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The Human Proteome > Tissue specific

The human tissue specific proteome

All approximately 20000 human genes are classified according to their expression across a large number of tissues representing all major organs and tissue types in the human body. Almost half of the genes appear as housekeeping genes with detectable levels of transcripts in all analyzed tissues, while approximately 36% show some level of elevated expression in one of the analyzed tissues. The genes with an elevated expression in a particular tissue or organ are of course interesting as starting points to understand the biology and function of this part of the human body, although only a few of these genes show a strict tissue-specific expression in a single tissue or organ. Functional analysis of the tissue elevated proteins is well in line with the function of the respective tissue or organ with the pancreas, salivary gland, liver and bone marrow expressing a large number of secreted proteins, the kidney expressing membrane-bound transport proteins and the brain expressing many proteins involved in nerve cell function.

  • 2489 tissue enriched genes
  • 1161 group enriched genes
  • A total of 7100 genes are elevated in at least one of the analyzed tissues
  • Elevated genes encode proteins with functions that correspond well to the overall function of the respective organ

Based on transcriptomics analysis across all major organs and tissue types in the human body, all putative 19692 protein-coding genes are classified according to their pattern of protein expression, including 8588 genes expressed in all tissues (see housekeeping proteome) and those expressed in a differential manner across the human body. Of particular interest are those 7100 proteins showing a significant elevated level of expression in a particular tissue or a group of related tissues. These genes consist of three major subclasses (see Table 1 below); the tissue enriched genes (n=2489), the group enriched genes (n=1161) and the tissue enhanced genes (n=3450).

Figure 1. Pie chart showing the number of genes in the different RNA-based categories of gene expression.

Table 1. The genes with elevated expression


Number of genes


Tissue enriched 2489 At least five-fold higher mRNA levels in a particular tissue as compared to all other tissues
Group enriched 1161 At least five-fold higher mRNA levels in a group of 2-7 tissues
Tissue enhanced 3450 At least five-fold higher mRNA levels in a particular tissue as compared to average levels in all tissues
Total 7100 Total number of elevated genes

The amount of tissue elevated genes is highly variable between the analyzed tissue types (see Table 2 below). The testis shows the largest number of tissue enriched genes (n=1057), followed by the brain (n=381) and the liver (n=170). The large number of genes elevated in testis might in part be due to that the corresponding meiosis specific stage in females have not been analyzed. Some tissues have similar functions and tissue morphology and as expected, tissue elevated genes are predominantly group-enriched genes exemplified by hematopoietic tissues, including spleen and lymph node, and the gastrointestinal tract, including duodenum, small intestine and colon.

Table 2. Tissue elevated genes.






Testis 1057 349 574 1980
Cerebral cortex 381 245 597 1223
Fallopian tube 66 201 217 484
Liver 170 135 131 436
Skin 95 123 194 412
Kidney 70 148 179 397
Small intestine 6 180 153 339
Bone marrow 84 46 207 337
Skeletal muscle 106 124 100 330
Duodenum 6 179 135 320
Placenta 83 66 163 312
Esophagus 48 110 139 297
Tonsil 7 101 158 266
Adrenal gland 38 91 129 258
Lymph node 0 50 206 256
Heart muscle 33 120 95 248
Spleen 8 56 170 234
Thyroid gland 28 62 134 224
Stomach 31 63 102 196
Colon 0 108 88 196
Lung 20 53 117 190
Prostate 21 60 105 186
Rectum 1 95 77 173
Adipose tissue 26 43 98 167
Salivary gland 40 49 68 157
Gallbladder 7 46 95 148
Ovary 7 24 114 145
Appendix 2 53 88 143
Endometrium 4 38 72 114
Urinary bladder 6 33 68 107
Pancreas 37 27 31 95
Smooth muscle 1 22 62 85
Total 2489 1161 3450 7100

Tissue enriched genes

The comprehensive analysis presented here has identified approximately 3650 human genes that display a tissue or group-enriched expression pattern across the human body. Functional analysis of the corresponding tissue-enriched proteins identified in our analysis is well in line with the overall function of the respective tissue or organ. Thus, the kidney-enriched proteome (n=70) consists of many membrane-bound transport proteins, such as SLC22A8 (organic anion transporter) and AQP2 (collecting duct water channel protein) whereas the most abundant tissue-enriched proteins in liver (n=170) are secreted plasma proteins, such as ALB (albumin) and HP (haptoglobin), and detoxification proteins, such as UGT2B4 (a member of the UDP glucuronosyltransferase family of enzymes) and a large number of proteins belonging to the cytochrome P450 superfamily of enzymes, such as CYP2A13. Highly expressed brain-enriched proteins are glial cell specific proteins such as the astrocyte intermediate filament protein GFAP (glial fibrillary acidic protein) and major constituents of the myelin sheath, including the oligodendrocyte protein MBP (myelin basic protein), as well as transmembrane proteins associated to synaptic vesicles, such as SLC17A7 (a solute carrier family protein). Moreover, the most abundant pancreas-enriched proteins are digestive enzymes, such as CTRB2 (chymotrypsinogen B2) and AMY2A (amylase, alpha 2A), expressed at extraordinary high levels with over 50000 mRNA molecules per cell, whereas the highest abundance of pancreas-enriched proteins derrived from the endocrine cells in islets of Langerhans include INS (insulin) and GCG (glucagon). Other examples of tissue type specific proteins with a direct link to tissue function include the fat-enriched proteins involved in lipid metabolism, such as PLIN1 (Perilipin 1) and FABP4 (fatty acid-binding protein, adipocyte), skin-enriched proteins involved in squamous differentiation and skin barrier function, such as KRT1 (keratins 1) and CASP14 (caspase-14), and testis-enriched proteins involved in meiosis and spermatogenesis, including DMRT1 (Doublesex- and mab-3-related transcription factor 1) and PRM1 (protamin 1).

The antibody-based protein profiling using immunohistochemistry allows for visualization of where in the body proteins that correspond to different tissue elevated genes are expressed and provides a precise map of protein expression in the various compartments and cell types that constitute different tissues and organs.

Below are examples of protein expression patterns of mainly known and well characterized tissue- and group-enriched genes.

FABP4 - adipose tissue (soft tissue)
PLIN1 - adipose tissue (breast)
HSD3B2 - adrenal gland

PNMT - adrenal gland
CD19 - appendix
MPO - bone marrow

DEFA1 - bone marrow
GFAP - cerebral cortex
MBP - hippocampus

KRT20 - colon
DEFA5 - duodenum
FABP2 - duodenum

CRNN - esophagus
KRT4 - esophagus
CHST4 - gallbladder

TNNI3 - heart muscle
TNNT2 - heart muscle
AQP2 - kidney

UMOD - kidney
ALB - liver
HP - liver

SFTPA1 - lung
SFTPB - lung
CD22 - lymph node

MS4A1 - lymph node
MUM1L1 - ovary
AMY2A - pancreas

INS - pancreas
CSH1 - placenta
KLK3 - prostate

STATH - salivary gland
MYH1 - skeletal muscle
KRT1 - skin

FABP6 - small intestine
CD72 - spleen
PGA3 - stomach

DMRT1 - testis
PRM2 - testis
TG - thyroid gland

TSHR - thyroid gland
UPK2 - urinary bladder
PAEP - endometrium

Figure 2. Examples of protein expression (brown color) patterns of mainly well-known and characterized tissue- and group-enriched genes.

Table 3. Tissue-specific scores and mRNA levels (measured as FPKM) are given for the above selected examples of tissue type enriched proteins.




Tissue specific

mRNA level

Adipose tissue PLIN1 perilipin 1 45 642.0
Adrenal gland HSD3B2 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 557 1546.1
Adrenal gland PNMT phenylethanolamine N-methyltransferase 28 115.6
Appendix CD19 CD19 molecule 9* 24.3
Bone marrow DEFA1 defensin, alpha 1 601 17289.6
Bone marrow MPO myeloperoxidase 273 2067.0
Duodenum DEFA5 defensin, alpha 5, Paneth cell-specific 487* 8868.8
Duodenum FABP2 fatty acid binding protein 2, intestinal 11* 189.7
Endometrium PAEP progestagen-associated endometrial protein 14* 157.9
Esophagus CRNN cornulin 16 3300.2
Esophagus KRT4 keratin 4 13 5749.0
Gallbladder CHST4 carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 4 12 64.1
Heart muscle TNNI3 troponin I type 3 (cardiac) 1771 2776.6
Heart muscle TNNT2 troponin T type 2 (cardiac) 235 4013.8
Kidney AQP2 aquaporin 2 (collecting duct) 186 296.5
Kidney UMOD uromodulin 1339 1627.0
Liver ALB albumin 210 73775.7
Liver HP haptoglobin 127 15456.5
Lung SFTPA1 surfactant protein A1 1459 6613.8
Lung SFTPB surfactant protein B 877 3276.2
Lymph node MS4A1 membrane-spanning 4-domains, subfamily A, member 1 13* 562.2
Ovary MUM1L1 melanoma associated antigen (mutated) 1-like 1 9 163.4
Pancreas AMY2A amylase, alpha 2A (pancreatic) 133 17135.9
Pancreas INS insulin 53 1810.6
Placenta CSH1 chorionic somatomammotropin hormone 1 (placental lactogen) 399 11433.5
Prostate KLK3 kallikrein-related peptidase 3 1301 7370.4
Skeletal muscle MYH1 myosin, heavy chain 1, skeletal muscle, adult 596 1657.6
Skin KRT1 keratin 1 426 8529.2
Small intestine FABP6 fatty acid binding protein 6, ileal 52 2540.8
Spleen CD72 CD72 molecule 7* 42.6
Stomach PGA3 pepsinogen 3, group I (pepsinogen A) 953 9076.1
Testis DMRT1 doublesex and mab-3 related transcription factor 1 83 33.8
Testis PRM2 protamine 2 5950 4757.6
Thyroid gland TG thyroglobulin 1295 8446.6
Thyroid gland TSHR thyroid stimulating hormone receptor 194 223.2
Urinary bladder UPK2 uroplakin 2 50 50.8

* group enriched score for tissue types with similar function and morphology.

In addition to previously known proteins, the analysis also identified a large number of genes with tissue elevated expression patterns that were previously poorly characterized and with no or only scarce evidence of existence on the protein level. The combined RNA- and antibody-based profiling can thus be used to confirm the functional existence of such protein-coding genes lacking previous annotation. These proteins are interesting starting points for further in-depth studies to gain better molecular understanding of the cellular phenotypes that define the function of each respective tissue and organ.

Group enriched proteins

The 1161 genes identified with a group enriched expression pattern reflects genes with shared expression in a limited number of tissues. The function of corresponding proteins may be involved in various traits that can be shared between cell types located in different tissues and organs, such as proteins expressed in inflammatory cells (dominating cell type in lymph node and appendix), proteins involved in squamous differentiation (esophagus and skin), glandular cell function in the gut (duodenum, small intestine and colon) or cilia movement (testis and fallopian tube). The schematic network plot below shows the distribution between tissues of genes with shared expression of group enriched genes.

Figure 3. An interactive network plot of theátissueáenriched and group enriched genes connected to their respective enriched tissues (grey circles).áRedánodes represent the number ofátissue enriched genes andáorangeánodes represent the number of genes that are group enriched. The sizes of the red and orange nodes are related to the number of genes displayed within the node. Each node is clickable and results in a list of all enriched genes connected to the highlighted edges. The network is limited to group enriched genes in combinations of up toá4átissues, but the resulting lists show the complete set of group enriched genes in the particular tissue.

Tissue enhanced genes

The category tissue enhanced genes presents specific lists for each included tissue-type and is defined as genes that do not fulfill the criteria of tissue enriched but show a 5-fold higher FPKM level in a specific tissue type compared to the average FPKM value of all 32 analyzed tissue types.

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Kampf et al (2014). Defining the human gallbladder proteome by transcriptomics and affinity proteomics. Proteomics.
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Lindskog et al (2014). The lung-specific proteome defined by integration of transcriptomics and antibody-based profiling. FASEB J.
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Gremel et al (2014). The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling. J Gastroenterol.
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Kampf et al (2014). The human liver-specific proteome defined by transcriptomics and antibody-based profiling. FASEB J.
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Djureinovic et al (2014). The human testis-specific proteome defined by transcriptomics and antibody-based profiling. Mol Hum Reprod.
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Fagerberg et al (2014). Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics.
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Microscopical images of normal tissue - Tissue Dictionary (Human Protein Atlas)

RNA-seq atlas




Allen Brain Atlas

The human tissue specific proteome
Tissue enriched genes
Group enriched proteins
Tissue enhanced genes
Relevant links and publications