GCHFR | ENSG00000137880 | NCBI 2644

Details for: GCHFR

Associated with

Metabolism
(R-HSA-1430728)
Metabolism of cofactors
(R-HSA-8978934)
Metabolism of vitamins and cofactors
(R-HSA-196854)
Tetrahydrobiopterin (bh4) synthesis, recycling, salvage and regulation
(R-HSA-1474151)
Cytoplasm
(GO:0005737)
Cytosol
(GO:0005829)
Dendrite
(GO:0030425)
Gtp cyclohydrolase binding
(GO:0044549)
Melanosome
(GO:0042470)
Negative regulation of biosynthetic process
(GO:0009890)
Nuclear membrane
(GO:0031965)
Nucleoplasm
(GO:0005654)
Nucleus
(GO:0005634)
Protein binding
(GO:0005515)
Regulation of nitric oxide biosynthetic process
(GO:0045428)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

elicited macrophage CL0000861

CSI 65.61

rCSI 60.24%

PRS 75.72
intestinal epithelial cell CL0002563

CSI 55.2

rCSI 57.69%

PRS 64.56
alveolar macrophage CL0000583

CSI 36.58

rCSI 60.25%

PRS 72.01
colonocyte CL1000347

CSI 23.32

rCSI 33.43%

PRS 69.32
stem cell CL0000034

CSI 23.09

rCSI 22.26%

PRS 57.89
transit amplifying cell of colon CL0009011

CSI 21.79

rCSI 25.59%

PRS 68.64
colon epithelial cell CL0011108

CSI 16.62

rCSI 17.41%

PRS 63.3
enterocyte CL0000584

CSI 15.97

rCSI 25.75%

PRS 69.01
M cell of gut CL0000682

CSI 15.43

rCSI 16.4%

PRS 75.2
epithelial cell of proximal tubule CL0002306

CSI 15.29

rCSI 37.35%

PRS 59.67
megakaryocyte-erythroid progenitor cell CL0000050

CSI 12.42

rCSI 11.22%

PRS 63.89
brush cell CL0002204

CSI 11.65

rCSI 23.07%

PRS 80.68
ciliated cell CL0000064

CSI 11.42

rCSI 18.5%

PRS 62.74
club cell CL0000158

CSI 9.42

rCSI 13.8%

PRS 61.93
chondrocyte CL0000138

CSI 9.36

rCSI 14.88%

PRS 59.35
duct epithelial cell CL0000068

CSI 8.8

rCSI 12.88%

PRS 71.55
central memory CD8-positive, alpha-beta T cell CL0000907

CSI 8.75

rCSI 5.89%

PRS 80.31
BEST4+ enteroycte CL4030026

CSI 8.07

rCSI 10.04%

PRS 68.29
promonocyte CL0000559

CSI 8

rCSI 13.71%

PRS 74.98
IgG plasma cell CL0000985

CSI 7.81

rCSI 9.36%

PRS 81.84
myeloid leukocyte CL0000766

CSI 7.69

rCSI 7.1%

PRS 68.51
naive T cell CL0000898

CSI 7.62

rCSI 5.31%

PRS 81.95
mesenchymal cell CL0008019

CSI 7.51

rCSI 19.08%

PRS 60.57
CD16-positive, CD56-dim natural killer cell, human CL0000939

CSI 7.04

rCSI 4.69%

PRS 84.58
transit amplifying cell of small intestine CL0009012

CSI 6.96

rCSI 30.55%

PRS 79.53
acinar cell CL0000622

CSI 6.59

rCSI 9.67%

PRS 77.97
mucus secreting cell CL0000319

CSI 6.42

rCSI 10.2%

PRS 77.09
pulmonary alveolar type 2 cell CL0002063

CSI 6.38

rCSI 9.89%

PRS 73.36
alternatively activated macrophage CL0000890

CSI 6.37

rCSI 8%

PRS 78.19
epithelial cell of lower respiratory tract CL0002632

CSI 6.13

rCSI 4.75%

PRS 69.46
pancreatic D cell CL0000173

CSI 6.1

rCSI 6%

PRS 69.47
pancreatic A cell CL0000171

CSI 5.98

rCSI 6.27%

PRS 70.34
central memory CD4-positive, alpha-beta T cell CL0000904

CSI 5.89

rCSI 3.48%

PRS 83.83
tracheal goblet cell CL1000329

CSI 5.87

rCSI 12.81%

PRS 78.27
metallothionein-positive alveolar macrophage CL4033042

CSI 5.8

rCSI 63.05%

PRS 83.79
enteroendocrine cell of small intestine CL0009006

CSI 5.78

rCSI 12.73%

PRS 78.15
tracheobronchial serous cell CL0019001

CSI 5.69

rCSI 24.58%

PRS 77.9
respiratory suprabasal cell CL4033048

CSI 5.55

rCSI 7.12%

PRS 71.08
lung macrophage CL1001603

CSI 5.17

rCSI 11.54%

PRS 74.48
bronchial goblet cell CL1000312

CSI 5.08

rCSI 20.29%

PRS 80.17
placental villous trophoblast CL2000060

CSI 4.99

rCSI 7.7%

PRS 65.2
epithelial cell CL0000066

CSI 4.89

rCSI 7.52%

PRS 60.48
effector CD4-positive, alpha-beta T cell CL0001044

CSI 4.88

rCSI 13.99%

PRS 85.89
double negative thymocyte CL0002489

CSI 4.82

rCSI 3.35%

PRS 78.22
granulocyte monocyte progenitor cell CL0000557

CSI 4.71

rCSI 4.08%

PRS 71.69
vein endothelial cell of respiratory system CL4033008

CSI 4.5

rCSI 30.89%

PRS 78.3
mature T cell CL0002419

CSI 4.49

rCSI 3.49%

PRS 83.69
CD4-positive, alpha-beta thymocyte CL0000810

CSI 4.47

rCSI 3.58%

PRS 85.27
natural T-regulatory cell CL0000903

CSI 4.42

rCSI 8.38%

PRS 91.85
paneth cell CL0000510

CSI 4.42

rCSI 6.53%

PRS 80.99
peripheral nervous system neuron CL2000032

CSI 4.37

rCSI 5.95%

PRS 58.24
pulmonary artery endothelial cell CL1001568

CSI 4.31

rCSI 5.86%

PRS 77.92
plasmacytoid dendritic cell, human CL0001058

CSI 4.24

rCSI 2.96%

PRS 69.7
mature alpha-beta T cell CL0000791

CSI 4.09

rCSI 14.81%

PRS 85.24
respiratory goblet cell CL0002370

CSI 4.06

rCSI 44.13%

PRS 79.46
germinal center B cell CL0000844

CSI 4

rCSI 11.93%

PRS 81.81
choroid plexus epithelial cell CL0000706

CSI 3.86

rCSI 6.33%

PRS 55.81
CD1c-positive myeloid dendritic cell CL0002399

CSI 3.83

rCSI 4.62%

PRS 75.61
nasal mucosa goblet cell CL0002480

CSI 3.77

rCSI 4.37%

PRS 73.51
secretory cell CL0000151

CSI 3.71

rCSI 3.87%

PRS 66.71
effector CD8-positive, alpha-beta T cell CL0001050

CSI 3.7

rCSI 2.82%

PRS 79.95
CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792

CSI 3.67

rCSI 3.6%

PRS 82.26
T follicular helper cell CL0002038

CSI 3.65

rCSI 2.73%

PRS 81.52
goblet cell CL0000160

CSI 3.58

rCSI 3.39%

PRS 65.75
CD8-positive, alpha-beta thymocyte CL0000811

CSI 3.42

rCSI 5.34%

PRS 88.06
early lymphoid progenitor CL0000936

CSI 3.41

rCSI 2.99%

PRS 72.24
enteroendocrine cell CL0000164

CSI 3.4

rCSI 4.65%

PRS 67.74
activated type II NK T cell CL0000931

CSI 3.19

rCSI 3.59%

PRS 82.76
plasmablast CL0000980

CSI 3.19

rCSI 2.51%

PRS 73.38
intestine goblet cell CL0019031

CSI 3.15

rCSI 2.8%

PRS 64.38
hematopoietic stem cell CL0000037

CSI 3.1

rCSI 2.06%

PRS 69.76
epithelial cell of lung CL0000082

CSI 2.96

rCSI 2.45%

PRS 66.27
lung secretory cell CL1000272

CSI 2.88

rCSI 7.14%

PRS 65.37
multi-ciliated epithelial cell CL0005012

CSI 2.87

rCSI 2.86%

PRS 60.19
Kupffer cell CL0000091

CSI 2.85

rCSI 6.52%

PRS 67
midzonal region hepatocyte CL0019028

CSI 2.81

rCSI 6.6%

PRS 70.02
CD4-positive, alpha-beta memory T cell CL0000897

CSI 2.75

rCSI 1.97%

PRS 80.75
CD8-positive, alpha-beta memory T cell CL0000909

CSI 2.73

rCSI 2.85%

PRS 86.14
activated CD4-positive, alpha-beta T cell CL0000896

CSI 2.71

rCSI 2.51%

PRS 85.08
double-positive, alpha-beta thymocyte CL0000809

CSI 2.68

rCSI 2.73%

PRS 78.69
transit amplifying cell CL0009010

CSI 2.63

rCSI 4.02%

PRS 78.81
lung interstitial macrophage CL4033043

CSI 2.54

rCSI 5.71%

PRS 82.6
myofibroblast cell CL0000186

CSI 2.54

rCSI 3.52%

PRS 66.68
common myeloid progenitor CL0000049

CSI 2.49

rCSI 2.01%

PRS 68.63
basal cell of epithelium of trachea CL1000348

CSI 2.46

rCSI 17.39%

PRS 78.44
type L enteroendocrine cell CL0002279

CSI 2.46

rCSI 4.62%

PRS 79.36
fallopian tube secretory epithelial cell CL4030006

CSI 2.41

rCSI 2.32%

PRS 66.37
bronchus fibroblast of lung CL2000093

CSI 2.32

rCSI 1.89%

PRS 67.1
lung ciliated cell CL1000271

CSI 2.32

rCSI 2.69%

PRS 57.32
respiratory basal cell CL0002633

CSI 2.29

rCSI 2.37%

PRS 72.45
lung resident memory CD8-positive, alpha-beta T cell CL4033039

CSI 2.25

rCSI 5.82%

PRS 89.18
common dendritic progenitor CL0001029

CSI 2.2

rCSI 2.77%

PRS 77.07
myeloid lineage restricted progenitor cell CL0000839

CSI 2.2

rCSI 11.36%

PRS 86.6
hepatocyte CL0000182

CSI 2.2

rCSI 3.93%

PRS 66.18
T-helper 17 cell CL0000899

CSI 2.19

rCSI 1.74%

PRS 86.8
centrilobular region hepatocyte CL0019029

CSI 2.17

rCSI 5.66%

PRS 68.9
conjunctival epithelial cell CL1000432

CSI 2.13

rCSI 3.26%

PRS 67.48
CD4-positive helper T cell CL0000492

CSI 2.06

rCSI 1.56%

PRS 80.27
pulmonary ionocyte CL0017000

CSI 1.98

rCSI 2.42%

PRS 74.13
erythrocyte CL0000232

CSI 1.96

rCSI 4.45%

PRS 69.62

epithelial cell of esophagus CL0002252

CSI 0.2

rCSI 2.0%

PRS 80.7%
erythroid progenitor cell CL0000038

CSI 0.4

rCSI 2.0%

PRS 75.1%
P/D1 enteroendocrine cell CL0002268

CSI 0.4

rCSI 2.1%

PRS 79.8%
enterocyte of epithelium of small intestine CL1000334

CSI 0.4

rCSI 6.8%

PRS 81.0%
enteroendocrine cell of colon CL0009042

CSI 0.5

rCSI 2.3%

PRS 81.4%
CD8-alpha-alpha-positive, alpha-beta intraepithelial T cell CL0000915

CSI 0.6

rCSI 2.6%

PRS 90.2%
intestinal crypt stem cell of colon CL0009043

CSI 0.6

rCSI 4.6%

PRS 80.8%
primitive red blood cell CL0002355

CSI 0.6

rCSI 3.4%

PRS 77.5%
luminal cell of prostate epithelium CL0002340

CSI 0.6

rCSI 3.4%

PRS 77.3%
CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203

CSI 0.6

rCSI 0.8%

PRS 51.8%
pulmonary alveolar type 1 cell CL0002062

CSI 0.6

rCSI 3.7%

PRS 64.7%
paneth cell of epithelium of small intestine CL1000343

CSI 0.7

rCSI 1.9%

PRS 76.7%
helper T cell CL0000912

CSI 0.7

rCSI 1.0%

PRS 70.3%
large pre-B-II cell CL0000957

CSI 0.8

rCSI 2.3%

PRS 76.8%
myelocyte CL0002193

CSI 0.8

rCSI 5.4%

PRS 89.1%
mammary gland epithelial cell CL0002327

CSI 1.0

rCSI 3.3%

PRS 78.1%
intermediate monocyte CL0002393

CSI 1.0

rCSI 1.5%

PRS 71.6%
serous secreting cell of bronchus submucosal gland CL4033005

CSI 1.0

rCSI 5.7%

PRS 83.5%
pancreatic epsilon cell CL0005019

CSI 1.0

rCSI 4.9%

PRS 81.2%
intestinal crypt stem cell of small intestine CL0009017

CSI 1.1

rCSI 2.8%

PRS 73.2%
CD4-positive, alpha-beta cytotoxic T cell CL0000934

CSI 1.3

rCSI 1.7%

PRS 85.1%
intestinal tuft cell CL0019032

CSI 1.3

rCSI 1.9%

PRS 70.8%
paneth cell of colon CL0009009

CSI 1.3

rCSI 12.7%

PRS 81.2%
mucous neck cell CL0000651

CSI 1.3

rCSI 1.9%

PRS 76.4%
CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920

CSI 1.3

rCSI 2.6%

PRS 83.0%
eosinophil CL0000771

CSI 1.3

rCSI 8.6%

PRS 90.4%
retinal cone cell CL0000573

CSI 1.3

rCSI 2.2%

PRS 56.3%
mononuclear phagocyte CL0000113

CSI 1.4

rCSI 3.1%

PRS 70.8%
radial glial cell CL0000681

CSI 1.4

rCSI 2.0%

PRS 65.4%
CD8-positive, alpha-beta cytotoxic T cell CL0000794

CSI 1.5

rCSI 1.7%

PRS 85.1%
T-helper 1 cell CL0000545

CSI 1.5

rCSI 2.6%

PRS 86.7%
type EC enteroendocrine cell CL0000577

CSI 1.5

rCSI 5.3%

PRS 74.0%
CD14-positive, CD16-positive monocyte CL0002397

CSI 1.5

rCSI 2.0%

PRS 79.8%
squamous epithelial cell CL0000076

CSI 1.5

rCSI 3.6%

PRS 69.6%
deuterosomal cell CL4033044

CSI 1.6

rCSI 5.3%

PRS 68.9%
thymocyte CL0000893

CSI 1.6

rCSI 5.8%

PRS 92.3%
promyelocyte CL0000836

CSI 1.7

rCSI 2.4%

PRS 75.3%
alveolar adventitial fibroblast CL4028006

CSI 1.7

rCSI 2.7%

PRS 69.3%
colon goblet cell CL0009039

CSI 1.7

rCSI 4.1%

PRS 74.5%
cytotoxic T cell CL0000910

CSI 1.8

rCSI 10.1%

PRS 75.0%
podocyte CL0000653

CSI 1.8

rCSI 7.9%

PRS 66.7%
effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062

CSI 1.8

rCSI 9.1%

PRS 79.4%
ciliated epithelial cell CL0000067

CSI 1.8

rCSI 1.6%

PRS 54.6%
kidney epithelial cell CL0002518

CSI 1.9

rCSI 3.5%

PRS 84.7%
pancreatic ductal cell CL0002079

CSI 1.9

rCSI 3.7%

PRS 69.7%
ciliated columnar cell of tracheobronchial tree CL0002145

CSI 1.9

rCSI 4.3%

PRS 62.4%
ionocyte CL0005006

CSI 1.9

rCSI 2.1%

PRS 66.8%
erythrocyte CL0000232

CSI 2.0

rCSI 4.5%

PRS 69.6%
pulmonary ionocyte CL0017000

CSI 2.0

rCSI 2.4%

PRS 74.1%
CD4-positive helper T cell CL0000492

CSI 2.1

rCSI 1.6%

PRS 80.3%
conjunctival epithelial cell CL1000432

CSI 2.1

rCSI 3.3%

PRS 67.5%
centrilobular region hepatocyte CL0019029

CSI 2.2

rCSI 5.7%

PRS 68.9%
T-helper 17 cell CL0000899

CSI 2.2

rCSI 1.7%

PRS 86.8%
hepatocyte CL0000182

CSI 2.2

rCSI 3.9%

PRS 66.2%
myeloid lineage restricted progenitor cell CL0000839

CSI 2.2

rCSI 11.4%

PRS 86.6%
common dendritic progenitor CL0001029

CSI 2.2

rCSI 2.8%

PRS 77.1%
lung resident memory CD8-positive, alpha-beta T cell CL4033039

CSI 2.3

rCSI 5.8%

PRS 89.2%
respiratory basal cell CL0002633

CSI 2.3

rCSI 2.4%

PRS 72.5%
lung ciliated cell CL1000271

CSI 2.3

rCSI 2.7%

PRS 57.3%
bronchus fibroblast of lung CL2000093

CSI 2.3

rCSI 1.9%

PRS 67.1%
fallopian tube secretory epithelial cell CL4030006

CSI 2.4

rCSI 2.3%

PRS 66.4%
type L enteroendocrine cell CL0002279

CSI 2.5

rCSI 4.6%

PRS 79.4%
basal cell of epithelium of trachea CL1000348

CSI 2.5

rCSI 17.4%

PRS 78.4%
common myeloid progenitor CL0000049

CSI 2.5

rCSI 2.0%

PRS 68.6%
myofibroblast cell CL0000186

CSI 2.5

rCSI 3.5%

PRS 66.7%
lung interstitial macrophage CL4033043

CSI 2.5

rCSI 5.7%

PRS 82.6%
transit amplifying cell CL0009010

CSI 2.6

rCSI 4.0%

PRS 78.8%
double-positive, alpha-beta thymocyte CL0000809

CSI 2.7

rCSI 2.7%

PRS 78.7%
activated CD4-positive, alpha-beta T cell CL0000896

CSI 2.7

rCSI 2.5%

PRS 85.1%
CD8-positive, alpha-beta memory T cell CL0000909

CSI 2.7

rCSI 2.9%

PRS 86.1%
CD4-positive, alpha-beta memory T cell CL0000897

CSI 2.8

rCSI 2.0%

PRS 80.8%
midzonal region hepatocyte CL0019028

CSI 2.8

rCSI 6.6%

PRS 70.0%
Kupffer cell CL0000091

CSI 2.9

rCSI 6.5%

PRS 67.0%
multi-ciliated epithelial cell CL0005012

CSI 2.9

rCSI 2.9%

PRS 60.2%
lung secretory cell CL1000272

CSI 2.9

rCSI 7.1%

PRS 65.4%
epithelial cell of lung CL0000082

CSI 3.0

rCSI 2.5%

PRS 66.3%
hematopoietic stem cell CL0000037

CSI 3.1

rCSI 2.1%

PRS 69.8%
intestine goblet cell CL0019031

CSI 3.2

rCSI 2.8%

PRS 64.4%
plasmablast CL0000980

CSI 3.2

rCSI 2.5%

PRS 73.4%
activated type II NK T cell CL0000931

CSI 3.2

rCSI 3.6%

PRS 82.8%
enteroendocrine cell CL0000164

CSI 3.4

rCSI 4.7%

PRS 67.7%
early lymphoid progenitor CL0000936

CSI 3.4

rCSI 3.0%

PRS 72.2%
CD8-positive, alpha-beta thymocyte CL0000811

CSI 3.4

rCSI 5.3%

PRS 88.1%
goblet cell CL0000160

CSI 3.6

rCSI 3.4%

PRS 65.8%
T follicular helper cell CL0002038

CSI 3.7

rCSI 2.7%

PRS 81.5%
CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792

CSI 3.7

rCSI 3.6%

PRS 82.3%
effector CD8-positive, alpha-beta T cell CL0001050

CSI 3.7

rCSI 2.8%

PRS 80.0%
secretory cell CL0000151

CSI 3.7

rCSI 3.9%

PRS 66.7%
nasal mucosa goblet cell CL0002480

CSI 3.8

rCSI 4.4%

PRS 73.5%
CD1c-positive myeloid dendritic cell CL0002399

CSI 3.8

rCSI 4.6%

PRS 75.6%
choroid plexus epithelial cell CL0000706

CSI 3.9

rCSI 6.3%

PRS 55.8%
germinal center B cell CL0000844

CSI 4.0

rCSI 11.9%

PRS 81.8%
respiratory goblet cell CL0002370

CSI 4.1

rCSI 44.1%

PRS 79.5%
mature alpha-beta T cell CL0000791

CSI 4.1

rCSI 14.8%

PRS 85.2%
plasmacytoid dendritic cell, human CL0001058

CSI 4.2

rCSI 3.0%

PRS 69.7%
pulmonary artery endothelial cell CL1001568

CSI 4.3

rCSI 5.9%

PRS 77.9%
peripheral nervous system neuron CL2000032

CSI 4.4

rCSI 6.0%

PRS 58.2%
paneth cell CL0000510

CSI 4.4

rCSI 6.5%

PRS 81.0%
natural T-regulatory cell CL0000903

CSI 4.4

rCSI 8.4%

PRS 91.9%
CD4-positive, alpha-beta thymocyte CL0000810

CSI 4.5

rCSI 3.6%

PRS 85.3%

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Interaction Source:

Pathway Categories (for ONTOLOGY source):

Baseline Cell Type:

Baseline Cell Context(s): Comma-separated if multiple.

Target Cell Type:

Target Cell Context(s): Comma-separated if multiple.

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Query Gene
Node Color (Target Cell CSI, relative to current network):
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- High
- Medium
- Low
- Very Low
- CSI N/A
Node Size: Proportional to Target Cell CSI magnitude
STRING PPI Edge
Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

Description
Proteins

## Summary [GCHFR](/details-gene/2644) (GTP Cyclohydrolase I Feedback Regulator) is a protein-coding gene located on chromosome 15q15.1. It encodes a regulatory protein that modulates the activity of GTP cyclohydrolase I, the rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH4). Functionally, [GCHFR](/details-gene/2644) is implicated in the negative regulation of biosynthetic processes, particularly the production of nitric oxide. Expression data from the **Overall** context indicates that [GCHFR](/details-gene/2644) is a significant gene in myeloid cells, such as [elicited macrophage](/details-cell/CL0000861) and [alveolar macrophage](/details-cell/CL0000583), as well as various epithelial cell populations, most notably [intestinal epithelial cell](/details-cell/CL0002563) and [colonocyte](/details-cell/CL1000347). This expression pattern suggests a key role in modulating BH4-dependent pathways within both the innate immune system and mucosal tissues. A clinical association with Dopa-responsive Dystonia has been noted ([OMIM [602437](https://omim.org/entry/602437)]). ## Cellular Roles and Expression Landscape The expression profile of [GCHFR](/details-gene/2644) highlights its importance in distinct cellular lineages, primarily within myeloid and epithelial compartments. **Overall**, the gene shows the highest significance in [elicited macrophage](/details-cell/CL0000861) (CSI: 65.61) and [alveolar macrophage](/details-cell/CL0000583) (CSI: 36.58), suggesting a critical function in macrophage biology, likely related to inflammatory responses and host defense. Concurrently, [GCHFR](/details-gene/2644) is highly significant across a spectrum of gut epithelial cells, including [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 55.20), [colonocyte](/details-cell/CL1000347) (CSI: 23.32), and proliferative [transit amplifying cell of colon](/details-cell/CL0009011) (CSI: 21.79). This strong signal in the intestinal epithelium suggests a role in maintaining mucosal homeostasis, barrier integrity, or regulating cell turnover. Its significance also extends to other specialized epithelial types such as [epithelial cell of proximal tubule](/details-cell/CL0002306) in the kidney and various respiratory epithelial cells like [ciliated cell](/details-cell/CL0000064) and [club cell](/details-cell/CL0000158). The co-expression in both immune and epithelial cells points to a fundamental role in tissues that serve as barriers and are active sites of immune surveillance. ## Pathways and Molecular Function The function of [GCHFR](/details-gene/2644) is centered on the regulation of cofactor metabolism, as annotated in the Reactome pathway database. It is a key component of the '[Tetrahydrobiopterin (bh4) synthesis, recycling, salvage and regulation](https://reactome.org/content/detail/R-HSA-1474151)' pathway. BH4 is an essential cofactor for several enzymes, including nitric oxide synthases (NOS) and aromatic amino acid hydroxylases involved in neurotransmitter synthesis. Consistent with its role in BH4 metabolism, Gene Ontology (GO) annotations link [GCHFR](/details-gene/2644) to the '[Negative regulation of biosynthetic process](https://www.ebi.ac.uk/QuickGO/term/GO:0009890)' and, more specifically, the '[Regulation of nitric oxide biosynthetic process](https://www.ebi.ac.uk/QuickGO/term/GO:0045428)'. This function aligns perfectly with its high expression in macrophages, which utilize NO as a potent antimicrobial agent. By modulating BH4 availability, [GCHFR](/details-gene/2644) can control the magnitude and duration of the NO-mediated inflammatory response. At the molecular level, [GCHFR](/details-gene/2644) exerts its function through direct protein-protein interactions, specifically via '[Gtp cyclohydrolase binding](https://www.ebi.ac.uk/QuickGO/term/GO:0044549)' ([Link](https://pubmed.ncbi.nlm.nih.gov/16696853/)). Cellular localization studies have shown the protein resides in both the '[Cytoplasm](https://www.ebi.ac.uk/QuickGO/term/GO:0005737)' and the '[Nucleus](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)', suggesting it may regulate BH4 synthesis in multiple cellular compartments ([Link](https://pubmed.ncbi.nlm.nih.gov/16778797/)). ## Research Directions The specific expression pattern and established molecular function of [GCHFR](/details-gene/2644) provide a basis for several testable hypotheses regarding its role in health and disease. **Proposed Hypotheses:** 1. **[GCHFR](/details-gene/2644) is a critical regulator of macrophage inflammatory potential.** Its high expression suggests it acts as a rheostat for nitric oxide production in response to pathogens. Downregulation of [GCHFR](/details-gene/2644) in macrophages may lead to excessive BH4 and NO production, contributing to tissue damage in inflammatory conditions like sepsis or inflammatory bowel disease. 2. **In the intestinal epithelium, [GCHFR](/details-gene/2644) contributes to mucosal barrier integrity and cell proliferation.** Its significance in [transit amplifying cell of colon](/details-cell/CL0009011) suggests a role in regulating the balance between epithelial cell renewal and differentiation, potentially through BH4-dependent pathways that are distinct from nitric oxide synthesis. **Suggested Experimental Approach:** To test the first hypothesis regarding macrophage function, a targeted knockdown or knockout of [GCHFR](/details-gene/2644) could be performed in a human monocyte cell line (e.g., THP-1) using CRISPR-Cas9. These genetically modified cells, alongside wild-type controls, would be differentiated into macrophages and subsequently challenged with an inflammatory stimulus like lipopolysaccharide (LPS). Key readouts would include: (i) quantification of nitric oxide production using the Griess assay; (ii) measurement of intracellular BH4 levels via mass spectrometry; and (iii) profiling of pro-inflammatory cytokine secretion (e.g., TNF-alpha, IL-6) using ELISA or multiplex bead arrays. This experiment would directly elucidate the role of [GCHFR](/details-gene/2644) in controlling the macrophage inflammatory program. **Therapeutic Potential:** As an intracellular regulatory protein, [GCHFR](/details-gene/2644) is a potential target for small-molecule therapeutics rather than antibodies. Given its role in modulating NO synthesis, pharmacological **inhibition** of [GCHFR](/details-gene/2644) could be a strategy to enhance antimicrobial responses where NO production is insufficient. Conversely, **activation** or stabilization of its feedback function could be beneficial in hyper-inflammatory states characterized by excessive NO-mediated tissue damage, such as septic shock or certain autoimmune diseases. Any therapeutic strategy would need to carefully consider potential on-target effects in the central nervous system, given the role of BH4 in neurotransmitter synthesis and the gene's link to dystonia.

Disclaimer: This in-silico analysis is generated by an AI language model and may contain inaccuracies or hallucinations. However, it is cross-referenced with curated gene expression data from major biological sources. Please verify the information before use.

GTP cyclohydrolase 1 feedback regulatory protein

Genular Protein ID: 452536174

Symbol: GFRP_HUMAN

Name: GTP cyclohydrolase 1 feedback regulatory protein

UniProtKB Accession Codes:

P30047 B2R4L6 B7ZLM8 Q2M1Q2 Q99749

Database IDs:

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 1286669

Title: Human liver protein map: a reference database established by microsequencing and gel comparison.

PubMed ID: 1286669

DOI: 10.1002/elps.11501301201

PubMed ID: 16778797

Title: GTP cyclohydrolase feedback regulatory protein controls cofactor 6-tetrahydrobiopterin synthesis in the cytosol and in the nucleus of epidermal keratinocytes and melanocytes.

PubMed ID: 16778797

DOI: 10.1038/sj.jid.5700425

PubMed ID: 16696853

Title: A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions.

PubMed ID: 16696853

DOI: 10.1111/j.1471-4159.2006.03836.x

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

Length: 84
Mass: 9698
Checksum: 4A20FDBC6E3EE7AC
Sequence:

MPYLLISTQI RMEVGPTMVG DEQSDPELMQ HLGASKRRAL GNNFYEYYVD DPPRIVLDKL 
ERRGFRVLSM TGVGQTLVWC LHKE

	Overall overall
	Basal cell carcinoma MONDO0020804
	Blood UBERON0000178
	\|— Blood COVID-19 UBERON0000178_MONDO0100096
	\|— Blood Cytomegalovirus infection UBERON0000178_MONDO0005132
	\|— Blood Healthy UBERON0000178_PATO0000461
	Bone marrow UBERON0002371
	Breast UBERON0000310
	\|— Breast cancer MONDO0007254
	Bronchus UBERON0002185
	Caudate lobe of liver UBERON0001117
	Colon UBERON0001155
	\|— Colon Healthy UBERON0001155_PATO0000461
	Colorectal cancer MONDO0005575
	COVID-19 MONDO0100096
	Crohn disease MONDO0005011
	Cytomegalovirus infection MONDO0005132
	Duodenum UBERON0002114
	\|— Duodenum Healthy UBERON0002114_PATO0000461
	Glioblastoma MONDO0018177
	Healthy PATO0000461
	Ileum UBERON0002116
	\|— Ileum Healthy UBERON0002116_PATO0000461
	\|— Ileum lamina propria UBERON8600035
	Islet of Langerhans UBERON0000006
	Kidney UBERON0002113
	\|— Kidney Healthy UBERON0002113_PATO0000461
	Lamina propria of small intestine UBERON0001238
	Liver UBERON0002107
	\|— Liver Healthy UBERON0002107_PATO0000461
	Lung UBERON0002048
	\|— Lung Healthy UBERON0002048_PATO0000461
	\|— Lung adenocarcinoma MONDO0005061
	Malignant ovarian serous tumor MONDO0024885
	Nasopharynx UBERON0001728
	Pleural effusion UBERON0000175
	Retina UBERON0000966
	\|— Retina Healthy UBERON0000966_PATO0000461
	Small cell lung carcinoma MONDO0008433
	Thymus UBERON0002370
	\|— Thymus Healthy UBERON0002370_PATO0000461
	Upper lobe of left lung UBERON0008952

Details for: GCHFR

Cell Significance Landscape

Associated with

Significant Cells

Network Configuration

Legend:

Other Information

Complete sequencing and characterization of 21,243 full-length human cDNAs. PubMed ID: 14702039

Analysis of the DNA sequence and duplication history of human chromosome 15. PubMed ID: 16572171

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). PubMed ID: 15489334

Human liver protein map: a reference database established by microsequencing and gel comparison. PubMed ID: 1286669

GTP cyclohydrolase feedback regulatory protein controls cofactor 6-tetrahydrobiopterin synthesis in the cytosol and in the nucleus of epidermal keratinocytes and melanocytes. PubMed ID: 16778797

A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions. PubMed ID: 16696853

Initial characterization of the human central proteome. PubMed ID: 21269460

An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. PubMed ID: 24275569