TCIRG1

Summary

TCIRG1 (T cell immune regulator 1, ATPase H+ transporting V0 subunit a3, HGNC:11647) is a protein-coding gene on chromosome 11q13.2, encoding V-type proton ATPase 116 kDa subunit a 3 (Q13488). Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.

This gene encodes a subunit of a large protein complex known as a vacuolar H+-ATPase (V-ATPase). The protein complex acts as a pump to move protons across the membrane. This movement of protons helps regulate the pH of cells and their surrounding environment. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. V-ATPase is comprised of a cytosolic V1 domain and a transmembrane V0 domain. Alternative splicing results in multiple transcript variants. Mutations in this gene are associated with infantile malignant osteopetrosis.

Source: NCBI Gene 10312 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive osteopetrosis 1 (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,777 total — 103 pathogenic, 115 likely-pathogenic
• Phenotypes (HPO): 127
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_006019

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11647
Approved symbol	TCIRG1
Name	T cell immune regulator 1, ATPase H+ transporting V0 subunit a3
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	TIRC7, OC-116, OC116, ATP6N1C, Atp6i, a3, ATP6V0A3
Ensembl gene	ENSG00000110719
Ensembl biotype	protein_coding
OMIM	604592
Entrez	10312

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 9 retained_intron, 8 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000265686, ENST00000524598, ENST00000524870, ENST00000525516, ENST00000525724, ENST00000527530, ENST00000528981, ENST00000529364, ENST00000529657, ENST00000530063, ENST00000530449, ENST00000530802, ENST00000532635, ENST00000533005, ENST00000533947, ENST00000534673, ENST00000698254, ENST00000698255, ENST00000698256, ENST00000698257, ENST00000698258, ENST00000698259

RefSeq mRNA: 3 — MANE Select: NM_006019 NM_001351059, NM_006019, NM_006053

CCDS: CCDS53670, CCDS8177

Canonical transcript exons

ENST00000265686 — 20 exons

Exon	Start	End
ENSE00000904464	68041268	68041388
ENSE00001117234	68043371	68043497
ENSE00001166885	68050741	68050895
ENSE00001270148	68042946	68043031
ENSE00001363096	68039025	68039119
ENSE00003460979	68047882	68047972
ENSE00003471238	68049962	68050066
ENSE00003500401	68047433	68047572
ENSE00003533730	68049663	68049788
ENSE00003558602	68043814	68043907
ENSE00003560131	68044958	68045102
ENSE00003560655	68050487	68050664
ENSE00003561326	68044132	68044344
ENSE00003586583	68041753	68041831
ENSE00003608479	68047647	68047804
ENSE00003625276	68042643	68042863
ENSE00003630548	68043571	68043653
ENSE00003655865	68050137	68050254
ENSE00003670582	68048879	68048997
ENSE00003690304	68049081	68049294

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.6843 / max 684.2413, expressed in 1790 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115518	29.8511	1776
115517	1.8909	1100
115521	0.7958	311
115519	0.0922	20
115520	0.0544	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.52	gold quality
blood	UBERON:0000178	99.36	gold quality
spleen	UBERON:0002106	99.31	gold quality
body of pancreas	UBERON:0001150	99.30	gold quality
right adrenal gland cortex	UBERON:0035827	99.01	gold quality
right adrenal gland	UBERON:0001233	98.99	gold quality
left adrenal gland cortex	UBERON:0035825	98.89	gold quality
left adrenal gland	UBERON:0001234	98.82	gold quality
endocervix	UBERON:0000458	98.69	gold quality
mucosa of stomach	UBERON:0001199	98.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.51	gold quality
upper lobe of left lung	UBERON:0008952	98.44	gold quality
right lung	UBERON:0002167	98.41	gold quality
mucosa of transverse colon	UBERON:0004991	98.36	gold quality
monocyte	CL:0000576	98.30	gold quality
right uterine tube	UBERON:0001302	98.23	gold quality
body of uterus	UBERON:0009853	98.21	gold quality
left uterine tube	UBERON:0001303	98.20	gold quality
leukocyte	CL:0000738	98.14	gold quality
vermiform appendix	UBERON:0001154	98.10	gold quality
fundus of stomach	UBERON:0001160	98.10	gold quality
small intestine	UBERON:0002108	98.09	gold quality
transverse colon	UBERON:0001157	98.04	gold quality
body of stomach	UBERON:0001161	98.04	gold quality
ectocervix	UBERON:0012249	97.90	gold quality
right coronary artery	UBERON:0001625	97.77	gold quality
minor salivary gland	UBERON:0001830	97.75	gold quality
bone marrow	UBERON:0002371	97.69	gold quality
bone element	UBERON:0001474	97.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.68	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.59
E-CURD-112	yes	15.37
E-MTAB-10042	yes	10.13
E-MTAB-7606	no	659.74
E-GEOD-70580	no	520.60
E-MTAB-5061	no	3.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF6, ELF4, FOSL2, HIF1A, JUN, JUND, MYC, NFKB1, PARP1

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• localization to chromosome 11q12-13 in autosomal dominant osteopetrosis type I (PMID:12054167)
• Sibling pair linkage and association studies between peak bone mineral density and the gene locus for the osteoclast-specific subunit (OC116) of the vacuolar proton pump on chromosome 11p12-13. (PMID:12161516)
• Four novel single nucleotide mutations in the TCIRG1 gene encoding the 116-kDa osteoclast specific subunit of ATP6I affecting splice acceptor or donor sites result in aberrant transcription products. (PMID:12552563)
• There is an association between a polymorphism affecting an API binding site in the promoter of the TCIRG1 gene and bone mass in Scottish women. (PMID:14523594)
• 9 new TCIRG1 mutations were found in recessive osteopetrosis pts. 30% of the pts had c.1674-1G>A (aberrant splicing: r.1674_1884del) or c.2005C>T (protein variation: p.Arg669X). 40% were splicing regulatory sequence substitutions. (PMID:15300850)
• we validated by RT-PCR six new alternative splice events in TCIRG1 in most of the 28 human tissues studied (PMID:15809087)
• TIRC7 acts as an upstream regulatory molecule of cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression. (PMID:17082597)
• HLA-DR alpha 2 domain (sHLA-DRalpha2) induces negative signals by engaging TIRC7 on lymphocytes, inhibiting proliferation and inducing apoptosis in CD4+ and CD8+ T-cells via activation of the intrinsic pathway (PMID:18270567)
• analysis of a novel Alu-Alu recombination-mediated genomic deletion in the TCIRG1 gene in five osteopetrotic patients (PMID:18715141)
• Linkage disequilibrium (LD) mapping of the OPTB locus at the TCIRG1 region and found a unique splice site mutation c.807+5G>A in all Chuvashian OPTB patients studied. (PMID:19172990)
• Mutations in TCIRG1, OSTM1, ClCN7, and TNFRSF11A genes were detected in nine, three, one, and one patientswith infantile malignant osteopetrosis, respectively. (PMID:19507210)
• That the CLCN7 mutations provoke a phenotype as severe as the one caused by TCIRG1 loss of function suggests the affected residues to be crucial for the function of the ClC-7 chloride channel or chloride/proton-exchanger (PMID:20424301)
• V-ATPase localization and activity in kidney cells is regulated via direct PKA-dependent phosphorylation of the A subunit at Ser-175 (PMID:20525692)
• The novel mutation c.242delC of TCIRG1 in infantile malignant osteopetrosis (PMID:21042819)
• Our data highlights the importance of two large genomic deletions and mutations in the 5’ UTR with respect to patient management and, more critically, to prenatal diagnosis (PMID:22231430)
• The N termini of a-subunit isoforms are involved in signaling between vacuolar H+-ATPase (V-ATPase) and cytohesin-2 (PMID:23288846)
• The function of vacuolar ATPase (V-ATPase) a subunit isoforms in invasiveness of MCF10a and MCF10CA1a human breast cancer cells. (PMID:24072707)
• analysis demonstrates that CLCN7 and TCIRG1 mutations differentially affect bone matrix mineralization, and that there is a need to modify the current classification of osteopetrosis (PMID:24108692)
• TIRC7 is involved in inflammation in multiple sclerosis and anti-TIRC7 mAb can prevent immune activation via selective inhibition of Th1- and Th17-associated cytokine expression. (PMID:24526664)
• TIRC7 might be associated with the pathogenesis of ITP, and TIRC7 levels could be used as an indicator to evaluate patients’ response to HD-DXM treatment. (PMID:24617318)
• TCIRG1-associated congenital neutropenia. (PMID:24753205)
• Data indicate that the effects of epiregulin (EREG) and V-ATPase (TCIRG1) single nucleotide polymorphism (SNP) on pulmonary tuberculosis susceptibility, to the extent that they exist, are dependent on gene-gene interactions in West African populations. (PMID:24898387)
• An A to T transversion in the fourth base of the intron 2 donor splice site (c.117+4A–>T) in TCIRG1 in the Ashkenazi Jewish (AJ) population was found to be responsible for osteopetrosis. (PMID:24989235)
• Increased expression of TIRC7 in plasma was associated with the severity of acute graft-versus-host disease. (PMID:25623380)
• an intronic region in TCIRG1 that seems to be particularly prone to splicing mutations, allowing the production of a small amount of protein sufficient to reduce the severity of the phenotype usually associated with TCIRG1 defects. (PMID:25829125)
• TIRC7 might be involved in the pathogenesis of aplastic anemia. (PMID:26049920)
• The highly invasive human breast cancer cell lines express higher levels of the a3 isoform than poorly invasive lines; knockdown of a3 reduces both expression of V-ATPases at the plasma membrane and in vitro invasion of breast tumor cells. (Review) (PMID:26906430)
• In this study, whole exome sequencing (WES) was successfully used in six patients with malignant infantile osteopetrosis (MIOP) and identified mutations in four MIOP-related genes (CLCN7, TCIRG1, SNX10, and TNFRSF11A). (PMID:27187610)
• Nine rare missense variants at evolutionarily conserved sites in TCIRG1 are associated with lower absolute neutrophil count. (PMID:27229898)
• TCIRG1 gene mutation in a Chinese family is associated with infantile malignant osteopetrosis. (PMID:28604959)
• The aim of this study was to develop a clinically applicable lentiviral vector expressing TCIRG1 to correct osteoclast function in Infantile malignant osteopetrosis (PMID:28726516)
• TCIRG1 may be involved in endolysosomal transport-a process known to be important to development of early onset AD. (PMID:28738127)
• Case Reports: TCIRG1-dependent osteopetrosis with a mild clinical course in Chinese patients. (PMID:28816234)
• Since a3 subunit of V-ATPase complex plays a crucial role in bone resorption process, structurally abnormal a3 subunit might have adversely affected bone resorption process, leading to infantile osteopetrosis in Pakistani family. (PMID:29237407)
• TCIRG1 functions as a metastasis-enhancing gene by modulating cellular growth and epithelial-mesenchymal transition in the hepatocellular carcinoma progression. (PMID:29303507)
• TCIRG1 mutation is associated with osteopetrosis. (PMID:30431110)
• mutations in SLC29A3 and TCIRG1 in patients with Sclerosing bone dysplasias with hallmarks of dysosteosclerosis. (PMID:30537558)
• The study revealed that five of the twelve cases of autosomal recessive osteopetrosis carry at least one mutation of TCIRG1 gene. (PMID:30898715)
• Novel c.G630A TCIRG1 mutation causes aberrant splicing resulting in an unusually mild form of autosomal recessive osteopetrosis. (PMID:31111556)
• The Vacuolar H(+) ATPase alpha3 Subunit Negatively Regulates Migration and Invasion of Human Pancreatic Ductal Adenocarcinoma Cells. (PMID:32085585)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcirg1a	ENSDARG00000016835
danio_rerio	tcirg1b	ENSDARG00000105142
mus_musculus	Tcirg1	ENSMUSG00000001750
rattus_norvegicus	Tcirg1	ENSRNOG00000017220
drosophila_melanogaster	Vha100-3	FBGN0028669

Paralogs (3): ATP6V0A1 (ENSG00000033627), ATP6V0A4 (ENSG00000105929), ATP6V0A2 (ENSG00000185344)

Protein

Protein identifiers

V-type proton ATPase 116 kDa subunit a 3 — Q13488 (reviewed: Q13488)

Alternative names: Osteoclastic proton pump 116 kDa subunit, T-cell immune regulator 1, T-cell immune response cDNA7 protein, Vacuolar proton translocating ATPase 116 kDa subunit a isoform 3

All UniProt accessions (10): Q13488, A0A8V8TM28, A0A8V8TN16, A0A8V8TNB5, E9PM12, E9PMC5, E9PNA6, H0YCE3, H0YEL3, Q8TCH1

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment. Seems to be directly involved in T-cell activation.

Subunit / interactions. V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c’’, rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR.

Subcellular location. Membrane.

Tissue specificity. Isoform long is highly expressed in osteoclastomas. Isoform short is highly expressed in thymus.

Disease relevance. Osteopetrosis, autosomal recessive 1 (OPTB1) [MIM:259700] A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the V-ATPase 116 kDa subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13488-1	Long	yes
Q13488-2	Short

RefSeq proteins (3): NP_001337988, NP_006010, NP_006044 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002490	V-ATPase_116kDa_su	Family
IPR026028	V-type_ATPase_116kDa_su_euka	Family

Pfam: PF01496

UniProt features (31 total): topological domain 9, transmembrane region 8, sequence variant 8, region of interest 2, sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13488-F1	83.52	0.40

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1222556	ROS and RNS production in phagocytes
R-HSA-6798695	Neutrophil degranulation
R-HSA-77387	Insulin receptor recycling
R-HSA-917977	Transferrin endocytosis and recycling
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-983712	Ion channel transport

MSigDB gene sets: 605 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_VACUOLE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, GOBP_INSULIN_SECRETION, GOBP_T_CELL_HOMEOSTASIS

GO Biological Process (45): autophagosome assembly (GO:0000045), ossification (GO:0001503), osteoclast proliferation (GO:0002158), intracellular calcium ion homeostasis (GO:0006874), apoptotic process (GO:0006915), inflammatory response (GO:0006954), cellular defense response (GO:0006968), vacuolar acidification (GO:0007035), protein catabolic process in the vacuole (GO:0007039), lysosomal lumen acidification (GO:0007042), positive regulation of cell population proliferation (GO:0008284), regulation of proton transport (GO:0010155), response to silver ion (GO:0010272), gene expression (GO:0010467), regulation of gene expression (GO:0010468), immunoglobulin mediated immune response (GO:0016064), macroautophagy (GO:0016236), optic nerve development (GO:0021554), establishment of cell polarity (GO:0030010), B cell differentiation (GO:0030183), T cell differentiation (GO:0030217), osteoclast differentiation (GO:0030316), ruffle organization (GO:0031529), memory T cell activation (GO:0035709), T-helper 1 cell activation (GO:0035711), T cell homeostasis (GO:0043029), tooth eruption (GO:0044691), bone resorption (GO:0045453), regulation of osteoblast differentiation (GO:0045667), pH reduction (GO:0045851), regulation of insulin secretion (GO:0050796), establishment of vesicle localization (GO:0051650), retina development in camera-type eye (GO:0060041), hematopoietic stem cell homeostasis (GO:0061484), enamel mineralization (GO:0070166), cellular response to cytokine stimulus (GO:0071345), phagosome acidification (GO:0090383), dentin mineralization (GO:0097188), proton transmembrane transport (GO:1902600), monoatomic ion transport (GO:0006811)

GO Molecular Function (3): proton-transporting ATPase activity, rotational mechanism (GO:0046961), ATPase binding (GO:0051117), protein binding (GO:0005515)

GO Cellular Component (16): vacuolar proton-transporting V-type ATPase, V0 domain (GO:0000220), nucleus (GO:0005634), lysosomal membrane (GO:0005765), late endosome (GO:0005770), plasma membrane (GO:0005886), endosome membrane (GO:0010008), apical plasma membrane (GO:0016324), vacuolar proton-transporting V-type ATPase complex (GO:0016471), phagocytic vesicle membrane (GO:0030670), proton-transporting V-type ATPase complex (GO:0033176), ficolin-1-rich granule membrane (GO:0101003), lysosome (GO:0005764), membrane (GO:0016020), secretory granule membrane (GO:0030667), proton-transporting V-type ATPase, V0 domain (GO:0033179), phagocytic vesicle (GO:0045335)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Innate Immune System	2
Signaling by Insulin receptor	1
Iron uptake and transport	1
Cellular response to starvation	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	2
vacuolar membrane	2
endosome	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
proton-transporting V-type ATPase complex	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
multicellular organismal process	1
leukocyte proliferation	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
intracellular pH reduction	1
vacuole	1
protein catabolic process	1
vacuolar acidification	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
proton transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
response to metal ion	1
macromolecule biosynthetic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
B cell mediated immunity	1
autophagosome assembly	1
autophagy	1
cranial nerve development	1
establishment or maintenance of cell polarity	1
lymphocyte differentiation	1
B cell activation	1

Protein interactions and networks

STRING

1788 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCIRG1	ATP6V1B1	P15313	979
TCIRG1	CLCN7	P51798	965
TCIRG1	OSTM1	Q86WC4	964
TCIRG1	ATP12A	P54707	923
TCIRG1	ATP4A	P20648	923
TCIRG1	PLEKHM1	Q9Y4G2	889
TCIRG1	CA2	P00918	869
TCIRG1	CCKBR	P32239	817
TCIRG1	ATP6V1B2	P21281	797
TCIRG1	ATP6V0C	P27449	792
TCIRG1	ATP6V0D2	Q8N8Y2	792
TCIRG1	ATP6V1C1	P21283	782
TCIRG1	ATP6V0D1	P12953	779
TCIRG1	ATP6V1A	P38606	773
TCIRG1	ATP6V1C2	Q8NEY4	773

IntAct

52 interactions, top by confidence:

A	B	Type	Score
ATP6AP2	ATP6V0C	psi-mi:“MI:0914”(association)	0.730
TCIRG1	ATP6AP2	psi-mi:“MI:0914”(association)	0.640
ATP6V1C2	ATP6V1G1	psi-mi:“MI:0914”(association)	0.640
TLX3	TCIRG1	psi-mi:“MI:0915”(physical association)	0.560
POGZ	TCIRG1	psi-mi:“MI:0915”(physical association)	0.560
ADD2	ADD1	psi-mi:“MI:0914”(association)	0.560
ATP6AP2	ATP6V1C1	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
ATP6V1G2	ATP6V1B1	psi-mi:“MI:0914”(association)	0.530
GORASP1	PPP6R2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
MCAM	LGALS8	psi-mi:“MI:0914”(association)	0.530
RFFL	TUSC2	psi-mi:“MI:0914”(association)	0.530
pipB2	SCD	psi-mi:“MI:0914”(association)	0.460
PLEKHN1	TCIRG1	psi-mi:“MI:0915”(physical association)	0.400
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
TCIRG1	KCNK1	psi-mi:“MI:0915”(physical association)	0.370
TCIRG1	TERF1	psi-mi:“MI:0915”(physical association)	0.370
SYNCRIP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
BAG6	CNOT1	psi-mi:“MI:0914”(association)	0.350
SORT1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
GOLT1B		psi-mi:“MI:0914”(association)	0.350
ATP6V0D1		psi-mi:“MI:0914”(association)	0.350
ATP6V0D2	ATP6V0C	psi-mi:“MI:0914”(association)	0.350
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (91): TCIRG1 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), TCIRG1 (Reconstituted Complex), TCIRG1 (Protein-RNA), TCIRG1 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), POGZ (Two-hybrid)

ESM2 similar proteins: A4FUB8, E9QBI7, O35394, O95070, O97681, P15920, P58872, P58873, Q0DWA9, Q0P5E4, Q12270, Q12893, Q13488, Q1RMH4, Q28C60, Q3UVK0, Q4V8F3, Q52NJ0, Q5RBS4, Q5XIT3, Q5Z413, Q6BSA9, Q6C741, Q6CDV6, Q6CR06, Q6DCK1, Q6FSG0, Q6P6G5, Q6UPR8, Q755H8, Q7Z2K6, Q874X5, Q8BHC7, Q8BXJ9, Q8RXQ2, Q8TEB9, Q8VC82, Q8VZ96, Q91VU1, Q91XB7

Diamond homologs: A1A5G6, B2MZD0, G5EEK9, G5EGP4, O13742, O29106, O57721, O97681, P15920, P25286, P30628, P32563, P37296, Q01290, Q13488, Q29466, Q54E04, Q57675, Q5JDS2, Q5R422, Q8AVM5, Q8RWZ7, Q8W4S4, Q920R6, Q93050, Q9HBG4, Q9I8D0, Q9SJT7, Q9UWW3, Q9UXU2, Q9Y487, Q9Z1G4, Q9YEA0, O27041, O83544, Q9RWH3, Q9HND8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TCIRG1	“form complex”	V-ATPase	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	5	68.5×	4e-07
Insulin receptor recycling	8	62.1×	6e-11
Transferrin endocytosis and recycling	8	60.1×	6e-11
ROS and RNS production in phagocytes	8	54.8×	9e-11
Amino acids regulate mTORC1	8	32.7×	6e-09
Ion channel transport	8	15.7×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle lumen acidification	7	102.4×	1e-10
vacuolar acidification	5	57.2×	4e-06
regulation of macroautophagy	8	37.0×	1e-08
proton transmembrane transport	5	24.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1777 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	103
Likely pathogenic	115
Uncertain significance	614
Likely benign	765
Benign	26

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068788	NM_006019.4(TCIRG1):c.797del (p.Glu266fs)	Pathogenic
1069133	NM_006019.4(TCIRG1):c.685G>T (p.Gly229Ter)	Pathogenic
1070235	NM_006019.4(TCIRG1):c.2233dup (p.Ala745fs)	Pathogenic
1074841	NM_006019.4(TCIRG1):c.524_527dup (p.His177fs)	Pathogenic
1075445	NM_006019.4(TCIRG1):c.1349dup (p.Met450fs)	Pathogenic
1362729	NM_006019.4(TCIRG1):c.480del (p.Pro161fs)	Pathogenic
1388769	NM_006019.4(TCIRG1):c.1498del (p.Leu500fs)	Pathogenic
1418205	NM_006019.4(TCIRG1):c.1776G>A (p.Trp592Ter)	Pathogenic
1439125	NM_006019.4(TCIRG1):c.904_952del (p.Val302fs)	Pathogenic
1447238	NM_006019.4(TCIRG1):c.2383_2384del (p.Ala796fs)	Pathogenic
1447247	NM_006019.4(TCIRG1):c.2160_2178del (p.Ile721fs)	Pathogenic
1449740	NC_000011.9:g.(?67814890)(67815449_?)del	Pathogenic
1451544	NM_006019.4(TCIRG1):c.1736del (p.Gly579fs)	Pathogenic
1452936	NM_006019.4(TCIRG1):c.1230del (p.Leu411fs)	Pathogenic
1453401	NM_006019.4(TCIRG1):c.474dup (p.Gly159fs)	Pathogenic
1453967	NM_006019.4(TCIRG1):c.2331dup (p.Ala778fs)	Pathogenic
1455306	NC_000011.9:g.(?67814890)(67818296_?)del	Pathogenic
1457984	NM_006019.4(TCIRG1):c.174_175del (p.Cys58_Glu59delinsTer)	Pathogenic
1458624	NM_006019.4(TCIRG1):c.1348_1376dup (p.Phe459fs)	Pathogenic
1460225	NM_006019.4(TCIRG1):c.688C>T (p.Gln230Ter)	Pathogenic
1492118	NM_006019.4(TCIRG1):c.1305+1G>A	Pathogenic
1684665	NM_006019.4(TCIRG1):c.807+2T>G	Pathogenic
1684673	NM_006019.4(TCIRG1):c.969G>A (p.Trp323Ter)	Pathogenic
1684679	NM_006019.4(TCIRG1):c.2236+1G>C	Pathogenic
1684680	NM_006019.4(TCIRG1):c.1885C>T (p.Gln629Ter)	Pathogenic
189246	NM_006019.4(TCIRG1):c.1674-1G>A	Pathogenic
1913378	NM_006019.4(TCIRG1):c.1370_1384del (p.Thr457_Tyr461del)	Pathogenic
1980632	NM_006019.4(TCIRG1):c.1037_1040dup (p.Val348fs)	Pathogenic
1988317	NM_006019.4(TCIRG1):c.1560G>A (p.Trp520Ter)	Pathogenic
2008908	NM_006019.4(TCIRG1):c.2104_2105del (p.Glu702fs)	Pathogenic

SpliceAI

4169 predictions. Top by Δscore:

Variant	Effect	Δscore
11:68039117:GGG:G	donor_gain	1.0000
11:68039118:GG:G	donor_gain	1.0000
11:68039118:GGG:G	donor_gain	1.0000
11:68039119:GG:G	donor_gain	1.0000
11:68039120:G:GG	donor_gain	1.0000
11:68039120:GTGA:G	donor_loss	1.0000
11:68041261:C:G	acceptor_gain	1.0000
11:68041263:CACA:C	acceptor_loss	1.0000
11:68041264:ACAG:A	acceptor_gain	1.0000
11:68041266:A:AG	acceptor_gain	1.0000
11:68041266:AG:A	acceptor_gain	1.0000
11:68041267:G:GT	acceptor_gain	1.0000
11:68041267:GG:G	acceptor_gain	1.0000
11:68041267:GGA:G	acceptor_gain	1.0000
11:68041267:GGAC:G	acceptor_gain	1.0000
11:68041267:GGACC:G	acceptor_gain	1.0000
11:68041345:GC:G	donor_gain	1.0000
11:68041384:GAGAC:G	donor_gain	1.0000
11:68041386:GAC:G	donor_gain	1.0000
11:68041387:ACG:A	donor_loss	1.0000
11:68041389:G:GG	donor_gain	1.0000
11:68041747:CCACA:C	acceptor_loss	1.0000
11:68041748:CACA:C	acceptor_loss	1.0000
11:68041749:ACAG:A	acceptor_loss	1.0000
11:68041750:CA:C	acceptor_loss	1.0000
11:68041751:A:AC	acceptor_loss	1.0000
11:68041751:A:AG	acceptor_gain	1.0000
11:68041752:G:GA	acceptor_gain	1.0000
11:68041752:GCTC:G	acceptor_gain	1.0000
11:68041752:GCTCA:G	acceptor_gain	1.0000

AlphaMissense

5384 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:68050222:T:C	L735P	0.999
11:68050230:T:A	W738R	0.999
11:68050230:T:C	W738R	0.999
11:68048926:G:C	K534N	0.998
11:68048926:G:T	K534N	0.998
11:68050232:G:C	W738C	0.997
11:68050232:G:T	W738C	0.997
11:68050239:A:C	S741R	0.997
11:68050241:C:A	S741R	0.997
11:68050241:C:G	S741R	0.997
11:68050658:T:C	L803P	0.997
11:68050748:T:C	F808L	0.997
11:68050750:C:A	F808L	0.997
11:68050750:C:G	F808L	0.997
11:68050760:T:C	F812L	0.997
11:68050762:C:A	F812L	0.997
11:68050762:C:G	F812L	0.997
11:68047477:T:C	F404L	0.996
11:68047479:C:A	F404L	0.996
11:68047479:C:G	F404L	0.996
11:68048917:C:A	N531K	0.996
11:68048917:C:G	N531K	0.996
11:68050213:C:A	A732D	0.996
11:68050645:C:G	H799D	0.996
11:68050185:T:C	F723L	0.995
11:68050187:C:A	F723L	0.995
11:68050187:C:G	F723L	0.995
11:68050204:C:A	S729Y	0.995
11:68050204:C:T	S729F	0.995
11:68050216:C:T	S733F	0.995

dbSNP variants (sampled 300 via entrez): RS1000047233 (11:68037381 G>A,T), RS1000520573 (11:68051772 G>A,C), RS1000538925 (11:68043362 G>A), RS1000613230 (11:68044401 G>A), RS1000664757 (11:68048025 G>C), RS1000666892 (11:68047264 C>A,G,T), RS1000724351 (11:68048199 T>C), RS1000940711 (11:68037432 T>A,C), RS1001080626 (11:68037629 C>G), RS1001191391 (11:68038976 T>A,C), RS1001228717 (11:68043137 A>AG), RS1001671587 (11:68044470 G>C), RS1001985320 (11:68047771 G>A), RS1002118866 (11:68038095 C>T), RS1002149192 (11:68038508 G>A,C)

Disease associations

OMIM: gene MIM:604592 | disease phenotypes: MIM:259700, MIM:202700, MIM:224300, MIM:200150, MIM:618222

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive osteopetrosis 1	Definitive	Autosomal recessive
autosomal recessive osteopetrosis	Definitive	Autosomal recessive
dysosteosclerosis	Supportive	Autosomal recessive
autosomal recessive osteopetrosis 6	Supportive	Autosomal recessive
autosomal dominant severe congenital neutropenia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
autosomal recessive osteopetrosis 1	Definitive	AR
dysosteosclerosis	Limited	AR

Mondo (11): autosomal recessive osteopetrosis 1 (MONDO:0009815), osteopetrosis (MONDO:0017198), neutropenia, severe congenital, 1, autosomal dominant (MONDO:0042490), bone disorder (MONDO:0005381), neutropenia (MONDO:0001475), dysosteosclerosis (MONDO:0009138), autosomal recessive osteopetrosis (MONDO:0019026), VPS13A-related neurodegenerative disease (MONDO:0008695), mitochondrial complex I deficiency, nuclear type 2 (MONDO:0032606), autosomal recessive osteopetrosis 6 (MONDO:0012679), autosomal dominant severe congenital neutropenia (MONDO:0008742)

Orphanet (5): Autosomal recessive malignant osteopetrosis (Orphanet:667), Osteopetrosis and related disorders (Orphanet:2781), Rare bone disease related to a common gene or pathway defect (Orphanet:364803), Dysosteosclerosis (Orphanet:1782), Choreoacanthocytosis (Orphanet:2388)

HPO phenotypes

127 total (30 of 127 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000155	Oral ulcer
HP:0000164	Abnormality of the dentition
HP:0000230	Gingivitis
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000505	Visual impairment
HP:0000597	Ophthalmoparesis
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000670	Carious teeth
HP:0000682	Abnormal dental enamel morphology
HP:0000684	Delayed eruption of teeth
HP:0000689	Dental malocclusion
HP:0000704	Periodontitis
HP:0000707	Abnormality of the nervous system
HP:0000772	Abnormal rib morphology
HP:0000774	Narrow chest
HP:0000926	Platyspondyly
HP:0000938	Osteopenia
HP:0000944	Abnormal metaphysis morphology
HP:0000978	Bruising susceptibility
HP:0000980	Pallor
HP:0001028	Hemangioma
HP:0001249	Intellectual disability

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006979_403	Heel bone mineral density	2.000000e-12
GCST006979_404	Heel bone mineral density	7.000000e-11
GCST90002405_285	Reticulocyte count	3.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0007986	reticulocyte count

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D001847	Bone Diseases	C05.116
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564
D010022	Osteopetrosis	C05.116.099.708.702.678
C562973	Dysosteosclerosis (supp.)
C565969	Neutropenia, Severe Congenital, Autosomal Dominant 1 (supp.)
C564915	Osteopetrosis, Autosomal Recessive 1 (supp.)
C566931	Osteopetrosis, Autosomal Recessive 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — V-type ATPase

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	4
Air Pollutants	increases abundance, decreases expression, affects expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
Nickel	increases expression	2
Rotenone	increases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, increases expression	1
tamibarotene	increases expression	1
entinostat	increases expression, affects cotreatment	1
pinostrobin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	decreases expression	1
Temozolomide	decreases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects methylation	1
Aspirin	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Demecolcine	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D0M3	SYSUSCi004-A	Induced pluripotent stem cell	Male
CVCL_YB57	UNIBSi010-A	Induced pluripotent stem cell	Male
CVCL_YB58	UNIBSi010-B	Induced pluripotent stem cell	Male
CVCL_YB59	UNIBSi010-C	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00125723	PHASE4	COMPLETED	FIRST - Study of Pegfilgrastim Administered in the First and Subsequent Cycles of Myelosuppressive Chemotherapy
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00257790	PHASE4	COMPLETED	The Tobramycin Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01114165	PHASE4	COMPLETED	Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
NCT01135589	PHASE4	UNKNOWN	Micafungin Prevention Study for Fungal Disease in Child Receiving Allogenic Hematopoietic Stem Cell Transplantation
NCT01571518	PHASE4	UNKNOWN	Prevention of Neutropenia After Using G-CSF With TAC Chemotherapy
NCT02621905	PHASE4	COMPLETED	Steady-State Comparative Bioavailability Study in Prophylaxis Patients of Lozanoc® 50 mg With Sporanox® 100 mg
NCT02967341	PHASE4	UNKNOWN	Blood Draw Validation for Ciprofloxacin Pharmacokinetic Research in Pediatric Cancer Patients
NCT04009941	PHASE4	COMPLETED	Efficacy and Safety of 4.5mg PEG-rhG-CSF Per Cycle in Preventing Neutropenia After Intensive Chemotherapy for Breast Cancer
NCT04904614	PHASE4	COMPLETED	Letermovir Use in Heart Transplant Recipients
NCT05626530	PHASE4	RECRUITING	Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients
NCT06145321	PHASE4	ACTIVE_NOT_RECRUITING	Continuous Versus Bolus Administration of G-CSF in Children With Cancer
NCT00004402	PHASE3	COMPLETED	Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis
NCT00001338	PHASE3	COMPLETED	A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00002658	PHASE3	UNKNOWN	Combination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia
NCT00002719	PHASE3	COMPLETED	Combination Chemotherapy With or Without G-CSF in Treating Older Patients With Acute Myeloid Leukemia
NCT00003739	PHASE3	COMPLETED	Antibiotic Therapy With or Without G-CSF in Treating Children With Neutropenia and Fever Caused by Chemotherapy
NCT00020865	PHASE3	UNKNOWN	Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia
NCT00035594	PHASE3	COMPLETED	Pegfilgrastim as Support to Advanced Breast Cancer Patients Receiving Chemotherapy
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00107081	PHASE3	TERMINATED	Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
NCT00445497	PHASE3	UNKNOWN	Early Hospital Discharge or Standard Inpatient Care in Cancer Patients Receiving Antibiotics for Febrile Neutropenia
NCT00529282	PHASE3	TERMINATED	A Study of Ceftobiprole in Patients With Fever and Neutropenia.
NCT00627393	PHASE3	COMPLETED	Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)
NCT00770172	PHASE3	COMPLETED	G-CSF in Preventing Neutropenia in Patients With Solid Tumors Who Are Receiving Chemotherapy
NCT00784368	PHASE3	COMPLETED	A Pharmacokinetic Study of JK1211(Itraconazole [Itrizole]) Oral Solution in Participants With Deep Mycosis and Those With Febrile Neutropenia Suspected of Fungal Infection
NCT00806351	PHASE3	TERMINATED	An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Serious Fungal Infection Due To Candida In Patients With A Dysfunctional Immune System
NCT00911170	PHASE3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
NCT01307579	PHASE3	COMPLETED	Caspofungin Versus Fluconazole in Preventing Invasive Fungal Infections (IFI) in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia
NCT01371656	PHASE3	COMPLETED	Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
NCT01560195	PHASE3	UNKNOWN	A Study of Pegylated rhG-CSF as Support to Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy Receiving Chemotherapy
NCT01611051	PHASE3	COMPLETED	A Study Comparing Pegylated rhG-CSF and rhG-CSF as Support to Breast Cancer Patients Receiving Chemotherapy
NCT02238873	PHASE3	UNKNOWN	Pegfilgrastim on Day +3 Compared to Day +1 After Salvage Chemotherapy for Patients With Refractory or Relapsed Aggressive Lymphoma
NCT02414581	PHASE3	COMPLETED	Mouthwash With Chlorhexidine 0.12%/Ethyl Alcohol 7% Compared to Ethyl Alcohol 7%
NCT02643420	PHASE3	COMPLETED	SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)