SERPINA1

Summary

SERPINA1 (serpin family A member 1, HGNC:8941) is a protein-coding gene on chromosome 14q32.13, encoding Alpha-1-antitrypsin (P01009). Inhibitor of serine proteases.

The protein encoded by this gene is a serine protease inhibitor belonging to the serpin superfamily whose targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. This protein is produced in the liver, the bone marrow, by lymphocytic and monocytic cells in lymphoid tissue, and by the Paneth cells of the gut. Defects in this gene are associated with chronic obstructive pulmonary disease, emphysema, and chronic liver disease. Several transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 5265 — RefSeq curated summary.

At a glance

• Gene–disease (curated): alpha 1-antitrypsin deficiency (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 56
• Clinical variants (ClinVar): 528 total — 34 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 62
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000295

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8941
Approved symbol	SERPINA1
Name	serpin family A member 1
Location	14q32.13
Locus type	gene with protein product
Status	Approved
Aliases	AAT, A1A, PI1, alpha-1-antitrypsin, A1AT, alpha1AT
Ensembl gene	ENSG00000197249
Ensembl biotype	protein_coding
OMIM	107400
Entrez	5265

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 52 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000355814, ENST00000393087, ENST00000393088, ENST00000402629, ENST00000404814, ENST00000437397, ENST00000440909, ENST00000448921, ENST00000449399, ENST00000489769, ENST00000553327, ENST00000554720, ENST00000555289, ENST00000556091, ENST00000556955, ENST00000557093, ENST00000557118, ENST00000557361, ENST00000557492, ENST00000636712, ENST00000866514, ENST00000866515, ENST00000866516, ENST00000866517, ENST00000866518, ENST00000866519, ENST00000866520, ENST00000866521, ENST00000866522, ENST00000866523, ENST00000866524, ENST00000866525, ENST00000866526, ENST00000866527, ENST00000866528, ENST00000866529, ENST00000866530, ENST00000866531, ENST00000866532, ENST00000866533, ENST00000866534, ENST00000866535, ENST00000866536, ENST00000866537, ENST00000866538, ENST00000866539, ENST00000866540, ENST00000866541, ENST00000866542, ENST00000959498, ENST00000959499, ENST00000959500, ENST00000959501, ENST00000959502, ENST00000959503, ENST00000959504

RefSeq mRNA: 11 — MANE Select: NM_000295 NM_000295, NM_001002235, NM_001002236, NM_001127700, NM_001127701, NM_001127702, NM_001127703, NM_001127704, NM_001127705, NM_001127706, NM_001127707

CCDS: CCDS9925

Canonical transcript exons

ENST00000393087 — 5 exons

Exon	Start	End
ENSE00001302079	94382592	94383241
ENSE00001310159	94380871	94381141
ENSE00001354435	94376747	94378640
ENSE00001514156	94388560	94388602
ENSE00003651351	94379464	94379611

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 746.7965 / max 304631.1921, expressed in 1036 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144731	661.9594	493
144733	47.8722	709
144735	18.8744	664
144734	6.2083	563
144727	3.2093	207
144729	1.8457	156
144732	1.5835	287
144703	1.2585	83
144728	0.8627	113
144720	0.4663	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.96	gold quality
liver	UBERON:0002107	99.95	gold quality
blood	UBERON:0000178	99.73	gold quality
islet of Langerhans	UBERON:0000006	99.71	gold quality
monocyte	CL:0000576	99.67	gold quality
leukocyte	CL:0000738	99.67	gold quality
granulocyte	CL:0000094	99.60	gold quality
gall bladder	UBERON:0002110	99.43	gold quality
duodenum	UBERON:0002114	99.23	gold quality
adult mammalian kidney	UBERON:0000082	99.18	gold quality
upper lobe of left lung	UBERON:0008952	99.15	gold quality
metanephros cortex	UBERON:0010533	99.08	gold quality
vermiform appendix	UBERON:0001154	99.03	gold quality
right lung	UBERON:0002167	98.94	gold quality
spleen	UBERON:0002106	98.83	gold quality
pancreas	UBERON:0001264	97.60	gold quality
body of pancreas	UBERON:0001150	96.86	gold quality
kidney	UBERON:0002113	96.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.58	gold quality
lung	UBERON:0002048	96.34	gold quality
small intestine	UBERON:0002108	96.28	gold quality
rectum	UBERON:0001052	96.27	gold quality
bone marrow	UBERON:0002371	96.24	gold quality
bone marrow cell	CL:0002092	95.11	gold quality
mucosa of transverse colon	UBERON:0004991	94.66	gold quality
cortex of kidney	UBERON:0001225	94.16	gold quality
body of stomach	UBERON:0001161	92.58	gold quality
stomach	UBERON:0000945	92.35	gold quality
lymph node	UBERON:0000029	92.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.29	silver quality

Single-cell (SCXA)

Detected in 39 experiment(s), a significant marker in 34.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	18536.16
E-MTAB-7407	yes	13751.36
E-HCAD-9	yes	12646.45
E-MTAB-8495	yes	4410.73
E-MTAB-9906	yes	4163.03
E-GEOD-125970	yes	3083.40
E-HCAD-31	yes	2715.97
E-ENAD-27	yes	2298.01
E-GEOD-81608	yes	1896.01
E-GEOD-86618	yes	1667.05
E-MTAB-10485	yes	1527.20
E-MTAB-6678	yes	1482.88
E-HCAD-38	yes	1441.30
E-MTAB-8498	yes	1391.90
E-GEOD-149689	yes	1035.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, FOXM1, HNF1A, HNF1B, HNF4A, HNF4G, KLF6, NFE2L2, NKRF, ONECUT1, SP1, TBX15, TCF3

miRNA regulators (miRDB)

72 targeting SERPINA1, 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-6798-5P	100.00	65.77	699
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4269	99.55	69.89	1373

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Results show that nephropathy is not a direct and single expression of alpha-1-antitrypsin deficiency. (PMID:11744816)
• have used reactive loop peptides to explore the differences between the pathogenic Z and normal M alpha(1)-antitrypsin (PMID:11773044)
• Concerted regulation of inhibitory activity of alpha 1-antitrypsin by the native strain distributed throughout the molecule. (PMID:11834734)
• In vitro formation of triple-stranded dna structures in the human alpha1-Antitrypsin gene (alpha1-antitrypsin) (PMID:11862702)
• induction of expression by oncostatin M mediated by a 3’ enhancer (PMID:11936950)
• reactivity and oxidation pathway of cysteine 232 residue (PMID:11991955)
• The oxidation kinetics of each of alpha 1-antitrypsin’s methionines has been reported for recombinant alpha 1-AT(C232S) as well as for M351L and M358V mutants, with new insights into the protein’s solution structure. (PMID:12009885)
• alpha1-antitrypsin deficiency and dementia (PMID:12023831)
• Gene regulation of the serine proteinase inhibitors alpha1-antitrypsin and alpha1-antichymotrypsin. (PMID:12023832)
• identified as a protective factor in plasma that neutralizes neutrophil degradation of scu-PA, tcu-PA, t-PA and plasmin (PMID:12083479)
• a protein identical to or highly homologous with serum A1AT was purified from follicular fluid; follicular fluid A1AT did not show a stimulatory effect on sperm motility (PMID:12223217)
• alpha(1)-antitrypsin and antichymotrypsin are produced by the mammary gland and are present in milk in relatively high amounts in early lactation (PMID:12324297)
• the alpha 1 antitrypsin polymorphisms, especially Pi*Z, could help to predict asbestosis risk (PMID:12368052)
• Acid denaturation of alpha1-antitrypsin: characterization of a novel mechanism of serpin polymerization. (PMID:12460583)
• deficiency involved in liver and mitochondrial injury (REVIEW) (PMID:12464659)
• Alpha1-antitrypsin polymerization and the serpinopathies(REVIEW) (PMID:12464660)
• Data identify residues in alpha(1)-antitrypsin that appear to play a key role in inducing or preventing conformational change. (PMID:12498804)
• examination of novel mode of polymerization (PMID:12649292)
• In the proposed stochastic model, the delayed onset of the glycan modification, relative to the duration of nonnative protein structure, coordinates preferential degradation of misfolded alpha 1-anatitrypsin monomer & spares the native molecule. (PMID:12815101)
• First comprehensive analysis of the genetic diversity of the AAT gene in a cohort from sub-Saharan Africa. (PMID:12815594)
• alpha 1 antitrypsin simultaneously and differently inhibits processing of HIV-1 Env and Gag, intracellularly, at least in part, by blocking cellular furin. (PMID:12878320)
• Low plasma levels of A1AT may be a risk factor for spontaneous cervical artery dissections (PMID:12893950)
• Alpha1PI promotes copatching of human leukocyte elastase with canonical HIV receptors. HLE & its ligand alpha1PI can serve as HIV coreceptor and cofactor & potentially participate in the pathophysiology of HIV disease progression. (PMID:12933574)
• in community acquired pneumonia, both A1AT and SLPI were cleaved or complexed in infected lobes and A1AT was oxidized; conclude that mean elastase levels are increased and that mean anti-elastase capacity is decreased in pneumonic lobes (PMID:12934194)
• A new M-like-null variant of alpha-1-antitrypsin associated with panacinar emphysema was found in a 73 year-old woman non-smoker. (PMID:14639110)
• alpha1-antitrypsin has a role in neutrophil activation (PMID:14766206)
• HSP70 and alpha1AT have immunogenic roles in diabetes mellitus (PMID:14766207)
• No correlation between alpha-1-antitrypsin phenotype and lung, prostate, or breast cancer in Jordan (PMID:14968215)
• A model cell system of endoplasmic reticulum (ER) stress signals induced by variant Z alpha 1-antitrypsin (A1AT) demonstrates that both ER overload response and unfolded protein response are activated by the variant Z A1AT, but not wild-type A1AT. (PMID:15100318)
• identified as a new binding partner for E.coli EspB and EspD, suggesting a previously unappreciated role for AAT in host cell defense against enteropathogenic Escherichia coli infections and potentially also against other bacterial pathogens. (PMID:15271889)
• C26, the C-terminal 26 residue peptide of serpin A1, significantly increased cell proliferation in cultures of hepatoma cells. (PMID:15498560)
• screening the exonic regions, 5’ and 3’ flanking sequence of the AAT gene in order to generate a high density map of single nucleotide polymorphisms (SNPs) (PMID:15532029)
• This review characterizes the unique physiological properties of alpha 1-antitrypsin (AAT) and its role as a diagnostic tool in lung and liver disorders associated with AAT serum deficiency. (PMID:15653097)
• serpin/furin complex stability depends on pH and regulation at the deacylation step (PMID:15659365)
• Thirteen individuals showed biallelic expression of PI gene, and three individuals showed monoallelic expression. (PMID:15674733)
• polymeric alpha(1)-anti-trypsin co-localizes with neutrophils in the alveoli of individuals with Z alpha(1)-antitrypsin-related emphysema (PMID:15681822)
• Polymerizing alpha 1-antitrypsin study clearly shows existence of a kinetic lag phase during which short oligomers are formed prior to the formation of heterogeneous mixtures of longer polymers produced via condensation of shorter oligomers. (PMID:15709777)
• The results revealed that the frequency of M1S, M2S, M1Z, and MV alpha 1-antitrypsin phenotypes were significantly higher in uveitis patients (PMID:15820772)
• The PIM3 allele of the alpha1AT gene is found to have an association with the pathogenesis of COPD in the Indian population. (PMID:15820782)
• We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects. (PMID:15927063)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serpina1a	ENSMUSG00000066366
mus_musculus	Serpina1d	ENSMUSG00000071177
mus_musculus	Serpina1b	ENSMUSG00000071178
mus_musculus	Serpina1e	ENSMUSG00000072849
mus_musculus	Serpina1c	ENSMUSG00000079015
rattus_norvegicus	Serpina1	ENSRNOG00000032669

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINI2 (ENSG00000114204), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINB6 (ENSG00000124570), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), SERPINE2 (ENSG00000135919), SERPINA10 (ENSG00000140093), SERPING1 (ENSG00000149131), SERPINH1 (ENSG00000149257), SERPINI1 (ENSG00000163536), SERPINA12 (ENSG00000165953), SERPINB7 (ENSG00000166396), SERPINB8 (ENSG00000166401), SERPINB12 (ENSG00000166634), SERPINF2 (ENSG00000167711), SERPINA9 (ENSG00000170054), SERPINA6 (ENSG00000170099), SERPINB9 (ENSG00000170542), SERPINA11 (ENSG00000186910), SERPINA5 (ENSG00000188488), SERPINA3 (ENSG00000196136), SERPINB2 (ENSG00000197632), SERPINB13 (ENSG00000197641), SERPINB11 (ENSG00000206072), SERPINB4 (ENSG00000206073), SERPINB5 (ENSG00000206075), HMSD (ENSG00000221887), SERPINB10 (ENSG00000242550), SERPINE3 (ENSG00000253309), SERPINA2 (ENSG00000258597)

Protein

Protein identifiers

Alpha-1-antitrypsin — P01009 (reviewed: P01009)

Alternative names: Alpha-1 protease inhibitor, Alpha-1-antiproteinase, Serpin A1

All UniProt accessions (8): A0A0B4J278, E9KL23, P01009, G3V2B9, G3V387, G3V4I7, G3V544, G3V5R8

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin. Reversible chymotrypsin inhibitor. It also inhibits elastase, but not trypsin. Its major physiological function is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE).

Subunit / interactions. Interacts with CELA2A. Interacts with ERGIC3 and LMAN1/ERGIC53. Interacts with PRSS1/trypsin. Interacts with PRSS1/Trypsin. The variants S and Z interact with CANX and PDIA3.

Subcellular location. Secreted. Endoplasmic reticulum Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Ubiquitous. Expressed in leukocytes and plasma.

Post-translational modifications. N-glycosylated. Differential glycosylation produces a number of isoforms. N-linked glycan at Asn-107 is alternatively di-antennary, tri-antennary or tetra-antennary. The glycan at Asn-70 is di-antennary with trace amounts of tri-antennary. Glycan at Asn-271 is exclusively di-antennary. Structure of glycans at Asn-70 and Asn-271 is Hex5HexNAc4. The structure of the antennae is Neu5Ac(alpha1-6)Gal(beta1-4)GlcNAc attached to the core structure Man(alpha1-6)[Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc. Some antennae are fucosylated, which forms a Lewis-X determinant. Proteolytic processing may yield the truncated form that ranges from Asp-30 to Lys-418. (Microbial infection) Proteolytically processed by Staphylococcus aureus seryl, cysteinyl, and metallo-proteases.

Disease relevance. Alpha-1-antitrypsin deficiency (A1ATD) [MIM:613490] An autosomal recessive disorder characterized by serum levels of alpha-1-antitrypsin below the normal range, and an increased risk for developing pulmonary emphysema and, to a lesser extent, chronic liver disease. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.

Polymorphism. The sequence shown is that of the M1V allele which is the most common form of PI (44 to 49%). Other frequent alleles are: M1A 20 to 23%; M2 10 to 11%; M3 14 to 19%.

Miscellaneous. The aberrant form is found in the plasma of chronic smokers, and persists after smoking is ceased. It can still be found ten years after smoking has ceased. 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 serpin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P01009-1	1	yes
P01009-2	2
P01009-3	3

RefSeq proteins (11): NP_000286, NP_001002235, NP_001002236, NP_001121172, NP_001121173, NP_001121174, NP_001121175, NP_001121176, NP_001121177, NP_001121178, NP_001121179 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023795	Serpin_CS	Conserved_site
IPR023796	Serpin_dom	Domain
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily
IPR042185	Serpin_sf_2	Homologous_superfamily

Pfam: PF00079

UniProt features (111 total): sequence variant 38, strand 22, sequence conflict 14, helix 13, turn 8, glycosylation site 3, site 3, modified residue 3, splice variant 2, signal peptide 1, chain 1, peptide 1, region of interest 1, mutagenesis site 1

Structure

Experimental structures (PDB)

46 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8PI2	X-RAY DIFFRACTION	1.48
3NDD	X-RAY DIFFRACTION	1.5
6I7U	X-RAY DIFFRACTION	1.55
5NBU	X-RAY DIFFRACTION	1.67
8QZ5	X-RAY DIFFRACTION	1.69
5NBV	X-RAY DIFFRACTION	1.73
7AEL	X-RAY DIFFRACTION	1.76
6I4V	X-RAY DIFFRACTION	1.78
3NE4	X-RAY DIFFRACTION	1.81
7NPL	X-RAY DIFFRACTION	1.82
7NPK	X-RAY DIFFRACTION	1.83
9GGP	X-RAY DIFFRACTION	1.84
6ROD	X-RAY DIFFRACTION	1.85
6IAY	X-RAY DIFFRACTION	1.9
4PYW	X-RAY DIFFRACTION	1.91
8P4J	X-RAY DIFFRACTION	1.91
8R13	X-RAY DIFFRACTION	1.95
1QLP	X-RAY DIFFRACTION	2
2QUG	X-RAY DIFFRACTION	2
1HP7	X-RAY DIFFRACTION	2.1
1IZ2	X-RAY DIFFRACTION	2.2
3DRM	X-RAY DIFFRACTION	2.2
1OPH	X-RAY DIFFRACTION	2.3
8P4U	X-RAY DIFFRACTION	2.4
9HUD	X-RAY DIFFRACTION	2.42
3CWL	X-RAY DIFFRACTION	2.44
3CWM	X-RAY DIFFRACTION	2.51
1EZX	X-RAY DIFFRACTION	2.6
1QMB	X-RAY DIFFRACTION	2.6
9VDI	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01009-F1	89.14	0.79

Antibody-complex structures (SAbDab): 3 — 6HX4, 6I3Z, 9GGP

Functional residue map

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

Catalytic / active sites (3): 352–353 ((microbial infection) cleavage; by staphylococcus aureus aureolysin/aur); 354–355 ((microbial infection) cleavage; by staphylococcus aureus serine and cysteine proteinases); 382–383 (reactive bond)

Post-translational modifications (3): 38, 256, 383

Glycosylation sites (3): 70, 107, 271

Mutagenesis-validated functional residues (1):

Position	Phenotype
382	oxidation-resistant inhibitor of therapeutic importance.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-5694530	Cargo concentration in the ER
R-HSA-6798695	Neutrophil degranulation
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-109582	Hemostasis
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+
R-HSA-948021	Transport to the Golgi and subsequent modification

MSigDB gene sets: 446 (showing top): MODULE_52, REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, MODULE_45, GOZGIT_ESR1_TARGETS_DN, REACTOME_MEMBRANE_TRAFFICKING, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, MODULE_66, GOBP_WOUND_HEALING, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, KOYAMA_SEMA3B_TARGETS_UP, GOCC_COATED_VESICLE

GO Biological Process (3): acute-phase response (GO:0006953), blood coagulation (GO:0007596), hemostasis (GO:0007599)

GO Molecular Function (5): protease binding (GO:0002020), serine-type endopeptidase inhibitor activity (GO:0004867), identical protein binding (GO:0042802), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (11): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), COPII-coated ER to Golgi transport vesicle (GO:0030134), extracellular matrix (GO:0031012), platelet alpha granule lumen (GO:0031093), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	2
Metabolism of proteins	2
Post-translational protein modification	2
Response to elevated platelet cytosolic Ca2+	1
Innate Immune System	1
Immune System	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Hemostasis	1
Platelet activation, signaling and aggregation	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
intracellular organelle lumen	2
acute inflammatory response	1
hemostasis	1
wound healing	1
coagulation	1
regulation of body fluid levels	1
enzyme binding	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
protein binding	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1
endoplasmic reticulum	1
coated vesicle	1
external encapsulating structure	1
platelet alpha granule	1
secretory granule lumen	1
endoplasmic reticulum-Golgi intermediate compartment	1
bounding membrane of organelle	1
extracellular vesicle	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

3298 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINA1	ELANE	P08246	999
SERPINA1	ALB	P02768	996
SERPINA1	A2M	P01023	977
SERPINA1	PRSS2	P07478	977
SERPINA1	CTRB2	Q6GPI1	958
SERPINA1	CTRB1	P17538	957
SERPINA1	TTR	P02766	954
SERPINA1	ORM1	P02763	950
SERPINA1	ORM2	P19652	949
SERPINA1	CP	P00450	923
SERPINA1	HP	P00737	919
SERPINA1	AHSG	P02765	913
SERPINA1	AFP	P02771	907
SERPINA1	APOA1	P02647	893
SERPINA1	KNG1	P01042	889

IntAct

136 interactions, top by confidence:

A	B	Type	Score
SERPINA1	SERPINA1	psi-mi:“MI:0407”(direct interaction)	0.840
MAPK6	HERC2	psi-mi:“MI:0914”(association)	0.840
SERPINA1	PRSS1	psi-mi:“MI:0915”(physical association)	0.820
PRSS1	SERPINA1	psi-mi:“MI:0407”(direct interaction)	0.820
PRSS1	SERPINA1	psi-mi:“MI:0194”(cleavage reaction)	0.820
SERPINA1	PRSS1	psi-mi:“MI:0407”(direct interaction)	0.820
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CCNA2	GMNN	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
SERPINA1	ELANE	psi-mi:“MI:0407”(direct interaction)	0.590
MAGEB6	SERPINA1	psi-mi:“MI:0915”(physical association)	0.560
SERPINA1	TMPRSS2	psi-mi:“MI:0194”(cleavage reaction)	0.560
TMPRSS2	SERPINA1	psi-mi:“MI:0194”(cleavage reaction)	0.560
SERPINA1	CELA1	psi-mi:“MI:0407”(direct interaction)	0.560
CELA1	SERPINA1	psi-mi:“MI:0407”(direct interaction)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
CA8	IGLL5	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
ICE2	HP	psi-mi:“MI:0914”(association)	0.530
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530

BioGRID (183): SERPINA1 (Two-hybrid), SERPINA1 (Affinity Capture-MS), SERPINA1 (Affinity Capture-MS), SERPINA1 (Affinity Capture-MS), SERPINA1 (Affinity Capture-MS), SERPINA1 (Affinity Capture-MS), SERPINA1 (Affinity Capture-MS), SERPINA1 (Affinity Capture-MS), SERPINA1 (Synthetic Growth Defect), SERPINA1 (Affinity Capture-Western), SERPINA1 (Affinity Capture-Western), SERPINA1 (Affinity Capture-Western), SERPINA1 (Affinity Capture-Western), SYVN1 (Affinity Capture-Western), SQSTM1 (Affinity Capture-Western)

ESM2 similar proteins: A2I7M9, A2I7N0, A2I7N1, A2I7N2, A2I7N3, A6QPQ2, B2D1U1, E1BF81, O54762, P01009, P01011, P05154, P05544, P05545, P07758, P07759, P08185, P09006, P20848, P22323, P22324, P22325, P22599, P26595, P29621, P29622, P49920, P50451, P70458, Q00896, Q00897, Q00898, Q03734, Q3ZEJ6, Q5I2A0, Q5R536, Q5R9E3, Q5RCR2, Q5RCW5, Q60396

Diamond homologs: A2I7M9, A2I7N0, A2I7N1, A2I7N2, A2I7N3, A6QPQ2, B2D1U1, E1BF81, O00394, O54757, O54758, O54759, O54760, O54761, O54762, O54763, O75830, P01009, P01010, P01011, P05154, P05543, P05544, P05545, P05619, P07758, P07759, P08185, P09005, P09006, P12725, P17475, P20848, P22323, P22324, P22325, P22599, P23035, P23775, P26595

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
LMAN2	“up-regulates quantity by stabilization”	SERPINA1	binding
SERPINA1	“down-regulates activity”	F12	binding
SERPINA1	“down-regulates activity”	F2	binding
SERPINA1	up-regulates	LRP1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	28
Uncertain significance	136
Likely benign	217
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074773	NM_000295.5(SERPINA1):c.607_608del (p.Asp203fs)	Pathogenic
1075108	NM_000295.5(SERPINA1):c.1113_1114del (p.Ala372fs)	Pathogenic
1454847	NC_000014.8:g.(?94843455)(94854896_?)del	Pathogenic
1457397	NC_000014.8:g.(?94843455)(94847488_?)del	Pathogenic
1457874	NM_000295.5(SERPINA1):c.1052del (p.Leu351fs)	Pathogenic
1459806	NC_000014.8:g.(?94847198)(94854896_?)del	Pathogenic
1460301	NM_000295.5(SERPINA1):c.787del (p.Val263fs)	Pathogenic
17965	NM_001127701.1(SERPINA1):c.1178C>T (p.Pro393Leu)	Pathogenic
17976	NM_000295.5(SERPINA1):c.552del (p.Asp183_Tyr184insTer)	Pathogenic
17977	NM_000295.4(SERPINA1):c.721A>T (p.Lys241Ter)	Pathogenic
17982	NM_001127701.1(SERPINA1):c.1145T>G (p.Met382Arg)	Pathogenic
188845	NM_000295.5(SERPINA1):c.1158dup (p.Glu387fs)	Pathogenic
1997864	NM_000295.5(SERPINA1):c.403C>T (p.Gln135Ter)	Pathogenic
2060342	NM_000295.5(SERPINA1):c.847A>T (p.Lys283Ter)	Pathogenic
2174665	NM_000295.5(SERPINA1):c.853C>T (p.Gln285Ter)	Pathogenic
217816	QOgranite falls allele	Pathogenic
219364	NM_000295.5(SERPINA1):c.538C>T (p.Gln180Ter)	Pathogenic
2690996	NM_000295.5(SERPINA1):c.568C>T (p.Gln190Ter)	Pathogenic
2968675	NM_000295.5(SERPINA1):c.343C>T (p.Gln115Ter)	Pathogenic
315028	NM_000295.5(SERPINA1):c.221TCT[2] (p.Phe76del)	Pathogenic
3683122	NM_000295.5(SERPINA1):c.1135del (p.Ala379fs)	Pathogenic
370034	NM_000295.5(SERPINA1):c.288_291del (p.His97fs)	Pathogenic
3704457	NM_000295.5(SERPINA1):c.917+1G>A	Pathogenic
4085391	NM_000295.5(SERPINA1):c.613_614dup (p.Ala207fs)	Pathogenic
4281636	NM_000295.5(SERPINA1):c.979dup (p.Leu327fs)	Pathogenic
444034	NM_000295.5(SERPINA1):c.1064_1066-3del (p.Lys355_Ala356=)	Pathogenic
444035	NM_000295.5(SERPINA1):c.1072_1073del (p.Val357_His358insTer)	Pathogenic
444039	NM_000295.5(SERPINA1):c.1del (p.Met1fs)	Pathogenic
444040	NM_000295.5(SERPINA1):c.227T>C (p.Phe76Ser)	Pathogenic
4752007	NM_000295.5(SERPINA1):c.-5+1G>C	Pathogenic

SpliceAI

978 predictions. Top by Δscore:

Variant	Effect	Δscore
14:94378637:CGGC:C	acceptor_gain	1.0000
14:94378641:C:CC	acceptor_gain	1.0000
14:94378642:T:A	acceptor_loss	1.0000
14:94379459:CTCA:C	donor_loss	1.0000
14:94379461:CA:C	donor_loss	1.0000
14:94379462:A:AG	donor_loss	1.0000
14:94379463:C:A	donor_loss	1.0000
14:94379575:A:T	acceptor_gain	1.0000
14:94379607:CAGAC:C	acceptor_gain	1.0000
14:94379610:ACCTG:A	acceptor_loss	1.0000
14:94379611:CCT:C	acceptor_loss	1.0000
14:94379612:C:CA	acceptor_loss	1.0000
14:94379612:C:CC	acceptor_gain	1.0000
14:94379616:CG:C	acceptor_gain	1.0000
14:94379617:G:C	acceptor_gain	1.0000
14:94381142:C:CC	acceptor_gain	1.0000
14:94382589:TA:T	donor_loss	1.0000
14:94390460:T:A	donor_gain	1.0000
14:94378639:GC:G	acceptor_gain	0.9900
14:94378640:CC:C	acceptor_gain	0.9900
14:94379462:A:AC	donor_gain	0.9900
14:94379463:C:CC	donor_gain	0.9900
14:94379574:C:CT	acceptor_gain	0.9900
14:94379609:GAC:G	acceptor_gain	0.9900
14:94379617:G:GC	acceptor_gain	0.9900
14:94379620:C:CT	acceptor_gain	0.9900
14:94379621:A:T	acceptor_gain	0.9900
14:94380782:AGC:A	donor_gain	0.9900
14:94380845:TGGTC:T	donor_gain	0.9900
14:94380868:CACC:C	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000155541 (14:94390119 C>T), RS1000546000 (14:94386357 G>A), RS1000617320 (14:94389521 C>T), RS1000702667 (14:94389347 G>C), RS1000731202 (14:94384345 T>C), RS1000807089 (14:94385420 C>T), RS1001489458 (14:94384918 A>T), RS1001626880 (14:94385528 C>T), RS1001844538 (14:94377868 G>A,T), RS1002375690 (14:94388343 A>C), RS1002401962 (14:94389191 T>C), RS1002604211 (14:94391687 C>T), RS1002731664 (14:94381747 G>A,T), RS1003331632 (14:94388255 C>T), RS1003379161 (14:94390409 G>C)

Disease associations

OMIM: gene MIM:107400 | disease phenotypes: MIM:613490, MIM:606963, MIM:309548, MIM:219700, MIM:618242

GenCC curated gene-disease

Disease	Classification	Inheritance
alpha 1-antitrypsin deficiency	Strong	Autosomal recessive
hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation	Supportive	Autosomal dominant
cystic fibrosis	Supportive	Autosomal recessive

Mondo (9): alpha 1-antitrypsin deficiency (MONDO:0013282), chronic obstructive pulmonary disease (MONDO:0005002), FRAXE intellectual disability (MONDO:0010659), neurodevelopmental disorder (MONDO:0700092), cystic fibrosis (MONDO:0009061), mitochondrial complex I deficiency, nuclear type 21 (MONDO:0032625), hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation (MONDO:0015801), squamous cell carcinoma (MONDO:0005096), hereditary angioedema with normal C1Inh (MONDO:0100567)

Orphanet (5): Alpha-1-antitrypsin deficiency (Orphanet:60), FRAXE intellectual disability (Orphanet:100973), Cystic fibrosis (Orphanet:586), Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation (Orphanet:178396), Hereditary angioedema with normal C1Inh (Orphanet:528647)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Nephrolithiasis
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000952	Jaundice
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001402	Hepatocellular carcinoma
HP:0001409	Portal hypertension
HP:0001508	Failure to thrive
HP:0001531	Failure to thrive in infancy
HP:0001738	Exocrine pancreatic insufficiency
HP:0001744	Splenomegaly
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002035	Rectal prolapse
HP:0002094	Dyspnea
HP:0002097	Emphysema
HP:0002099	Asthma
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002570	Steatorrhea

GWAS associations

56 associations (top):

Study	Trait	p-value
GCST001613_6	Antineutrophil cytoplasmic antibody-associated vasculitis	2.000000e-09
GCST001639_8	Metabolite levels	5.000000e-48
GCST002932_11	Manganese levels	6.000000e-06
GCST003262_839	Post bronchodilator FEV1	1.000000e-06
GCST003264_42	Post bronchodilator FEV1/FVC ratio	1.000000e-08
GCST003976_4	Antineutrophil cytoplasmic antibody-associated vasculitis	3.000000e-12
GCST003985_19	Breast size	5.000000e-07
GCST004603_141	Platelet count	4.000000e-09
GCST004940_1	Alanine transaminase levels	2.000000e-10
GCST005162_2	Glucagon levels in response to oral glucose tolerance test (fasting)	1.000000e-06
GCST005194_150	Coronary artery disease	5.000000e-10
GCST005195_77	Coronary artery disease	8.000000e-10
GCST005908_23	Height	6.000000e-78
GCST006309_7	Post bronchodilator percent predicted FEV1 in smoking	4.000000e-08
GCST006310_5	Post bronchodilator FEV1/FVC ratio in smoking	1.000000e-08
GCST006612_6	LDL cholesterol	1.000000e-18
GCST006614_72	Total cholesterol levels	3.000000e-16
GCST007209_2	Gallstone disease	2.000000e-17
GCST007328_41	Alcohol consumption (drinks per week)	7.000000e-10
GCST007615_3	C-reactive protein levels	2.000000e-10
GCST007991_1	Large artery stroke	6.000000e-09
GCST008163_173	Height	1.000000e-07
GCST008522_10	Bitter alcoholic beverage consumption	9.000000e-08
GCST008757_19	Alcohol consumption	4.000000e-12
GCST008761_11	Sucrose liking	4.000000e-06
GCST008811_26	Alcohol consumption (drinks per week)	2.000000e-11
GCST009159_3	Blood protein levels	3.000000e-12
GCST009651_1	Serum alpha-fetoprotein levels	1.000000e-47
GCST009651_2	Serum alpha-fetoprotein levels	8.000000e-38
GCST009652_26	Serum alkaline phosphatase levels	3.000000e-17

EFO canonical traits (24, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0004309	platelet count
EFO:0004307	glucose tolerance test
EFO:0008463	glucagon measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004458	C-reactive protein measurement
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0010157	sucrose liking measurement
EFO:0004747	protein measurement
EFO:0004813	alpha globulin measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0004346	neuroimaging measurement
EFO:0006334	total iron binding capacity
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0009749	age at first sexual intercourse measurement
EFO:0007986	reticulocyte count
EFO:0007985	platelet crit
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213
D065886	Neurodevelopmental Disorders	F03.625
D029424	Pulmonary Disease, Chronic Obstructive	C08.381.495.389; C23.550.291.500.875
D019896	alpha 1-Antitrypsin Deficiency	C06.552.074; C08.381.112; C16.320.060; C23.550.325.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs28929474	SERPINA1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	9
Estradiol	affects reaction, increases expression, affects expression, affects cotreatment, decreases expression	5
Dexamethasone	affects expression, decreases expression, increases N-linked glycosylation	3
Nickel	affects binding, increases expression	3
Valproic Acid	affects expression, decreases expression	3
methylmercuric chloride	decreases expression	2
Acetaminophen	increases expression, decreases expression	2
Asbestos	increases response to substance	2
Cadmium	affects cotreatment, increases expression, affects binding	2
Smoke	increases expression, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression, affects cotreatment	2
Genistein	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects expression	1
deoxynivalenol	decreases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
sodium bichromate	decreases expression	1
afimoxifene	increases expression	1
cobaltous chloride	decreases secretion	1
Bisecurin I	increases expression	1
chromic chloride	decreases activity	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	increases acetylation, increases expression	1
potassium chromate(VI)	decreases expression	1
zinc sulfide	affects cotreatment, increases expression	1
ursodoxicoltaurine	increases activity, increases cleavage, decreases reaction	1
nivalenol	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1

Cellosaurus cell lines

69 cell lines: 53 induced pluripotent stem cell, 8 transformed cell line, 5 cancer cell line, 3 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5B10	GM14702	Transformed cell line	Male
CVCL_A1NY	CAMi014-A	Induced pluripotent stem cell	Male
CVCL_B0YW	Abcam SW480 SERPINA1 KO	Cancer cell line	Male
CVCL_B5V8	CET.IPS.FFALP1-500	Induced pluripotent stem cell	Female
CVCL_B6DM	TMHepTG2984 2	Cancer cell line
CVCL_B6DP	TMhep39	Cancer cell line
CVCL_B6DQ	TMhep48	Cancer cell line
CVCL_C1PU	HHUUKDi011-A	Induced pluripotent stem cell	Male
CVCL_C1PV	HHUUKDi012-A	Induced pluripotent stem cell	Female
CVCL_C932	RC2 100 3	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00396006	PHASE4	COMPLETED	Efficacy and Safety Study of Augmentation Therapy With ARALAST Fraction IV-1 (Human Alpha 1 - Proteinase Inhibitor)
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