzerland), 12, . doi:10.3390/life12020280. https://pubmed.ncbi.nlm.nih.gov/35207567/

2. Jiang, Silin, Ren, Xiaohan, Liu, Shouyong, Qin, Chao, Wang, Zengjun. 2021. Integrated Analysis of the Prognosis-Associated RNA-Binding Protein Genes and Candidate Drugs in Renal Papillary Cell Carcinoma. In Frontiers in genetics, 12, 627508. doi:10.3389/fgene.2021.627508. https://pubmed.ncbi.nlm.nih.gov/33643390/

3. Cadiñanos, Juan, Llorente, José L, de la Rosa, Jorge, Murias, Eduardo, Cabanillas, Rubén. 2010. Novel germline SDHD deletion associated with an unusual sympathetic head and neck paraganglioma. In Head & neck, 33, 1233-40. doi:10.1002/hed.21384. https://pubmed.ncbi.nlm.nih.gov/20310044/

4. Boonanuntanasarn, Surintorn, Jangprai, Araya, Na-Nakorn, Uthairat. 2020. Transcriptomic analysis of female and male gonads in juvenile snakeskin gourami (Trichopodus pectoralis). In Scientific reports, 10, 5240. doi:10.1038/s41598-020-61738-0. https://pubmed.ncbi.nlm.nih.gov/32251302/

5. Li, Xiaoyi, Zhou, Zechen, Ma, Yujia, Chen, Dafang, Wu, Yiqun. 2025. Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design. In Biomedicines, 13, . doi:10.3390/biomedicines13010120. https://pubmed.ncbi.nlm.nih.gov/39857704/

6. Maurizy, Chloé, Quinternet, Marc, Abel, Yoann, Manival, Xavier, Bertrand, Edouard. 2018. The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones. In Nature communications, 9, 2093. doi:10.1038/s41467-018-04431-1. https://pubmed.ncbi.nlm.nih.gov/29844425/

7. Liu, Xue, Li, Wei, Yang, Chun, Luo, Judong, Tang, Bin. 2025. Cuproptosis-related genes signature could predict prognosis and the response of immunotherapy in cervical cancer. In Translational cancer research, 14, 129-140. doi:10.21037/tcr-24-641. https://pubmed.ncbi.nlm.nih.gov/39974424/

8. Chagot, Marie-Eve, Dos Santos Morais, Raphael, Dermouche, Sana, Dehez, François, Quinternet, Marc. 2019. Binding properties of the quaternary assembly protein SPAG1. In The Biochemical journal, 476, 1679-1694. doi:10.1042/BCJ20190198. https://pubmed.ncbi.nlm.nih.gov/31118266/

9. Yamaguchi, Hiroshi, Oda, Toshiyuki, Kikkawa, Masahide, Takeda, Hiroyuki. 2018. Systematic studies of all PIH proteins in zebrafish reveal their distinct roles in axonemal dynein assembly. In eLife, 7, . doi:10.7554/eLife.36979. https://pubmed.ncbi.nlm.nih.gov/29741156/