HFE

Summary

HFE (homeostatic iron regulator, HGNC:4886) is a protein-coding gene on chromosome 6p22.2, encoding Hereditary hemochromatosis protein (Q30201). Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.

The protein encoded by this gene is a membrane protein that is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). It is thought that this protein functions to regulate iron absorption by regulating the interaction of the transferrin receptor with transferrin. The iron storage disorder, hereditary haemochromatosis, is a recessive genetic disorder that results from defects in this gene.

Source: NCBI Gene 3077 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hemochromatosis type 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 149
• Clinical variants (ClinVar): 335 total — 27 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 86
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4886
Approved symbol	HFE
Name	homeostatic iron regulator
Location	6p22.2
Locus type	gene with protein product
Status	Approved
Aliases	HLA-H, HFE1
Ensembl gene	ENSG00000010704
Ensembl biotype	protein_coding
OMIM	613609
Entrez	3077

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 18 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000309234, ENST00000317896, ENST00000336625, ENST00000349999, ENST00000352392, ENST00000353147, ENST00000357618, ENST00000397022, ENST00000461397, ENST00000470149, ENST00000483782, ENST00000485729, ENST00000486147, ENST00000488199, ENST00000714164, ENST00000714168, ENST00000714169, ENST00000714170, ENST00000714171, ENST00000714172, ENST00000714173, ENST00000714174, ENST00000714175, ENST00000714176

RefSeq mRNA: 13 — MANE Select: NM_000410 NM_000410, NM_001300749, NM_001384164, NM_001406751, NM_001406752, NM_139003, NM_139004, NM_139006, NM_139007, NM_139008, NM_139009, NM_139010, NM_139011

CCDS: CCDS4578, CCDS4579, CCDS4580, CCDS4581, CCDS4582, CCDS47386, CCDS47387, CCDS54974, CCDS54975, CCDS75412

Canonical transcript exons

ENST00000357618 — 6 exons

Exon	Start	End
ENSE00001641676	26091314	26091589
ENSE00003535082	26093119	26093232
ENSE00003637434	26090841	26091104
ENSE00004023057	26094186	26098343
ENSE00004023066	26087429	26087516
ENSE00004023067	26092685	26092960

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 94.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.7972 / max 48.4918, expressed in 1171 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66474	1.4626	867
66473	1.3346	872

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	94.02	gold quality
olfactory bulb	UBERON:0002264	93.87	gold quality
stromal cell of endometrium	CL:0002255	86.59	gold quality
choroid plexus epithelium	UBERON:0003911	83.68	gold quality
monocyte	CL:0000576	83.44	gold quality
mononuclear cell	CL:0000842	83.12	gold quality
leukocyte	CL:0000738	82.79	gold quality
right adrenal gland cortex	UBERON:0035827	81.66	gold quality
right adrenal gland	UBERON:0001233	81.42	gold quality
triceps brachii	UBERON:0001509	81.38	gold quality
smooth muscle tissue	UBERON:0001135	81.32	gold quality
cervix epithelium	UBERON:0004801	81.30	silver quality
seminal vesicle	UBERON:0000998	81.02	gold quality
gluteal muscle	UBERON:0002000	81.00	silver quality
left adrenal gland	UBERON:0001234	80.83	gold quality
diaphragm	UBERON:0001103	80.80	gold quality
vena cava	UBERON:0004087	80.72	gold quality
calcaneal tendon	UBERON:0003701	80.50	gold quality
gall bladder	UBERON:0002110	80.37	gold quality
left adrenal gland cortex	UBERON:0035825	80.30	gold quality
adrenal cortex	UBERON:0001235	80.22	gold quality
tongue squamous epithelium	UBERON:0006919	80.15	silver quality
adrenal gland	UBERON:0002369	80.07	gold quality
liver	UBERON:0002107	79.57	gold quality
pancreatic ductal cell	CL:0002079	79.45	silver quality
colonic epithelium	UBERON:0000397	79.40	gold quality
lateral nuclear group of thalamus	UBERON:0002736	79.22	gold quality
rectum	UBERON:0001052	79.10	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.00	gold quality
corpus epididymis	UBERON:0004359	78.64	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	187.65
E-ANND-3	no	4.82

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
BMPR1A	Activation

Upstream regulators (CollecTRI, top): E2F1, KLF5, NKX2-5, PARP1

miRNA regulators (miRDB)

52 targeting HFE, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-6128	99.33	67.83	1581

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• 871 healthy unrelated subjects in Poland were collected to assess the relevant frequencies. Each subject was genotyped for the C282Y and H63D mutations using a PCR-based protocol (PMID:11386022)
• The Ala176Val mutation may have a possible role on the cause of hemochromatosis in a Japanese case (PMID:11446670)
• mutational analysis of the transferrin receptor reveals overlapping HFE and transferrin binding sites (PMID:11800564)
• genotype and allele frequencies between neonates and referred patients for HFE molecular analysis (PMID:11809727)
• Association between MHC class I gene HFE polymorphisms and longevity (PMID:11857056)
• HFE gene implicated in this disorder has been identified on chromosome 6. the most prevalent mutation is a point mutation(histidine to aspartic acid)in iron overload has been controversial. (PMID:11869934)
• A previously undescribed nonsense mutation of the HFE gene (PMID:11903354)
• Distribution of HFE C282Y and H63D mutations in the Balearic Islands (NE Spain). (PMID:11903355)
• results suggest that wild-type HFE negatively modulates the endocytic uptake of transferrin (PMID:11940510)
• Frequency of the S65C mutation of HFE and iron overload in subjects heterozygous for C282Y. (PMID:11943417)
• REVIEW:Characteristics of the C282Y mutation in childhood ALL, in contrast to other cancers, is male-specific, lacks a gene-dosage effect, and exhibits associations suggesting the involvement of another HLA-linked gene in leukemia susceptibility. (PMID:12002748)
• Long term survival is excellent in C282Y homozygotes for the C282Y mutation of the hemochromatosis gene diagnosed and treated before the development of cirrhosis and diabetes (PMID:12045778)
• Individuals with mutations in the HFE gene show very few hemochromatosis-related symptoms. (PMID:12059121)
• The tighter association of the -467 polymorphism with the C282Y mutation is consistent with other data that suggest that the C282Y mutation has occurred relatively recently and that the H63D mutation is considerably older. (PMID:12064915)
• HFE mutations do not confer an additional risk of hepatic fibrosis in patients with nonalcoholic steatohepatitis (PMID:12085358)
• possession of the HFE gene 282Tyr allele may offer some protection against the development of Parkinson Disease. (PMID:12098643)
• polymorphism and its relation to type 2 diabetes mellitus in the Czech population (PMID:12148086)
• When combined with the C282Y mutation, the S65C mutation is associated with an increased risk of hemochromatosis. (PMID:12180078)
• HFE has two mutually exclusive functions, binding to TfR1 in competition with Tf, or inhibition of iron release from macrophages. (PMID:12429850)
• HFE mutations more common in patients than controls, and advanced degrees of fibrosis developed at younger ages with C282Y mutation. Patients with C282Y had higher mean hepatic iron concentrations, hepatic iron indices, and hepatic fibrosis scores. (PMID:12445428)
• These results suggest that the apparent iron-deficient phenotype elicited by haemochromatosis protein (HFE) is not linked to beta(2)microglobulin insufficiency. (PMID:12464008)
• an increased risk of osteoarthritis among individuals who are heterozygous for the C282Y HFE mutation. (PMID:12508400)
• Genotyping of the C282Y and H63D substitutions in the HFE gene provides a satisfactory marker since these genotypes are associated with ~90% of herditary hemochromatosis. (PMID:12512743)
• Subjects with any HFE gene mutation were more likely to have colon cancer than subjects with no HFE gene mutations. (PMID:12529348)
• The presence of HFE mutations is independently associated with iron loading and advanced fibrosis in patients with compensated liver disease from chronic hepatitis C, especially after controlling for duration of disease. (PMID:12557137)
• C282Y or H63D heterozygosity is an independent risk factor for liver fibrosis and cirrhosis in HCV infected individuals. Screening for HFE mutations should be considered in HCV infection. (PMID:12586300)
• Results suggest that the H63D mutation in the hereditary hemochromatosis HFE gene may play a role in the pathogenesis of late onset type 2 diabetes. (PMID:12601293)
• In patients with rheumatoid arthritis, 2/24 (8.34%) were found to be positive for the C282Y mutation in the case of heterozygosis compared with 3/24 (12.5%) of patients with spondylarthritis. (PMID:12635863)
• The presence of TfR2 and absence of TfR1 suggests that HFE may serve a different function in platelets compared with the other HFE-positive cell types. (PMID:12656741)
• Interacts with transferrin receptors in endosomes (PMID:12667138)
• HFE C282Y and H63D are determinants of iron parameters in the elderly and will be effective in detecting individuals at high risk of hemochromatosis. (PMID:12673276)
• HFE and APOE genotypes are different between Alzheimer’s disease patients, high cognitive impairment and low cognitive impairment (PMID:12707938)
• this study does not support the suggestion that H63D mutations may anticipate sporadic AD clinical presentation in susceptible individuals. (PMID:12714262)
• trend for an increased frequency of H63D allele in centenarian women (PMID:12714263)
• In a population of 1279 Caucasians with angiographically confirmed coronary status, there is no evidence of an association between the C282Y mutation in the haemochromatosis gene and prevalence of coronary artery disease and myocardial infarction (PMID:12746412)
• The mild iron overload associated with heterozygosity for C282Y HFE mutation confers susceptibility to nonalcoholic fatty liver disease (PMID:12779071)
• We see no evidence for over-representation of iron loading HFE alleles in type 2 diabetes mellitus (PMID:12783844)
• study performed in two samples of genetically homogeneous patients and controls does not support the suggestion that HFE mutations may be associated with acute myocardial infarction in susceptible individuals (PMID:12850485)
• HFE can lower intracellular iron levels independently of its interaction with the transferrin receptor (PMID:12874382)
• HFE mutations C282Y and H63D carrier rate in an Irish population of cystic fibrosis allele carriers (PMID:12885340)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hfe	ENSMUSG00000006611
rattus_norvegicus	Hfe	ENSRNOG00000016967

Paralogs (22): FCGRT (ENSG00000104870), ULBP1 (ENSG00000111981), ULBP2 (ENSG00000131015), ULBP3 (ENSG00000131019), MR1 (ENSG00000153029), RAET1L (ENSG00000155918), CD1D (ENSG00000158473), CD1A (ENSG00000158477), CD1C (ENSG00000158481), CD1B (ENSG00000158485), CD1E (ENSG00000158488), AZGP1 (ENSG00000160862), RAET1E (ENSG00000164520), RAET1G (ENSG00000203722), MICB (ENSG00000204516), MICA (ENSG00000204520), HLA-C (ENSG00000204525), HLA-E (ENSG00000204592), HLA-G (ENSG00000204632), HLA-F (ENSG00000204642), HLA-A (ENSG00000206503), HLA-B (ENSG00000234745)

Protein

Protein identifiers

Hereditary hemochromatosis protein — Q30201 (reviewed: Q30201)

Alternative names: HLA-H

All UniProt accessions (13): Q30201, A0AAQ5BHI2, A0AAQ5BHJ0, A0AAQ5BHK7, A0AAQ5BHL2, A0AAQ5BHM0, A0AAQ5BHM2, A0AAQ5BHM4, A0AAQ5BHP7, A0AAQ5BHP9, F8W7W8, H7C4K4, Q6B0J5

UniProt curated annotations — full annotation on UniProt →

Function. Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.

Subunit / interactions. Binds TFR through the extracellular domain in a pH-dependent manner.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in all tissues tested except brain.

Disease relevance. Hemochromatosis 1 (HFE1) [MIM:235200] A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. Genetic variations in HFE may influence the transferrin serum levels. Iron is essential for biochemical functions such as oxygen transport and oxidative phosphorylation. Excessive iron can cause iron-overload-related liver diseases, whereas iron deficiency can lead to anemia. Iron status can be assessed by measuring the levels of serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the MHC class I family.

Isoforms (11)

UniProt ID	Names	Canonical?
Q30201-1	1	yes
Q30201-2	2, delE2
Q30201-3	3, del14E4
Q30201-4	4, delE214E4
Q30201-5	5
Q30201-6	6
Q30201-7	7, delE3
Q30201-8	8, 1043-2283del,intron6ins
Q30201-9	9, delE3-7
Q30201-10	10, 562-878del
Q30201-11	11

RefSeq proteins (13): NP_000401, NP_001287678, NP_001371093, NP_001393680, NP_001393681, NP_620572, NP_620573, NP_620575, NP_620576, NP_620577, NP_620578, NP_620579, NP_620580 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001039	MHC_I_a_a1/a2	Domain
IPR003006	Ig/MHC_CS	Conserved_site
IPR003597	Ig_C1-set	Domain
IPR007110	Ig-like_dom	Domain
IPR011161	MHC_I-like_Ag-recog	Domain
IPR011162	MHC_I/II-like_Ag-recog	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037055	MHC_I-like_Ag-recog_sf	Homologous_superfamily
IPR050208	MHC_class-I_related	Family

Pfam: PF00129, PF07654

UniProt features (83 total): sequence variant 19, strand 18, splice variant 13, helix 9, sequence conflict 6, region of interest 4, glycosylation site 3, turn 3, disulfide bond 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1A6Z	X-RAY DIFFRACTION	2.6
1DE4	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q30201-F1	88.62	0.72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 124–187, 225–282

Glycosylation sites (3): 110, 130, 234

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-917977	Transferrin endocytosis and recycling

MSigDB gene sets: 98 (showing top): GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_VIA_MHC_CLASS_IB, GAURNIER_PSMD4_TARGETS, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_POSITIVE_REGULATION_OF_T_CELL_MEDIATED_CYTOTOXICITY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION

GO Biological Process (28): negative regulation of T cell cytokine production (GO:0002725), intracellular iron ion homeostasis (GO:0006879), receptor-mediated endocytosis (GO:0006898), cell surface receptor signaling pathway (GO:0007166), response to iron ion (GO:0010039), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), BMP signaling pathway (GO:0030509), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), transferrin transport (GO:0033572), regulation of iron ion transport (GO:0034756), hormone biosynthetic process (GO:0042446), urate metabolic process (GO:0046415), positive regulation of receptor-mediated endocytosis (GO:0048260), positive regulation of SMAD protein signal transduction (GO:0060391), multicellular organismal-level iron ion homeostasis (GO:0060586), protein-containing complex assembly (GO:0065003), cellular response to iron ion (GO:0071281), positive regulation of peptide hormone secretion (GO:0090277), negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I (GO:1904283), response to iron ion starvation (GO:1990641), regulation of protein localization to cell surface (GO:2000008), negative regulation of ubiquitin-dependent protein catabolic process (GO:2000059), negative regulation of CD8-positive, alpha-beta T cell activation (GO:2001186), regulation of T cell mediated immunity (GO:0002709), monoatomic ion transport (GO:0006811), iron ion transport (GO:0006826), regulation of immune response (GO:0050776)

GO Molecular Function (6): signaling receptor binding (GO:0005102), beta-2-microglobulin binding (GO:0030881), co-receptor binding (GO:0039706), transporter activator activity (GO:0141109), transferrin receptor binding (GO:1990459), protein binding (GO:0005515)

GO Cellular Component (13): obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), early endosome (GO:0005769), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cytoplasmic vesicle (GO:0031410), apical part of cell (GO:0045177), basal part of cell (GO:0045178), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), HFE-transferrin receptor complex (GO:1990712), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Iron uptake and transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	3
inorganic ion homeostasis	2
iron ion transport	2
endosome	2
plasma membrane	2
cytoplasm	2
T cell cytokine production	1
negative regulation of T cell mediated immunity	1
negative regulation of cytokine production involved in immune response	1
regulation of T cell cytokine production	1
intracellular monoatomic cation homeostasis	1
endocytosis	1
signal transduction	1
response to metal ion	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
protein transport	1
regulation of metal ion transport	1
biosynthetic process	1
hormone metabolic process	1
small molecule metabolic process	1
purine-containing compound metabolic process	1
receptor-mediated endocytosis	1
positive regulation of endocytosis	1
regulation of receptor-mediated endocytosis	1
regulation of SMAD protein signal transduction	1
SMAD protein signal transduction	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of intracellular signal transduction	1
monoatomic cation homeostasis	1
multicellular organismal-level chemical homeostasis	1

Protein interactions and networks

STRING

1398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HFE	TFRC	P02786	999
HFE	TFR2	Q9UP52	999
HFE	HJV	Q6ZVN8	995
HFE	B2M	P01884	995
HFE	HAMP	P81172	965
HFE	TMPRSS6	Q8IU80	933
HFE	SLC40A1	Q9NP59	921
HFE	CYBRD1	Q53TN4	908
HFE	BMP6	P22004	905
HFE	SLC11A2	P49281	896
HFE	UROD	P06132	856
HFE	FTL	P02792	759
HFE	CP	P00450	727
HFE	ALAS2	P22557	693
HFE	ALB	P02768	679

IntAct

49 interactions, top by confidence:

A	B	Type	Score
HFE	B2M	psi-mi:“MI:0915”(physical association)	0.730
B2M	HFE	psi-mi:“MI:0915”(physical association)	0.730
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
B2M	NEMP1	psi-mi:“MI:0914”(association)	0.640
HFE	TFRC	psi-mi:“MI:0915”(physical association)	0.620
TFRC	HFE	psi-mi:“MI:0403”(colocalization)	0.620
CTSG	MANBA	psi-mi:“MI:0914”(association)	0.530
FUT1	NDUFS4	psi-mi:“MI:0914”(association)	0.530
HFE	ADAM10	psi-mi:“MI:0914”(association)	0.530
SMPDL3B	HFE	psi-mi:“MI:0915”(physical association)	0.400
rep	BMPR1B	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
HFE	PODXL	psi-mi:“MI:0914”(association)	0.350
APOM	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-C	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DPB1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DRB3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
P2RX2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ASIC4	TMEM131L	psi-mi:“MI:0914”(association)	0.350
B3GALT4		psi-mi:“MI:0914”(association)	0.350
PTPRN	KCNK1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
RLN1	MANBA	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (122): TFRC (Affinity Capture-Western), HFE (Affinity Capture-Western), HFE (Affinity Capture-MS), HFE (Affinity Capture-MS), HFE (Proximity Label-MS), ST6GALNAC4 (Affinity Capture-MS), ADAM22 (Affinity Capture-MS), TAF9B (Affinity Capture-MS), SUPT7L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), RAD21 (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K7V7, C1ITJ8, O08602, O08603, O08604, O19477, O35799, P01901, P01902, P06339, P13599, P14427, P14432, P16391, P25311, P26151, P30383, P55899, P60018, P70387, Q01965, Q29980, Q29983, Q2KN22, Q30201, Q3B8P2, Q5RD09, Q60I18, Q61559, Q63678, Q64726, Q6H3X3, Q8HWB0, Q8HWE5, Q8HWE7, Q8SPV9, Q8VD31, Q920A9, Q95460, Q9BCU3

Diamond homologs: A0A0G2K7V7, O19477, O35799, P01896, P01899, P01900, P01901, P10321, P13752, P15979, P16391, P30377, P30379, P30380, P30381, P30386, P30388, P30511, P30516, P60018, P70387, Q29980, Q29983, Q30201, Q60I18, Q8HWE5, Q8HWE7, Q9GKZ0, Q9GL41, Q9GL42, Q9GL43, C1ITJ8, P01888, P01889, P01893, P01894, P01895, P01897, P01898, P01902

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metabolism of carbohydrates and carbohydrate derivatives	6	19.5×	1e-04
Neutrophil degranulation	9	5.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

335 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	12
Uncertain significance	121
Likely benign	135
Benign	10

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071037	NM_000410.4(HFE):c.1022_1034del (p.His341fs)	Pathogenic
1072713	NM_000410.4(HFE):c.480del (p.Arg161fs)	Pathogenic
1454985	NM_000410.4(HFE):c.279del (p.Trp94fs)	Pathogenic
1456030	NM_000410.4(HFE):c.626del (p.Leu209fs)	Pathogenic
1458886	NM_000410.4(HFE):c.414C>G (p.Tyr138Ter)	Pathogenic
18	NM_000410.4(HFE):c.989G>T (p.Arg330Met)	Pathogenic
2016731	NM_000410.4(HFE):c.407G>A (p.Trp136Ter)	Pathogenic
2054741	NM_000410.4(HFE):c.616+1G>T	Pathogenic
2126877	NM_000410.4(HFE):c.760A>T (p.Lys254Ter)	Pathogenic
2199175	NM_000410.4(HFE):c.832C>T (p.Gln278Ter)	Pathogenic
2710835	NM_000410.4(HFE):c.663del (p.Thr222fs)	Pathogenic
2751130	NM_000410.4(HFE):c.840T>A (p.Tyr280Ter)	Pathogenic
2770771	NM_000410.4(HFE):c.720_726dup (p.Lys243delinsGluGlyTer)	Pathogenic
2803829	NM_000410.4(HFE):c.546C>A (p.Tyr182Ter)	Pathogenic
2837089	NM_000410.4(HFE):c.712A>T (p.Lys238Ter)	Pathogenic
2962260	NM_000410.4(HFE):c.610C>T (p.Gln204Ter)	Pathogenic
3017513	NM_000410.4(HFE):c.568C>T (p.Gln190Ter)	Pathogenic
3245973	NC_000006.11:g.(?26087669)(26094454_?)del	Pathogenic
3245974	NC_000006.11:g.(?26087669)(26091837_?)del	Pathogenic
3384778	NM_000410.4(HFE):c.166C>T (p.Gln56Ter)	Pathogenic
3613304	NM_000410.4(HFE):c.899C>A (p.Ser300Ter)	Pathogenic
3664385	NM_000410.4(HFE):c.774del (p.Asn259fs)	Pathogenic
3671897	NM_000410.4(HFE):c.440_446del (p.Glu147fs)	Pathogenic
3689840	NM_000410.4(HFE):c.693C>G (p.Tyr231Ter)	Pathogenic
4732018	NM_000410.4(HFE):c.1006+1G>T	Pathogenic
530393	NM_000410.4(HFE):c.762del (p.Asp255fs)	Pathogenic
88946	NM_000410.4(HFE):c.502G>T (p.Glu168Ter)	Pathogenic
1185560	NM_000410.4(HFE):c.262A>T (p.Ser88Cys)	Likely pathogenic
1217279	NM_000410.4(HFE):c.688TAC[1] (p.Tyr231del)	Likely pathogenic
1677541	NM_000410.4(HFE):c.340+1G>C	Likely pathogenic

SpliceAI

1291 predictions. Top by Δscore:

Variant	Effect	Δscore
6:26087515:GC:G	donor_gain	1.0000
6:26087517:G:GG	donor_gain	1.0000
6:26092682:AAGT:A	acceptor_gain	1.0000
6:26092683:A:G	acceptor_gain	1.0000
6:26092684:G:GG	acceptor_gain	1.0000
6:26092792:GA:G	donor_gain	1.0000
6:26092815:G:GT	donor_gain	1.0000
6:26092816:G:GT	donor_gain	1.0000
6:26092831:G:GT	donor_gain	1.0000
6:26092831:GAC:G	donor_gain	1.0000
6:26093117:A:AG	acceptor_gain	1.0000
6:26093118:G:GG	acceptor_gain	1.0000
6:26093216:G:GT	donor_gain	1.0000
6:26093233:G:GG	donor_gain	1.0000
6:26094281:G:GT	donor_gain	1.0000
6:26087512:GCTGC:G	donor_gain	0.9900
6:26091023:C:G	donor_gain	0.9900
6:26092678:T:A	acceptor_gain	0.9900
6:26092682:A:AG	acceptor_gain	0.9900
6:26092684:GT:G	acceptor_gain	0.9900
6:26092815:GGA:G	donor_gain	0.9900
6:26092834:G:GG	donor_gain	0.9900
6:26093118:GA:G	acceptor_gain	0.9900
6:26093118:GAGCC:G	acceptor_gain	0.9900
6:26093228:TTC:T	donor_gain	0.9900
6:26087514:TGC:T	donor_gain	0.9800
6:26087515:GCG:G	donor_gain	0.9800
6:26092684:GTGC:G	acceptor_gain	0.9800
6:26092793:A:G	donor_gain	0.9800
6:26092818:G:GG	donor_gain	0.9800

AlphaMissense

2276 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:26091438:G:C	W155C	0.993
6:26091438:G:T	W155C	0.993
6:26091480:G:C	W169C	0.990
6:26091480:G:T	W169C	0.990
6:26092783:T:A	W239R	0.990
6:26092783:T:C	W239R	0.990
6:26091056:T:C	F98L	0.989
6:26091058:C:A	F98L	0.989
6:26091058:C:G	F98L	0.989
6:26092785:G:C	W239C	0.989
6:26092785:G:T	W239C	0.989
6:26091416:T:C	F148S	0.988
6:26091436:T:A	W155R	0.988
6:26091436:T:C	W155R	0.988
6:26092741:T:A	C225S	0.988
6:26092742:G:C	C225S	0.988
6:26091343:T:A	C124S	0.986
6:26091344:G:C	C124S	0.986
6:26090903:T:C	F47L	0.984
6:26090905:T:A	F47L	0.984
6:26090905:T:G	F47L	0.984
6:26091046:G:C	W94C	0.983
6:26091046:G:T	W94C	0.983
6:26092912:T:A	C282S	0.982
6:26092913:G:C	C282S	0.982
6:26091326:T:C	L118P	0.981
6:26091415:T:C	F148L	0.980
6:26091417:C:A	F148L	0.980
6:26091417:C:G	F148L	0.980
6:26091044:T:A	W94R	0.979

dbSNP variants (sampled 300 via entrez): RS1000470656 (6:26095908 C>T), RS1000696519 (6:26089053 C>T), RS1000738662 (6:26095384 A>G), RS1001345852 (6:26097186 T>C), RS1001361619 (6:26086159 T>A), RS1001459567 (6:26088911 T>C), RS1001572476 (6:26089346 G>A), RS1002070106 (6:26096336 G>A), RS1002168538 (6:26092049 C>G), RS1003128351 (6:26090803 C>T), RS1003170474 (6:26093536 A>G), RS1003455301 (6:26093076 G>A), RS1003492652 (6:26086590 T>A,C), RS1003502151 (6:26097956 A>G), RS1003847309 (6:26097872 ACT>A)

Disease associations

OMIM: gene MIM:613609 | disease phenotypes: MIM:235200, MIM:176100, MIM:176200, MIM:219700, MIM:612635, MIM:104300

GenCC curated gene-disease

Disease	Classification	Inheritance
hemochromatosis type 1	Definitive	Autosomal recessive
cystic fibrosis	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hemochromatosis type 1	Definitive	AR

Mondo (16): Alzheimer disease (MONDO:0004975), cardiomyopathy (MONDO:0004994), hereditary hemochromatosis (MONDO:0006507), familial porphyria cutanea tarda (MONDO:0008296), variegate porphyria (MONDO:0008297), cystic fibrosis (MONDO:0009061), microvascular complications of diabetes, susceptibility to, 7 (MONDO:0012971), neuroendocrine neoplasm (MONDO:0019496), hemochromatosis type 1 (MONDO:0021001), Alzheimer disease type 1 (MONDO:0007088), hemochromatosis type 2 (MONDO:0019257), congenital nervous system disorder (MONDO:0002320), peripheral nervous system disorder (MONDO:0003620), peripheral neuropathy (MONDO:0005244), skin sensitivity to sun (MONDO:0005434)

Orphanet (13): Porphyria cutanea tarda (Orphanet:101330), Early-onset autosomal dominant Alzheimer disease (Orphanet:1020), Rare cardiomyopathy (Orphanet:167848), Rare hereditary hemochromatosis (Orphanet:220489), Familial porphyria cutanea tarda (Orphanet:443062), Symptomatic form of HFE-related hemochromatosis (Orphanet:465508), Cystic fibrosis (Orphanet:586), Variegate porphyria (Orphanet:79473), Neuroendocrine neoplasm (Orphanet:877), HJV or HAMP-related hemochromatosis (Orphanet:79230), Inherited cancer-predisposing syndrome (Orphanet:140162), NON RARE IN EUROPE: Alzheimer disease (Orphanet:238616), NON RARE IN EUROPE: Hemochromatosis type 1 (Orphanet:139498)

HPO phenotypes

86 total (30 of 86 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000029	Testicular atrophy
HP:0000044	Hypogonadotropic hypogonadism
HP:0000141	Amenorrhea
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000771	Gynecomastia
HP:0000787	Nephrolithiasis
HP:0000789	Infertility
HP:0000802	Impotence
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000953	Hyperpigmentation of the skin
HP:0001009	Telangiectasia
HP:0001254	Lethargy
HP:0001324	Muscle weakness
HP:0001369	Arthritis
HP:0001386	Joint swelling
HP:0001387	Joint stiffness
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001402	Hepatocellular carcinoma
HP:0001409	Portal hypertension
HP:0001508	Failure to thrive

GWAS associations

149 associations (top):

Study	Trait	p-value
GCST000301_22	Iron status biomarkers	4.000000e-11
GCST000301_3	Iron status biomarkers	1.000000e-10
GCST000301_7	Iron status biomarkers	4.000000e-15
GCST000498_3	Hematological parameters	1.000000e-23
GCST000499_2	Hemoglobin	6.000000e-19
GCST000501_1	Hemoglobin	1.000000e-08
GCST000502_8	Hematocrit	2.000000e-09
GCST000503_1	Mean corpuscular volume	1.000000e-46
GCST000505_1	Iron status biomarkers	5.000000e-07
GCST000505_4	Iron status biomarkers	2.000000e-08
GCST000585_16	Mean corpuscular volume	2.000000e-06
GCST000759_6	LDL cholesterol	6.000000e-10
GCST000760_30	Cholesterol, total	2.000000e-08
GCST000803_9	Glycated hemoglobin levels	3.000000e-20
GCST000814_2	Red blood cell traits	6.000000e-07
GCST000814_3	Red blood cell traits	3.000000e-09
GCST000913_3	Iron status biomarkers	9.000000e-09
GCST000913_5	Iron status biomarkers	9.000000e-10
GCST000935_5	Iron status biomarkers	3.000000e-09
GCST001021_5	Iron status biomarkers	3.000000e-08
GCST001021_6	Iron status biomarkers	6.000000e-10
GCST001103_5	Alcohol consumption (transferrin glycosylation)	2.000000e-32
GCST001174_2	Hepcidin levels	4.000000e-09
GCST001174_3	Hepcidin levels	5.000000e-11
GCST001174_4	Hepcidin levels	3.000000e-07
GCST001174_6	Hepcidin levels	3.000000e-15
GCST001227_3	Systolic blood pressure	8.000000e-12
GCST001228_11	Diastolic blood pressure	2.000000e-15
GCST001236_4	Blood pressure	2.000000e-12
GCST001238_7	Hypertension	2.000000e-10

EFO canonical traits (36, from GWAS)

EFO ID	Trait name
EFO:0004461	iron biomarker measurement
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004541	HbA1c measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004460	soluble transferrin receptor measurement
EFO:0004459	ferritin measurement
EFO:0006334	total iron binding capacity
EFO:0004329	alcohol drinking
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0006341	transferrin measurement
EFO:0006333	transferrin saturation measurement
EFO:0007901	hepcidin:ferritin ratio
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0007986	reticulocyte count
EFO:0004337	intelligence
EFO:0006527	smoking status measurement
EFO:0009188	Red cell distribution width
EFO:0009595	guilt measurement
EFO:0009589	worry measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0008111	diet measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D000544	Alzheimer Disease	C10.228.140.380.100; C10.574.945.249; F03.615.400.100
D009202	Cardiomyopathies	C14.280.238
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213
D006432	Hemochromatosis	C16.320.565.618.337; C18.452.565.500.480; C18.452.648.618.337
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D018358	Neuroendocrine Tumors	C04.557.465.625.650; C04.557.580.625.650
D010523	Peripheral Nervous System Diseases	C10.668.829
D046350	Porphyria, Variegate	C06.552.830.625; C16.320.850.742.625; C17.800.827.742.625; C18.452.811.400.625
C536594	Alzheimer disease type 1 (supp.)
C537247	Hemochromatosis, type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2071303	Efficacy	3	adalimumab	Crohn Disease

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1799945	HFE		0.00	0
rs1800562	HFE		0.00	0
rs2071303	HFE	3	2.75	1	adalimumab
rs2858996	HFE		0.00	0

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Iron	affects abundance, decreases uptake, decreases reaction, increases reaction, increases abundance (+3 more)	9
Air Pollutants	decreases expression, increases abundance, affects response to substance	3
Lead	affects response to substance, increases response to substance	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
sodium arsenite	decreases expression, increases expression	2
Vehicle Emissions	affects response to substance, increases expression	2
Paraquat	decreases response to substance, affects reaction, decreases expression, affects response to substance	2
Valproic Acid	affects cotreatment, increases expression, affects expression	2
Cadmium Chloride	decreases expression, increases expression	2
Asian ginseng	decreases expression, decreases reaction, affects cotreatment, increases expression	1
ginger extract	decreases expression, increases abundance	1
bufotalin	decreases expression	1
propionaldehyde	decreases expression	1
cinnamaldehyde	increases expression	1
beta-lapachone	decreases expression	1
zinc protoporphyrin	affects abundance	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
ceric oxide	decreases expression	1
hydroquinone	decreases expression	1
cobalt oxide	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases response to substance	1
Acetaminophen	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1

Cellosaurus cell lines

39 cell lines: 33 transformed cell line, 5 cancer cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_4W10	GM16028	Transformed cell line	Female
CVCL_5A96	GM14620	Transformed cell line	Male
CVCL_5A97	GM14621	Transformed cell line	Male
CVCL_5A99	GM14631	Transformed cell line	Female
CVCL_5B00	GM14640	Transformed cell line	Male
CVCL_5B01	GM14650	Transformed cell line	Female
CVCL_5B02	GM14651	Transformed cell line	Male
CVCL_5B03	GM14652	Transformed cell line	Male
CVCL_5B04	GM14657	Transformed cell line	Female
CVCL_5B05	GM14685	Transformed cell line	Male

Clinical trials (associated diseases)

600 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	PHASE4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	PHASE4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	PHASE4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	PHASE4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	PHASE4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	PHASE4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	PHASE4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	PHASE4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	PHASE4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	PHASE4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	PHASE4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	PHASE4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	PHASE4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	PHASE4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	PHASE4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	PHASE4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	PHASE4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	PHASE4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	PHASE4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	PHASE4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	PHASE4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	PHASE4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	PHASE4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	PHASE4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	PHASE4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	PHASE4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	PHASE4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	PHASE4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	PHASE4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	PHASE4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	PHASE4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	PHASE4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	PHASE4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis