Table 8.

List of linking DEGs with gene expression pattern and synopsis involved in the intercomorbidity association.

Symbol	Name	Gene type	Gene expression	Synopsis	Reference
PBX2	PBX homeobox 2	Protein coding	Downregulated	PBX2 is a member of the TALE/PBX homeobox family that regulates TLX1 promoter translocation in acute pre-B-cell leukemias.	[129]
HSD11B1	Hydroxysteroid 11-beta dehydrogenase 1	Protein coding	Upregulated	HSD11B1 encodes a microsomal enzyme that catalyzes the conversion of cortisone to cortisol and stress hormone cortisol. A high level of cortisol can result in obesity.	[130]
HLA-DRA	Major histocompatibility complex, class II, DR alpha	Protein coding	Upregulated	The HLA class II molecule HLA-DRA plays a key role in the immune system and responses to pathogen-derived peptides.	[131]
UCHL1	Ubiquitin C-terminal hydrolase L1	Protein coding	Upregulated	In neurons and diffuse neuroendocrine system cells, the UCHL1 gene is expressed. Mutations in this gene are associated with Parkinson's disease.	[132]
LENG8	Leukocyte receptor cluster member 8	Protein coding	Downregulated	Among the tissues, the LENG8 gene is expressed in the spleen, endometrium, testis, small intestine, and other areas and is predicted to be functional in the nucleus.	[133]
HSPA1L	Heat shock protein family A (Hsp70) member 1 like	Protein coding	Downregulated	HSPA1L is found in the histocompatibility complex class III region and encodes a 70 kDa heat shock protein. Together with other heat shock proteins, it stabilizes existing proteins.	[134]
CXCL8	C-X-C motif chemokine ligand 8	Protein coding	Upregulated	CXCL8 encodes a protein that is a member of the CXC chemokine family and is referred to as interleukin-8 (IL-8). It is a major mediator of the inflammatory response and plays a role in the proinflammatory signaling cascade, systemic inflammatory response syndrome, lower respiratory tract infection bronchiolitis, lung inflammation, coronary artery disease, endothelial dysfunction, and metastasis.	[135]
HLA-B	Major histocompatibility complex, class I, B	Protein coding	Upregulated	HLA-B is a member of the HLA class I which plays a vital role by presenting peptides derived from the endoplasmic reticulum lumen in the immune system.	[136]
KANSL1	KAT8 regulatory NSL complex subunit 1	Protein coding	Downregulated	The nuclear protein KANSL1 is expressed in the brain, testis, kidney, ovary, thyroid, and other tissues. Moreover, it is a part of two protein complexes including histone acetylation, the NSL1 complex and the MLL1 complex.	[137]
TRIM26	Tripartite motif containing 26	Protein coding	Downregulated	TRIM26 belongs to the tripartite motif (TRIM) family and is found in cytoplasmic bodies. In addition, DNA binding is assumed to be a function of this protein.	[138]
MMP8	Matrix metallopeptidase 8	Protein coding	Upregulated	MMP8 is a member of the matrix metalloproteinase (MMP) family, which is involved in embryonic development, reproduction, tissue remodeling, and disease processes (arthritis and metastasis).	[139]
PLA2G7	Phospholipase A2 group VII	Protein coding	Upregulated	The protein PLA2G7 is a secreted enzyme that catalyzes and causes the degradation of platelet-activating factors into biological inactive products.	[140]
FSTL3	Follistatin like 3	Protein coding	Upregulated	FSTL3 is a glycoprotein in the follistatin-module-protein family that may promote leukemogenesis.	[141]
STC2	Stanniocalcin 2	Protein coding	Upregulated	Homodimeric glycoprotein STC2 is expressed in various tissues and may play a role in regulating renal and intestinal calcium, phosphate transport, cell metabolism, cellular calcium/phosphate homeostasis, and autocrine or paracrine functions.	[142]
BCL2A1	BCL2 related protein A1	Protein coding	Upregulated	BCL2A1 is a member of the BCL-2 protein family that forms heterodimers and homodimers and is involved in cellular activities like embryonic development, homeostasis, and tumorigenesis.	[143]
PIK3C2G	Phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma	Protein coding	Downregulated	The protein PIK3C2G belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases are involved in protein-protein interactions, several diseases (type II diabetes), and signaling pathways including cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking.	[144]
FIBIN	Fin bud initiation factor homolog	Protein coding	Downregulated	FIBIN can be found in the Golgi apparatus, endoplasmic reticulum, or extracellular region. It activates protein homodimerization and protein kinase C signaling as well as responses to dexamethasone and manganese ions.	[145]
CHRNA1	Cholinergic receptor nicotinic alpha 1 subunit	Protein coding	Upregulated	The CHRNA1 gene is expressed in the prostate, colon, lymph nodes, and other tissues and participates in acetylcholine binding and channel gating.	[146]
NPNT	Nephronectin	Protein coding	Downregulated	NPNT is found in extracellular exosomes as well as in collagen-containing extracellular matrix. It is involved in several processes including cell-cell adhesion, positive regulation of osteoblasts, and the ERK1 and ERK2 cascade.	[147]
MEOX1	Mesenchyme homeobox 1	Protein coding	Upregulated	MEOX1 is expressed in fat, heart, spleen, urinary bladder, and other tissues that may influence the molecular signaling network.	[148]
POU2F2	POU class 2 homeobox 2	Protein coding	Upregulated	The POU2F2 gene encodes a homeobox protein of the POU domain family that binds the octamer transcription factor.	[149]
PTPRQ	Protein tyrosine phosphatase receptor type Q	Protein coding	Downregulated	PTPRQ locus is from the type III receptor-like protein-tyrosine phosphatase family that promotes dephosphorylation and phosphatidylinositol and influences cellular proliferation and differentiation.	[150]
SSUH2	Ssu-2 homolog	Protein coding	Upregulated	Its expression can be found in the testes, small intestines, duodenums, and cytoplasms as well as in the nucleus. Again, SSUH2 plays a role in odontogenesis.	[151]
CILP2	Cartilage intermediate layer protein 2	Protein coding	Upregulated	CILP2 is found in extracellular exosomes as well as in the testis, gall bladder, bone marrow, and other tissues.	[152]
CDH2	Cadherin 2	Protein coding	Upregulated	CDH2 is a classical cadherin protein that belongs to the cadherin superfamily. It contributes to the development of the nervous system, left-right asymmetry, cartilage, and bone structure.	[153]
ABCA12	ATP binding cassette subfamily A member 12	Protein coding	Upregulated	ABCA12 is a membrane-associated protein from the ATP-binding cassette (ABC) transporter family. Molecules are transferred within extra and intracellular membranes by ABC proteins.	[154]
CPXM1	Carboxypeptidase X, M14 family member 1	Protein coding	Upregulated	CPXM1 expresses in the endometrium, gall bladder, urinary bladder, and other tissues and encodes a protein of the carboxypeptidase family.	[155]
L1CAM	L1 cell adhesion molecule	Protein coding	Upregulated	The L1CAM axonal glycoprotein belongs to the immunoglobulin supergene family, which can be involved in the development of the nervous system, neural migration, and differentiation.	[156]
ARG2	Arginase 2	Protein coding	Upregulated	ARG2 is expressed in the thyroid, prostate, kidney, and other tissues that facilitate the hydrolysis of arginine into urea and amino acids.	[157]
PTPRH	Protein tyrosine phosphatase receptor type H	Protein coding	Upregulated	PTPRH is usually present in the brain and liver, cancer cells, and at lower levels in the heart and stomach, where it influences several cellular processes such as cell growth, differentiation, the mitotic cycle, and oncogenic transformation. It belongs to the protein tyrosine phosphatase (PTP) group.	[158]
CBSL	Cystathionine beta-synthase like	Protein coding	Upregulated	CBSL homotetramer catalyzes homocysteine to cystathionine conversion and involves in cellular H2S production. Deficiencies of this gene are responsible for cystathionine beta-synthase deficiency which causes homocystinuria.	[159, 160]
GSTM1	Glutathione S-transferase mu 1	Protein coding	Downregulated	GSTM1 belongs to the mu class that encodes a glutathione S-transferase as well as functions in carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress.	[161]
FKBP5	FKBP prolyl isomerase 5	Protein coding	Downregulated	FKBP5 is found in fat, lymph node, esophagus, and other tissues and belongs to the immunophilin protein family, which is involved in immunoregulation and fundamental cellular mechanisms like protein folding and trafficking.	[162]
MCEMP1	Mast cell expressed membrane protein 1	Protein coding	Downregulated	MCEMP1 is a single-pass transmembrane protein, which is biasedly expressed in the lung, bone marrow, appendix, and other tissues. It is hypothesized that MCEMP1 is involved in cell differentiation or immune responses.	[163]
OSCAR	Osteoclast-associated Ig-like receptor	Protein coding	Downregulated	The gene encodes the leukocyte receptor complex protein that is associated with osteoclasts. The gene is associated with bone homeostasis, innate and adaptive immune responses, oxidative stress-mediated atherogenesis, and monocyte adhesion.	[164]
CHD5	Chromodomain helicase DNA binding protein 5	Protein coding	Upregulated	CHD5 is a neuron-specific protein from the chromodomain helicase DNA-binding protein family that is responsible for neuroblastoma development. It may also involve in chromatin remodeling and gene transcription.	[165]
SPATA13	Spermatogenesis-associated 13	Protein coding	Downregulated	SPATA13 is involved in cell migration, migration regulation, plasma membrane-bound cell projection assembly, identical protein binding activity, and guanyl-nucleotide exchange activity. Meanwhile, it is expressed in the spleen, lymph node, appendix, kidney, and other tissues.	[166]