CLCN7

Summary

CLCN7 (Cl-/H+ antiporter 7, HGNC:2025) is a protein-coding gene on chromosome 16p13.3, encoding H(+)/Cl(-) exchange transporter 7 (P51798). Slowly voltage-gated channel mediating the exchange of chloride ions against protons.

The product of this gene belongs to the CLC chloride channel family of proteins. Chloride channels play important roles in the plasma membrane and in intracellular organelles. This gene encodes chloride channel 7. Defects in this gene are the cause of osteopetrosis autosomal recessive type 4 (OPTB4), also called infantile malignant osteopetrosis type 2 as well as the cause of autosomal dominant osteopetrosis type 2 (OPTA2), also called autosomal dominant Albers-Schonberg disease or marble disease autosoml dominant. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. OPTA2 is the most common form of osteopetrosis, occurring in adolescence or adulthood.

Source: NCBI Gene 1186 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypopigmentation, organomegaly, and delayed myelination and development (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,460 total — 39 pathogenic, 47 likely-pathogenic
• Phenotypes (HPO): 117
• MANE Select transcript: NM_001287

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2025
Approved symbol	CLCN7
Name	Cl-/H+ antiporter 7
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CLC-7, OPTA2, CLC7, ClC-7, PPP1R63
Ensembl gene	ENSG00000103249
Ensembl biotype	protein_coding
OMIM	602727
Entrez	1186

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 17 protein_coding, 9 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000262318, ENST00000382745, ENST00000561665, ENST00000563642, ENST00000563822, ENST00000564568, ENST00000564968, ENST00000565092, ENST00000566812, ENST00000567139, ENST00000567789, ENST00000567836, ENST00000569851, ENST00000699947, ENST00000699948, ENST00000699950, ENST00000892992, ENST00000892993, ENST00000892994, ENST00000892995, ENST00000892996, ENST00000892997, ENST00000892998, ENST00000917692, ENST00000917693, ENST00000917694, ENST00000971708, ENST00000971709

RefSeq mRNA: 2 — MANE Select: NM_001287 NM_001114331, NM_001287

CCDS: CCDS32361

Canonical transcript exons

ENST00000382745 — 25 exons

Exon	Start	End
ENSE00000873605	1474834	1475028
ENSE00001164313	1449276	1449327
ENSE00001164316	1450497	1450666
ENSE00001164323	1451623	1451716
ENSE00001164337	1454411	1454465
ENSE00001164340	1455134	1455250
ENSE00001164344	1455731	1455795
ENSE00001164371	1459107	1459187
ENSE00001164377	1460418	1460527
ENSE00001164385	1460816	1460948
ENSE00001282049	1452755	1452893
ENSE00001282055	1453834	1453894
ENSE00002589154	1444935	1446717
ENSE00003491999	1448966	1449093
ENSE00003526329	1448355	1448484
ENSE00003556680	1465267	1465338
ENSE00003626913	1457694	1457756
ENSE00003639583	1461603	1461674
ENSE00003641446	1447006	1447086
ENSE00003643193	1456113	1456206
ENSE00003651088	1461405	1461470
ENSE00003655559	1447392	1447568
ENSE00003674545	1447655	1447714
ENSE00003693364	1448681	1448766
ENSE00003788156	1457254	1457337

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5983 / max 542.4659, expressed in 1816 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155849	21.4124	1812
155848	6.7009	1680
155845	0.3439	90
155847	0.1339	29
155846	0.0072	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	97.61	gold quality
right adrenal gland cortex	UBERON:0035827	97.24	gold quality
left adrenal gland cortex	UBERON:0035825	97.08	gold quality
right adrenal gland	UBERON:0001233	96.91	gold quality
adrenal cortex	UBERON:0001235	96.91	gold quality
left adrenal gland	UBERON:0001234	96.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.85	gold quality
stromal cell of endometrium	CL:0002255	96.66	gold quality
granulocyte	CL:0000094	96.55	gold quality
right lobe of thyroid gland	UBERON:0001119	96.40	gold quality
left lobe of thyroid gland	UBERON:0001120	96.06	gold quality
cerebellar hemisphere	UBERON:0002245	96.05	gold quality
spleen	UBERON:0002106	96.02	gold quality
cerebellar cortex	UBERON:0002129	95.96	gold quality
adrenal gland	UBERON:0002369	95.76	gold quality
adenohypophysis	UBERON:0002196	95.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.56	gold quality
right frontal lobe	UBERON:0002810	95.38	gold quality
thyroid gland	UBERON:0002046	95.29	gold quality
pituitary gland	UBERON:0000007	95.28	gold quality
body of stomach	UBERON:0001161	95.26	gold quality
endocervix	UBERON:0000458	95.10	gold quality
left testis	UBERON:0004533	95.03	gold quality
skin of leg	UBERON:0001511	95.01	gold quality
cerebellum	UBERON:0002037	94.96	gold quality
mucosa of stomach	UBERON:0001199	94.91	gold quality
upper lobe of left lung	UBERON:0008952	94.88	gold quality
monocyte	CL:0000576	94.86	gold quality
right testis	UBERON:0004534	94.85	gold quality
mononuclear cell	CL:0000842	94.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MITF

miRNA regulators (miRDB)

42 targeting CLCN7, 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-4283	100.00	66.42	2097
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-6776-5P	98.54	67.43	1304

Literature-anchored findings (GeneRIF, showing 40)

• clcn7 gene mutation is associated with intermediate autosomal recessive osteopetrosis (PMID:12522560)
• mutations in the CICN7 gene are responsible for autosomal dominant osteopetrosis, type II, an uncommon sclerosing bone disorder (PMID:12929941)
• ClCN7 mutations have roles in severe recessive, dominant, and intermediate osteopetrosis (PMID:14584882)
• ClC-7 has a role in causing autosomal dominant osteopetrosis type II (PMID:15111300)
• The study indicates that the V418M polymorphism of CLCN7 contributes to the genetic regulation of femoral neck BMD in women. (PMID:16234969)
• Significant association of CLCN7 polymorphisms with the variance of bone density in postmenopausal women with osteopetrosis. (PMID:16368748)
• Autosomal dominant osteopetrosis caused by mutations in the CLCN7 gene is a frequently symptomatic disease manifested by a high rate of fracture, osteomyelitis, visual loss, and occasional bone marrow failure. (PMID:17164308)
• ClC-7 is a Cl-/H+ antiporter; it constitutes the major Cl- permeability of lysosomes, and it is important in lysosomal acidification. (PMID:18449189)
• Genetic variation in the CLCN7 gene is not a major contributor to the variability in peak BMD at the femoral neck and lumber spine in healthy premenopausal white women and in white men (PMID:18755304)
• These data demonstrate that ClC-7 is essential for bone resorption, via its role in acidification of the lysosomes and resorption lacunae in osteoclasts (PMID:19070589)
• Findings suggest that the novel Glu798FS mutation in exon 25 and R767W in exon 24 in the CLCN7 gene were responsible for autosomal dominant osteopetrosis (type II) in two Chinese patients. (PMID:19288050)
• Mutations in TCIRG1, OSTM1, ClCN7, and TNFRSF11A genes were detected in nine, three, one, and one patientswith infantile malignant osteopetrosis, respectively. (PMID:19507210)
• results suggest that osteoclastic ClC7 Cl(-) channels are activated under extracellar acidification and suppressed in Clcn7 mutant associated with autosomal osteopetrosis type II during bone resorption. (PMID:19543743)
• We report on the fatal clinical course of a 3 year old male Turkish patient suffering from osteopetrosis caused by a homozygous mutation in the chloride channel gene ClCN7 with developing pancytopenia and severe neurological impairment. (PMID:19904698)
• The characterization of 25 unpublished patients has resulted in the identification of 20 novel mutations, including 11 missense mutations, 6 causing premature termination, 1 small deletion and 2 putative splice site defects and clinical heterogeneity. (PMID:19953639)
• 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)
• Elevated serum LDH isoenzymes and AST indicate a disturbance (of uncertain clinical significance) within multiple extraosseous tissues when there is CLCN7 deficiency. (PMID:20499337)
• Rat G213R ClC-7 is the analogue of human G215R ClC-7 responsible for autosomal dominant osteopetrosis type II. (PMID:20830208)
• The authors show that both the aminoterminus and transmembrane span of the Ostm1 beta-subunit are required for ClC-7 Cl(-)/H(+)-exchange, whereas the Ostm1 transmembrane domain suffices for its ClC-7-dependent trafficking to lysosomes. (PMID:21527911)
• Eight mutations, including two reported mutations (R767W and E798FS) and six novel mutations (E313K, A316G, R743W, G741R, W127G and S290F), were detected in the CLCN7 gene from 12 living autosomal dominant osteopetrosis type II patients. (PMID:21947783)
• recurrent p.Gly215Arg mutation and novel missense mutations p.Ala299Val and p.Trp319Arg in the CLCN7 gene were responsible for these three Chinese ADO-II families. (PMID:23953223)
• ClC-7 does not appear to be crucially involved in gastric acid secretion, which explains the absence of an osteopetrorickets phenotype in CLCN7-related osteopetrosis. (PMID:24103576)
• 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)
• the unusual clinical presentation observed in our patient with a mild clinical onset evolving towards a more serious clinical picture, is associated to two novel mutations on CLCN7 gene. (PMID:25410126)
• Results show that ClC-7 is strongly expressed in OUMS-27,a chondrocyte cell line and is responsible for Cl- current. Its downregulation during the hypoosmotic stress accompanying osteoarthritis progression is part of the complex etiology of the disease. (PMID:25943117)
• present findings suggest that the novel missense mutations V289L and A542V in the CLCN7 gene were responsible for autosomal dominant osteopetrosis (type II) in the two Chinese families. (PMID:26056022)
• The present study identified seven novel mutations of the CLCN7 gene and reported the first case of intermediate autosomal recessive osteopetrosis. with compound heterozygous mutation in the Chinese population. (PMID:26395888)
• study demonstrates a wide heterogeneity in the progression of the phenotypes and expanded the mutational spectrum for the CLCN7 gene (PMID:26477479)
• 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)
• Exome sequencing and Sanger sequencing were conducted in Han Chinese family members, some of whom had typical osteopetrosis, and a novel missense variant c.2350A>T (p.R784W) in the chloride channel 7 gene (CLCN7) was identified. (PMID:27325559)
• we identified a CLCN7 mutation in a family with autosomal dominant osteopetrosis, RTA, renal stones, epilepsy, and blindness. (PMID:27540713)
• The present study revealed three novel mutations, showed the dense but brittle sclerotic bones of an autosomal dominant osteopetrosis type II (OPTA2) patient, characterized OPTA2 symptoms from benign to fatal and reported a rare intermediate case of autosomal recessive 4 in a Chinese population. (PMID:28975865)
• This study was aimed to identify the underlying genetic cause of the disease in a Pakistani family segregating infantile malignant osteopetrosis in autosomal recessive pattern. Two novel homozygous missense variants were found in the same codon 204 of CLCN7 NM_001287.5:c.[610A>T;612C>G] predicting p.(Ser204Trp) variant in the protein. (PMID:29926385)
• CLCN7 mutation is associated with osteopetrosis. (PMID:30431110)
• These findings highlighted the vital role of clcn7 in zebrafish craniofacial bone and tooth development and mineralization, revealing novel insights for the causation of osteopetrosis with CLCN7 mutations. (PMID:30867839)
• Various mutations (R286W, Y746D, Y99C, G793R, E313K, c.22322A>G, P470L and K217X) in the CLCN7 gene were identified in six patients with familial osteopetrosis and one patient with sporadic osteopetrosis. (PMID:30942407)
• p.Tyr715Cys is a gain-of-function CLCN7 variant associated with developmental delay, organomegaly, and hypopigmentation from lysosomal hyperacidity, abnormal storage, and enlarged intracellular vacuoles. (PMID:31155284)
• Cryo-EM structure of the lysosomal chloride-proton exchanger CLC-7 in complex with OSTM1. (PMID:32749217)
• Identification and Characterization of a Novel CLCN7 Variant Associated with Osteopetrosis. (PMID:33105733)
• Pathobiologic Mechanisms of Neurodegeneration in Osteopetrosis Derived From Structural and Functional Analysis of 14 ClC-7 Mutants. (PMID:33125761)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	clcn7	ENSDARG00000019556
mus_musculus	Clcn7	ENSMUSG00000036636
rattus_norvegicus	Clcn7	ENSRNOG00000016976
drosophila_melanogaster	ClC-b	FBGN0033755
caenorhabditis_elegans		WBGENE00000533

Paralogs (8): CLCN6 (ENSG00000011021), CLCN4 (ENSG00000073464), CLCN3 (ENSG00000109572), CLCN2 (ENSG00000114859), CLCN5 (ENSG00000171365), CLCNKB (ENSG00000184908), CLCNKA (ENSG00000186510), CLCN1 (ENSG00000188037)

Protein

Protein identifiers

H(+)/Cl(-) exchange transporter 7 — P51798 (reviewed: P51798)

Alternative names: Chloride channel 7 alpha subunit, Chloride channel protein 7

All UniProt accessions (6): A0A8V8TPE0, A0A8V8TQF3, P51798, H0Y2M6, H3BNG8, I3L470

UniProt curated annotations — full annotation on UniProt →

Function. Slowly voltage-gated channel mediating the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the lysosome lumen and may be involved in maintaining lysosomal pH. The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The presence of conserved gating glutamate residues is typical for family members that function as antiporters.

Subunit / interactions. Chloride channel 7 are heteromers of alpha (CLCN7) and beta (OSTM1) subunits.

Subcellular location. Lysosome membrane.

Tissue specificity. Brain and kidney.

Disease relevance. Osteopetrosis, autosomal recessive 4 (OPTB4) [MIM:611490] 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. Osteopetrosis, autosomal dominant 2 (OPTA2) [MIM:166600] 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. OPTA2 is the most common form of osteopetrosis, occurring in adolescence or adulthood. It is characterized by sclerosis, predominantly involving the spine, the pelvis and the skull base. The disease is caused by variants affecting the gene represented in this entry. Hypopigmentation, organomegaly, and delayed myelination and development (HOD) [MIM:618541] An autosomal dominant pleiotropic syndrome characterized by skin and hair hypopigmentation, growth and developmental delay, organomegaly including enlarged liver, spleen and kidneys, delayed brain myelination and developmental deficit in motor skills. Skin and liver biopsies show cellular accumulation of large intracellular vacuoles. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the chloride channel (TC 2.A.49) family. ClC-7/CLCN7 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P51798-1	1	yes
P51798-2	2

RefSeq proteins (2): NP_001107803, NP_001278* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000644	CBS_dom	Domain
IPR001807	ClC	Family
IPR002249	CIC-7	Family
IPR014743	Cl-channel_core	Homologous_superfamily
IPR046342	CBS_dom_sf	Homologous_superfamily
IPR051280	Cl-channel/antiporter	Family

Pfam: PF00571, PF00654

Catalyzed reactions (Rhea), 1 shown:

• 2 chloride(in) + H(+)(out) = 2 chloride(out) + H(+)(in) (RHEA:29567)

UniProt features (138 total): sequence variant 38, helix 30, strand 23, transmembrane region 10, intramembrane region 7, sequence conflict 7, binding site 5, turn 3, short sequence motif 3, modified residue 3, topological domain 2, domain 2, site 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
9G6C	ELECTRON MICROSCOPY	1.8
7CQ5	ELECTRON MICROSCOPY	2.6
9G6E	ELECTRON MICROSCOPY	2.6
9G6D	ELECTRON MICROSCOPY	2.7
7JM7	ELECTRON MICROSCOPY	2.82
7CQ6	ELECTRON MICROSCOPY	3
7CQ7	ELECTRON MICROSCOPY	3.55
8HVT	ELECTRON MICROSCOPY	3.6
7BXU	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51798-F1	80.94	0.44

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 (2): 247 (mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking h(+) and cl(-) transport); 314 (mediates proton transfer from the protein to the inner aqueous phase)

Ligand- & substrate-binding residues (5): 204; 514; 602; 658–660; 783–786

Post-translational modifications (3): 9, 60, 801

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels

MSigDB gene sets: 421 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOCC_VACUOLAR_MEMBRANE, GOBP_INORGANIC_ANION_TRANSPORT, CHANDRAN_METASTASIS_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, GCM_PRKCG, JAZAG_TGFB1_SIGNALING_DN, GOBP_CHLORIDE_TRANSPORT, GOBP_TRANSEPITHELIAL_TRANSPORT, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_RESPONSE_TO_PH, DOUGLAS_BMI1_TARGETS_DN, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, GCM_VAV1

GO Biological Process (7): response to pH (GO:0009268), transepithelial chloride transport (GO:0030321), chloride transmembrane transport (GO:1902476), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (7): chloride channel activity (GO:0005254), ATP binding (GO:0005524), chloride:proton antiporter activity (GO:0062158), nucleotide binding (GO:0000166), protein binding (GO:0005515), chloride transmembrane transporter activity (GO:0015108), antiporter activity (GO:0015297)

GO Cellular Component (4): lysosomal membrane (GO:0005765), membrane (GO:0016020), chloride channel complex (GO:0034707), lysosome (GO:0005764)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Ion channel transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chloride transport	2
transport	2
chloride transmembrane transporter activity	2
response to abiotic stimulus	1
transepithelial transport	1
monoatomic anion transmembrane transport	1
monoatomic anion transport	1
inorganic anion transport	1
cellular process	1
monoatomic cation transmembrane transport	1
monoatomic anion channel activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
solute:inorganic anion antiporter activity	1
proton transmembrane transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
monoatomic anion transmembrane transporter activity	1
chloride transmembrane transport	1
secondary active transmembrane transporter activity	1
lysosome	1
lytic vacuole membrane	1
cellular anatomical structure	1
monoatomic ion channel complex	1
lytic vacuole	1

Protein interactions and networks

STRING

1613 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLCN7	OSTM1	Q86WC4	999
CLCN7	TCIRG1	Q13488	965
CLCN7	PLEKHM1	Q9Y4G2	908
CLCN7	ATP4A	P20648	834
CLCN7	ATP12A	P54707	826
CLCN7	CA2	P00918	804
CLCN7	TNFRSF11A	Q9Y6Q6	772
CLCN7	TNFSF11	O14788	768
CLCN7	SNX10	Q9Y5X0	719
CLCN7	CTSK	P43235	687
CLCN7	LRP5	O75197	650
CLCN7	MCOLN1	Q9GZU1	597
CLCN7	HEPACAM	Q14CZ8	593
CLCN7	ACP5	P13686	576
CLCN7	SYT7	O43581	566

IntAct

149 interactions, top by confidence:

A	B	Type	Score
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
OSTM1	CLCN7	psi-mi:“MI:0407”(direct interaction)	0.790
OSTM1	CLCN7	psi-mi:“MI:0915”(physical association)	0.790
CLCN7	OSTM1	psi-mi:“MI:0915”(physical association)	0.790
CDH1	CTNND1	psi-mi:“MI:0914”(association)	0.730
BIRC7	HTRA2	psi-mi:“MI:0914”(association)	0.640
NDUFA13	NDUFS8	psi-mi:“MI:0914”(association)	0.640
CLCN7	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
CLCN7	SLC38A7	psi-mi:“MI:0915”(physical association)	0.560
OPRM1	CLCN7	psi-mi:“MI:0915”(physical association)	0.560
CLCN7	GDAP1	psi-mi:“MI:0915”(physical association)	0.560
CD53	CLCN7	psi-mi:“MI:0915”(physical association)	0.560
CLCN7	AQP7	psi-mi:“MI:0915”(physical association)	0.560
CLCN7	KCNN3	psi-mi:“MI:0915”(physical association)	0.560
CLCN7	LYVE1	psi-mi:“MI:0915”(physical association)	0.560
CLCN7	SLC66A2	psi-mi:“MI:0915”(physical association)	0.560
CLCN7	TMEM179B	psi-mi:“MI:0915”(physical association)	0.560
GET1	CLCN7	psi-mi:“MI:0915”(physical association)	0.560
CLCN7	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
CLCN7	GLE1	psi-mi:“MI:0915”(physical association)	0.560
CLCN7	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
SLC15A4	CLCN7	psi-mi:“MI:0915”(physical association)	0.560
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530

BioGRID (229): CLCN7 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS), CLCN7 (Proximity Label-MS), CLCN7 (Proximity Label-MS), CLCN7 (Proximity Label-MS), CLCN7 (Two-hybrid), CLCN7 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS)

ESM2 similar proteins: A6NFX1, A6QQL0, D2HKB0, D3ZG27, F1NCD6, F1NJ67, O09014, O70496, O82390, P51798, P51799, Q17QZ3, Q1JQC1, Q32LQ6, Q3T9M1, Q3T9X0, Q3TIT8, Q4PKH3, Q504N2, Q58CV5, Q5F3N0, Q5R8G5, Q5RB09, Q5T4D3, Q5ZIT9, Q5ZKS8, Q66H95, Q68F72, Q69YG0, Q6AY78, Q6PDE8, Q7SY29, Q8BFQ6, Q8BG19, Q8GX78, Q8IVW8, Q8IZD6, Q8N697, Q8NCC5, Q8NEB5

Diamond homologs: O35454, O70496, P0C197, P51793, P51794, P51795, P51796, P51797, P51798, P51799, P92942, P92943, Q1ZXJ0, Q4PKH3, Q54AX6, Q5RBK4, Q61418, Q75JF3, Q86AZ6, Q8XTT4, Q96282, Q99P66, Q9GKE7, Q9TT16, Q9TTU3, Q9WVD4, O18894, P51790, P51791, P51792, P60300, P92941, Q5RDJ7, Q9R279, O60159, O94287, P35523, P35524, P37020, Q64347

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TFEB	“up-regulates quantity by expression”	CLCN7	“transcriptional regulation”
TFE3	“up-regulates quantity by expression”	CLCN7	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 153 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
Neutrophil degranulation	18	4.6×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

1460 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	39
Likely pathogenic	47
Uncertain significance	531
Likely benign	592
Benign	128

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012215	NM_001287.6(CLCN7):c.952T>C (p.Phe318Leu)	Pathogenic
1065115	NM_001287.6(CLCN7):c.1561G>A (p.Gly521Arg)	Pathogenic
1410271	NC_000016.9:g.(?1507235)(1524975_?)del	Pathogenic
1453932	NM_001287.6(CLCN7):c.746C>T (p.Pro249Leu)	Pathogenic
1458929	NM_001287.6(CLCN7):c.718G>A (p.Gly240Arg)	Pathogenic
1459594	NC_000016.10:g.1457356_1457357insATGCTCAGAGACACGCGTGACGCGGCCCTTCCTGGAGACCAGAAGGACCG	Pathogenic
1675596	NM_001287.6(CLCN7):c.1424dup (p.Ser476fs)	Pathogenic
1685637	NM_001287.6(CLCN7):c.2066del (p.Lys689fs)	Pathogenic
1685638	NM_001287.6(CLCN7):c.1562G>C (p.Gly521Ala)	Pathogenic
1701268	NM_001287.6(CLCN7):c.2053_2072delinsT (p.Ile685fs)	Pathogenic
2012245	NM_001287.6(CLCN7):c.1612dup (p.Ala538fs)	Pathogenic
2014467	NM_001287.6(CLCN7):c.2049dup (p.Leu684fs)	Pathogenic
2025971	NM_001287.6(CLCN7):c.381G>A (p.Trp127Ter)	Pathogenic
2036195	NM_001287.6(CLCN7):c.512del (p.Gly171fs)	Pathogenic
2049877	NM_001287.6(CLCN7):c.1147_1148insA (p.Val383fs)	Pathogenic
2128622	NM_001287.6(CLCN7):c.1270dup (p.Thr424fs)	Pathogenic
2137755	NM_001287.6(CLCN7):c.869C>T (p.Ser290Phe)	Pathogenic
2137756	NM_001287.6(CLCN7):c.811C>T (p.Arg271Ter)	Pathogenic
2424116	NC_000016.9:g.(?1496632)(1524975_?)del	Pathogenic
2664512	NM_001287.6(CLCN7):c.892dup (p.Ser298fs)	Pathogenic
2736274	NM_001287.6(CLCN7):c.637C>T (p.Leu213Phe)	Pathogenic
2840563	NM_001287.6(CLCN7):c.282T>G (p.Tyr94Ter)	Pathogenic
2846756	NM_001287.6(CLCN7):c.259G>T (p.Glu87Ter)	Pathogenic
2852015	NM_001287.6(CLCN7):c.1331dup (p.Ser445fs)	Pathogenic
3243623	NC_000016.9:g.(?1524815)(1524975_?)del	Pathogenic
3721940	NM_001287.6(CLCN7):c.2250+1G>A	Pathogenic
3721941	NM_001287.6(CLCN7):c.2134C>T (p.Arg712Ter)	Pathogenic
372326	NM_001287.6(CLCN7):c.2144A>G (p.Tyr715Cys)	Pathogenic
3901171	NM_001287.6(CLCN7):c.797C>G (p.Ser266Ter)	Pathogenic
4688721	NM_001287.6(CLCN7):c.1828_1829del (p.Ser610fs)	Pathogenic

SpliceAI

5383 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1447000:GCTCA:G	donor_loss	1.0000
16:1447001:CTCA:C	donor_loss	1.0000
16:1447002:TCA:T	donor_loss	1.0000
16:1447003:CACC:C	donor_loss	1.0000
16:1447005:C:CT	donor_loss	1.0000
16:1447082:GCCTC:G	acceptor_gain	1.0000
16:1447083:CCTCC:C	acceptor_gain	1.0000
16:1447084:CTC:C	acceptor_gain	1.0000
16:1447085:TC:T	acceptor_gain	1.0000
16:1447085:TCC:T	acceptor_loss	1.0000
16:1447086:CC:C	acceptor_gain	1.0000
16:1447086:CCT:C	acceptor_loss	1.0000
16:1447087:C:CC	acceptor_gain	1.0000
16:1447091:A:T	acceptor_gain	1.0000
16:1447377:ATGC:A	donor_gain	1.0000
16:1447424:A:AC	donor_gain	1.0000
16:1447425:C:CC	donor_gain	1.0000
16:1447448:C:CA	donor_gain	1.0000
16:1447456:T:TA	donor_gain	1.0000
16:1447564:AACAC:A	acceptor_gain	1.0000
16:1447565:ACAC:A	acceptor_gain	1.0000
16:1447566:CAC:C	acceptor_gain	1.0000
16:1447566:CACC:C	acceptor_gain	1.0000
16:1447567:AC:A	acceptor_gain	1.0000
16:1447568:CC:C	acceptor_gain	1.0000
16:1447568:CCT:C	acceptor_loss	1.0000
16:1447569:C:CC	acceptor_gain	1.0000
16:1447577:G:T	acceptor_gain	1.0000
16:1447651:GCAC:G	donor_loss	1.0000
16:1447652:CA:C	donor_loss	1.0000

AlphaMissense

5211 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1446698:C:A	R784M	1.000
16:1446710:C:T	G780E	1.000
16:1447031:A:G	L769P	1.000
16:1447043:C:T	G765D	1.000
16:1447665:A:G	L688P	1.000
16:1447677:A:G	L684P	1.000
16:1449046:C:G	A573P	1.000
16:1449057:A:T	I569N	1.000
16:1449060:A:T	V568D	1.000
16:1449066:A:G	L566P	1.000
16:1449068:G:C	S565R	1.000
16:1449068:G:T	S565R	1.000
16:1449070:T:G	S565R	1.000
16:1449278:A:G	L556P	1.000
16:1449284:G:T	A554D	1.000
16:1449293:C:T	G551E	1.000
16:1449294:C:G	G551R	1.000
16:1449294:C:T	G551R	1.000
16:1450540:C:T	G525D	1.000
16:1450541:C:G	G525R	1.000
16:1450544:A:G	W524R	1.000
16:1450544:A:T	W524R	1.000
16:1450552:C:T	G521E	1.000
16:1450553:C:A	G521W	1.000
16:1450553:C:G	G521R	1.000
16:1450553:C:T	G521R	1.000
16:1450561:A:G	L518P	1.000
16:1450580:C:A	G512W	1.000
16:1455757:A:G	W319R	1.000
16:1455757:A:T	W319R	1.000

dbSNP variants (sampled 300 via entrez): RS1000097648 (16:1450276 G>A), RS1000174399 (16:1457520 C>T), RS1000196945 (16:1448878 C>CG), RS1000227977 (16:1453690 G>C), RS1000272517 (16:1475598 C>T), RS1000347390 (16:1461124 C>T), RS1000353389 (16:1448724 G>T), RS1000716923 (16:1469195 G>C,T), RS1000729201 (16:1467216 C>G,T), RS1000742672 (16:1473679 C>A), RS1000748555 (16:1469063 G>A,C), RS1000908314 (16:1463456 A>T), RS1000952334 (16:1447539 C>G,T), RS1000965846 (16:1454658 G>A), RS1001180202 (16:1447306 C>A,G,T)

Disease associations

OMIM: gene MIM:602727 | disease phenotypes: MIM:166600, MIM:611490, MIM:618541, MIM:259700, MIM:266920

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant osteopetrosis 2	Definitive	Autosomal dominant
autosomal recessive osteopetrosis 4	Definitive	Autosomal recessive
hypopigmentation, organomegaly, and delayed myelination and development	Strong	Autosomal dominant
autosomal recessive osteopetrosis 6	Supportive	Autosomal recessive
autosomal recessive osteopetrosis	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (3)

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

Disease	Classification	Inheritance
hypopigmentation, organomegaly, and delayed myelination and development	Definitive	AD
autosomal dominant osteopetrosis 2	Definitive	AD
autosomal recessive osteopetrosis 4	Definitive	AR

Mondo (9): autosomal dominant osteopetrosis 2 (MONDO:0008156), autosomal recessive osteopetrosis 4 (MONDO:0012676), hypopigmentation, organomegaly, and delayed myelination and development (MONDO:0032805), bone disorder (MONDO:0005381), autosomal recessive osteopetrosis (MONDO:0019026), osteopetrosis (MONDO:0017198), short-rib thoracic dysplasia 9 with or without polydactyly (MONDO:0009964), connective tissue disorder (MONDO:0003900), autosomal recessive osteopetrosis 6 (MONDO:0012679)

Orphanet (5): Albers-Schönberg osteopetrosis (Orphanet:53), Autosomal recessive malignant osteopetrosis (Orphanet:667), Rare bone disease related to a common gene or pathway defect (Orphanet:364803), Osteopetrosis and related disorders (Orphanet:2781), Saldino-Mainzer syndrome (Orphanet:140969)

HPO phenotypes

117 total (30 of 117 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000505	Visual impairment
HP:0000543	Optic disc pallor
HP:0000572	Visual loss
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000670	Carious teeth
HP:0000684	Delayed eruption of teeth
HP:0000689	Dental malocclusion
HP:0000707	Abnormality of the nervous system
HP:0000772	Abnormal rib morphology
HP:0000774	Narrow chest
HP:0000944	Abnormal metaphysis morphology
HP:0000954	Single transverse palmar crease
HP:0000957	Cafe-au-lait spot
HP:0000967	Petechiae
HP:0000978	Bruising susceptibility
HP:0000980	Pallor
HP:0001010	Hypopigmentation of the skin
HP:0001272	Cerebellar atrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010002_107	Refractive error	6.000000e-18
GCST010481_10	Acute anterior uveitis in ankylosing spondylitis	1.000000e-06

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001847	Bone Diseases	C05.116
D003240	Connective Tissue Diseases	C17.300
D010022	Osteopetrosis	C05.116.099.708.702.678
C566933	Osteopetrosis, Autosomal Recessive 4 (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: other ic — ClC family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
DIDS	Channel blocker	4.4	pIC50
NS5818	Channel blocker	4.3	pIC50
NPPB	Channel blocker	3.8	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression, affects expression	3
Ozone	increases oxidation, increases expression, increases abundance, affects expression, affects cotreatment (+1 more)	3
sodium arsenite	affects expression, increases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases expression, increases abundance	2
apilimod	affects response to substance	2
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation, affects expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
cupric chloride	affects expression	1
coumarin	increases phosphorylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	increases expression	1
ginsenoside Rb1	decreases expression, decreases reaction	1
jinfukang	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
alpha-Chlorohydrin	decreases expression, decreases reaction	1
Atrazine	decreases expression	1
Vehicle Emissions	decreases methylation	1

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B1NG	Abcam HeLa CLCN7 KO	Cancer cell line	Female
CVCL_E0AB	Ubigene HeLa CLCN7 KO	Cancer cell line	Female
CVCL_E1DR	Ubigene U2OS CLCN7 KO	Cancer cell line	Female
CVCL_SJ17	HAP1 CLCN7 (-)	Cancer cell line	Male
CVCL_UM44	BIHi002-A	Induced pluripotent stem cell	Male
CVCL_UM45	BIHi002-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00004402	PHASE3	COMPLETED	Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT02584608	PHASE2	COMPLETED	Use of ACTIMMUNE in Patients With ADO2
NCT00638820	PHASE2	TERMINATED	Reduced Intensity AlloTransplant For Osteopetrosis
NCT00968864	PHASE2	TERMINATED	T-cell Depleted Alternative Donor Transplantation
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT02666768	PHASE2	COMPLETED	ACTIMMUNE in Intermediate Osteopetrosis
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT04525352	PHASE1	TERMINATED	A Trial to Evaluate Safety and Efficacy of RP-L401-0120 in Subjects With Infantile Malignant Osteopetrosis
NCT00145886	PHASE1	TERMINATED	rhPTH Therapy for Low Turnover Bone Fragility
NCT01093911	PHASE1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	PHASE1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	PHASE1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	PHASE1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	PHASE1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
NCT01166854	Not specified	RECRUITING	Characterization of Familial Myopathy and Paget Disease of Bone
NCT03527511	Not specified	COMPLETED	Effect of Active Vitamin D and Etelcalcetide on Human Osteoclasts in Patients With Chronic Kidney Disease