CLCC1

Summary

CLCC1 (chloride channel CLIC like 1, HGNC:29675) is a protein-coding gene on chromosome 1p13.3, encoding Chloride channel CLIC-like protein 1 (Q96S66). Anion-selective channel with Ca(2+)-dependent and voltage-independent gating. It is a selective cancer dependency (DepMap: 19.9% of cell lines).

Enables chloride channel activity. Involved in endoplasmic reticulum calcium ion homeostasis. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum membrane contact site. Implicated in retinitis pigmentosa 32.

Source: NCBI Gene 23155 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 373 total
• Phenotypes (HPO): 11
• Cancer dependency (DepMap): dependent in 19.9% of screened cell lines
• MANE Select transcript: NM_001377458

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29675
Approved symbol	CLCC1
Name	chloride channel CLIC like 1
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MCLC
Ensembl gene	ENSG00000121940
Ensembl biotype	protein_coding
OMIM	617539
Entrez	23155

Gene structure

Transcript identifiers

Ensembl transcripts: 154 — 134 protein_coding, 13 nonsense_mediated_decay, 6 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000302500, ENST00000348264, ENST00000356970, ENST00000369968, ENST00000369969, ENST00000369970, ENST00000369976, ENST00000473062, ENST00000482889, ENST00000674527, ENST00000674561, ENST00000674849, ENST00000674992, ENST00000675001, ENST00000675018, ENST00000675128, ENST00000675247, ENST00000675451, ENST00000675508, ENST00000675571, ENST00000675584, ENST00000675650, ENST00000675654, ENST00000675790, ENST00000675956, ENST00000676059, ENST00000676306, ENST00000676391, ENST00000676392, ENST00000676454, ENST00000685014, ENST00000685104, ENST00000685497, ENST00000685540, ENST00000685628, ENST00000685791, ENST00000686078, ENST00000686434, ENST00000686576, ENST00000686776, ENST00000686817, ENST00000686821, ENST00000686961, ENST00000687099, ENST00000687134, ENST00000687226, ENST00000687328, ENST00000687449, ENST00000687591, ENST00000687646, ENST00000687675, ENST00000687734, ENST00000687865, ENST00000687998, ENST00000688070, ENST00000688168, ENST00000688285, ENST00000688298, ENST00000688610, ENST00000688778, ENST00000689103, ENST00000689189, ENST00000689351, ENST00000689359, ENST00000689479, ENST00000689991, ENST00000690509, ENST00000690707, ENST00000690756, ENST00000690781, ENST00000690874, ENST00000691342, ENST00000691513, ENST00000691556, ENST00000691731, ENST00000691777, ENST00000691876, ENST00000692184, ENST00000692342, ENST00000692404, ENST00000692511, ENST00000692584, ENST00000692732, ENST00000692775, ENST00000692795, ENST00000693089, ENST00000693336, ENST00000693673, ENST00000877074, ENST00000877075, ENST00000877076, ENST00000877077, ENST00000877078, ENST00000877079, ENST00000877080, ENST00000877081, ENST00000877082, ENST00000877083, ENST00000877084, ENST00000877085, ENST00000877086, ENST00000877087, ENST00000877088, ENST00000877089, ENST00000877090, ENST00000877091, ENST00000877092, ENST00000877093, ENST00000877094, ENST00000877095, ENST00000877096, ENST00000877097, ENST00000877098, ENST00000919820, ENST00000919821, ENST00000919822, ENST00000919823, ENST00000919824, ENST00000919825, ENST00000919826, ENST00000919827, ENST00000919828, ENST00000919829, ENST00000919830, ENST00000942010, ENST00000942011, ENST00000942012, ENST00000942013, ENST00000942014, ENST00000942015, ENST00000942016, ENST00000942017, ENST00000942018, ENST00000942019, ENST00000942020, ENST00000942021, ENST00000942022, ENST00000942023, ENST00000942024, ENST00000942025, ENST00000942026, ENST00000942027, ENST00000942028, ENST00000942029, ENST00000942030, ENST00000942031, ENST00000942032, ENST00000942033, ENST00000942034, ENST00000942035, ENST00000942036, ENST00000942037, ENST00000942038, ENST00000942039

RefSeq mRNA: 17 — MANE Select: NM_001377458 NM_001048210, NM_001278202, NM_001278203, NM_001377458, NM_001377459, NM_001377460, NM_001377461, NM_001377462, NM_001377463, NM_001377464, NM_001377465, NM_001377466, NM_001377467, NM_001377468, NM_001377469, NM_001377470, NM_015127

CCDS: CCDS41362, CCDS60214, CCDS60215, CCDS793, CCDS91013

Canonical transcript exons

ENST00000369969 — 13 exons

Exon	Start	End
ENSE00000826664	108934625	108934942
ENSE00000826665	108937077	108937418
ENSE00000912851	108947611	108947718
ENSE00000912853	108949820	108949921
ENSE00000958160	108950309	108950448
ENSE00001425240	108943836	108944057
ENSE00001451374	108962309	108962469
ENSE00003547625	108943475	108943615
ENSE00003613317	108940045	108940142
ENSE00003647002	108939636	108939782
ENSE00003673415	108941405	108941498
ENSE00003902594	108963361	108963484
ENSE00003903142	108929505	108932501

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.7284 / max 199.4382, expressed in 1818 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13662	23.7284	1818

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.06	gold quality
buccal mucosa cell	CL:0002336	96.51	gold quality
tendon	UBERON:0000043	96.44	gold quality
calcaneal tendon	UBERON:0003701	96.25	gold quality
medial globus pallidus	UBERON:0002477	92.96	gold quality
adrenal tissue	UBERON:0018303	92.03	gold quality
stromal cell of endometrium	CL:0002255	91.16	gold quality
body of pancreas	UBERON:0001150	90.72	gold quality
globus pallidus	UBERON:0001875	90.72	gold quality
islet of Langerhans	UBERON:0000006	90.11	gold quality
pancreas	UBERON:0001264	89.99	gold quality
muscle of leg	UBERON:0001383	89.71	gold quality
gastrocnemius	UBERON:0001388	89.53	gold quality
colonic epithelium	UBERON:0000397	89.18	gold quality
corpus callosum	UBERON:0002336	89.16	gold quality
parotid gland	UBERON:0001831	88.86	gold quality
biceps brachii	UBERON:0001507	88.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.28	gold quality
muscle organ	UBERON:0001630	87.71	gold quality
ventricular zone	UBERON:0003053	87.71	gold quality
endothelial cell	CL:0000115	87.61	gold quality
right coronary artery	UBERON:0001625	87.59	gold quality
endometrium	UBERON:0001295	87.46	gold quality
spinal cord	UBERON:0002240	87.30	gold quality
body of uterus	UBERON:0009853	87.22	gold quality
ascending aorta	UBERON:0001496	87.10	gold quality
thoracic aorta	UBERON:0001515	87.09	gold quality
body of stomach	UBERON:0001161	87.07	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.06
E-MTAB-6911	no	205.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

169 targeting CLCC1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-3910	99.95	71.13	2227

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 19.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Intracellular chloride transport by CLCC1 is a critical process in maintaining retinal integrity, and CLCC1 is crucial for survival and function of retinal cells. (PMID:30157172)
• Mutation and clinical analysis of the CLCC1 gene in amyotrophic lateral sclerosis patients from Central South China. (PMID:37916886)
• Unraveling the CLCC1 interactome: Impact of the Asp25Glu variant and its interaction with SigmaR1 at the Mitochondrial-Associated ER Membrane (MAM). (PMID:38621504)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Clcc1	ENSMUSG00000027884
rattus_norvegicus	Clcc1	ENSRNOG00000020360

Protein

Protein identifiers

Chloride channel CLIC-like protein 1 — Q96S66 (reviewed: Q96S66)

Alternative names: ER anion channel 1, Mid-1-related chloride channel protein

All UniProt accessions (19): A0A6Q8PEZ7, A0A6Q8PF11, A0A6Q8PF97, A0A6Q8PFF7, A0A6Q8PFH1, A0A6Q8PFT6, A0A6Q8PG14, A0A6Q8PG30, A0A6Q8PG68, A0A6Q8PG75, A0A6Q8PGA4, A0A6Q8PHQ1, A0A8I5KPC2, A0A8I5KQ17, A0A8I5KRC0, A0A8I5KXB0, A0A8I5KXZ8, Q96S66, Q5T1P5

UniProt curated annotations — full annotation on UniProt →

Function. Anion-selective channel with Ca(2+)-dependent and voltage-independent gating. Permeable to small monovalent anions with selectivity for bromide > chloride > nitrate > fluoride. Operates in the endoplasmic reticulum (ER) membrane where it mediates chloride efflux to compensate for the loss of positive charges from the ER lumen upon Ca(2+) release. Contributes to the maintenance of ER Ca(2+) pools and activation of unfolded protein response to prevent accumulation of misfolded proteins in the ER lumen. Particularly involved in ER homeostasis mechanisms underlying motor neurons and retinal photoreceptors survival.

Subunit / interactions. Homomultimers. Interacts with mitochondrial protein PIGBOS1 (via C-terminus); the interaction occurs at the mitochondria-associated endoplasmic reticulum (ER) membrane, a zone of contact between the ER and mitochondrial membranes, but does not appear to play a role in ER-mitochondria tethering and is not affected by ER stress. Interacts with CALR.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in the retina of the eye, with extensive expression in the lamina cribrosa, optic nerve, ganglion cell layer, inner nuclear layer, outer nuclear layer and retinal pigment epithelium.

Disease relevance. Retinitis pigmentosa 32 (RP32) [MIM:609913] A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP32 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Rare variants in CLCC1 may be associated with amyotrophic lateral sclerosis.

Activity regulation. Inhibited by ER lumenal Ca(2+).

Similarity. Belongs to the chloride channel MCLC family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96S66-1	1, hMCLC-1	yes
Q96S66-2	2, hMCLC-2
Q96S66-3	3, hMCLC-3
Q96S66-4	4, hMCLC-4

RefSeq proteins (17): NP_001041675, NP_001265131, NP_001265132, NP_001364387, NP_001364388, NP_001364389, NP_001364390, NP_001364391, NP_001364392, NP_001364393, NP_001364394, NP_001364395, NP_001364396, NP_001364397, NP_001364398, NP_001364399, NP_055942 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009231	Chloride_chnl_CLIC-like	Family

Pfam: PF05934

Catalyzed reactions (Rhea), 4 shown:

• chloride(in) = chloride(out) (RHEA:29823)
• nitrate(in) = nitrate(out) (RHEA:34923)
• bromide(in) = bromide(out) (RHEA:75383)
• fluoride(in) = fluoride(out) (RHEA:76159)

UniProt features (38 total): sequence variant 9, modified residue 6, mutagenesis site 5, topological domain 4, splice variant 3, transmembrane region 3, region of interest 2, compositionally biased region 2, site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96S66-F1	61.13	0.02

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): 25 (ca(2+)-mediated inhibition of channel activity); 181 (ca(2+)-mediated inhibition of channel activity)

Post-translational modifications (6): 438, 464, 482, 509, 524, 532

Mutagenesis-validated functional residues (5):

Position	Phenotype
152	does not affect ca(2+) binding; when associated with r-153.
153	does not affect ca(2+) binding; when associated with r-152.
175	decreases the affinity for ca(2+); when associated with r-176.
176	decreases the affinity for ca(2+); when associated with r-175.
181	impairs ca(2+) binding relieving ca(2+)-dependent inhibition of channel activity; when associated with r-25.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_CHLORIDE_TRANSPORT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_ENDOPLASMIC_RETICULUM_CALCIUM_ION_HOMEOSTASIS, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_ORGANELLE_MEMBRANE_CONTACT_SITE, GOBP_HOMEOSTATIC_PROCESS, GOCC_CHLORIDE_CHANNEL_COMPLEX, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOBP_CHEMICAL_HOMEOSTASIS

GO Biological Process (5): endoplasmic reticulum calcium ion homeostasis (GO:0032469), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), chloride transmembrane transport (GO:1902476)

GO Molecular Function (2): chloride channel activity (GO:0005254), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), chloride channel complex (GO:0034707), mitochondria-associated endoplasmic reticulum membrane contact site (GO:0044233)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endoplasmic reticulum	1
intracellular calcium ion homeostasis	1
transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
monoatomic ion channel complex	1
organelle membrane contact site	1

Protein interactions and networks

STRING

1158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLCC1	VPS39	Q96JC1	528
CLCC1	CFAP276	Q5T5A4	505
CLCC1	ERC1	Q8IUD2	499
CLCC1	STOML2	Q9UJZ1	482
CLCC1	AKNAD1	Q5T1N1	478
CLCC1	NRSN2	Q9GZP1	462
CLCC1	ZNF584	Q8IVC4	430
CLCC1	G3BP2	Q9UN86	430
CLCC1	GPSM2	P81274	402
CLCC1	PRR20A	P86496	398
CLCC1	NBPF4	Q96M43	397
CLCC1	KLK15	Q9H2R5	390
CLCC1	STXBP3	O00186	388
CLCC1	ZNF440	Q8IYI8	370
CLCC1	NUFIP2	Q7Z417	369

IntAct

129 interactions, top by confidence:

A	B	Type	Score
	VPS39	psi-mi:“MI:0914”(association)	0.960
	CLCC1	psi-mi:“MI:0914”(association)	0.870
CLCC1		psi-mi:“MI:0403”(colocalization)	0.870
	HMOX1	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
PIGBOS1	CLCC1	psi-mi:“MI:0915”(physical association)	0.630
PIGBOS1	CLCC1	psi-mi:“MI:2364”(proximity)	0.630
PIGBOS1	CLCC1	psi-mi:“MI:0403”(colocalization)	0.630
SPNS3	CLCC1	psi-mi:“MI:0915”(physical association)	0.620
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
TMA16	TNPO2	psi-mi:“MI:0914”(association)	0.530
CLCC1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
SEMA7A	SGPL1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
Klhl22	GLUD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (312): CLCC1 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), CLCC1 (Proximity Label-MS), CLCC1 (Proximity Label-MS), CLCC1 (Proximity Label-MS), CLCC1 (Proximity Label-MS), CLCC1 (Proximity Label-MS), CLCC1 (Proximity Label-MS), CLCC1 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Q3S9, A2VCV0, A9ULX8, E1BN97, F1NVK6, F6UF99, P28236, P79169, P79368, Q06220, Q09108, Q0P557, Q0VA42, Q1LZF8, Q28132, Q29030, Q2T9I9, Q3B7T8, Q3V0J1, Q5PQX1, Q5R6R3, Q5T5J6, Q5ZM60, Q640L3, Q640U0, Q66H73, Q6PAV5, Q6PG04, Q7ZX27, Q7ZXV6, Q8K4Q9, Q8N4S0, Q8TDY2, Q90314, Q90WN7, Q91892, Q921T2, Q95M19, Q95MD2, Q95N18

Diamond homologs: A0A2R8Q3S9, Q1LZF8, Q91892, Q96S66, Q99LI2, Q9WU61

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CLCC1	“up-regulates activity”	PIGBOS1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 149 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
Signaling by ERBB2 ECD mutants	5	35.4×	4e-05
GRB2 events in ERBB2 signaling	5	33.4×	4e-05
SHC1 events in ERBB2 signaling	5	25.0×	7e-05
Signaling by ERBB2 TMD/JMD mutants	5	25.0×	7e-05
Signaling by ERBB2 KD Mutants	5	22.3×	1e-04
Downstream signal transduction	5	20.0×	2e-04
DAP12 signaling	5	19.4×	2e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	8	8.2×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	5	16.3×	2e-03
cell surface receptor protein tyrosine kinase signaling pathway	11	14.8×	2e-07
cellular response to amino acid stimulus	5	11.9×	8e-03
insulin receptor signaling pathway	6	10.3×	4e-03
protein autophosphorylation	8	9.0×	8e-04
smoothened signaling pathway	6	8.4×	9e-03
transport across blood-brain barrier	6	8.3×	9e-03
positive regulation of MAPK cascade	11	6.9×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	208
Likely benign	125
Benign	19

Top pathogenic / likely-pathogenic (0)

SpliceAI

5126 predictions. Top by Δscore:

Variant	Effect	Δscore
1:108896862:A:AG	acceptor_gain	1.0000
1:108896863:G:GG	acceptor_gain	1.0000
1:108896863:GA:G	acceptor_gain	1.0000
1:108897480:T:A	acceptor_gain	1.0000
1:108897629:T:G	donor_loss	1.0000
1:108897954:TTTA:T	acceptor_loss	1.0000
1:108897955:TTAGG:T	acceptor_loss	1.0000
1:108897956:TAGG:T	acceptor_loss	1.0000
1:108897957:A:AT	acceptor_loss	1.0000
1:108898099:TGA:T	donor_gain	1.0000
1:108898099:TGAG:T	donor_loss	1.0000
1:108898100:GA:G	donor_gain	1.0000
1:108898100:GAG:G	donor_gain	1.0000
1:108898101:AG:A	donor_loss	1.0000
1:108898102:G:GG	donor_gain	1.0000
1:108898103:TGA:T	donor_loss	1.0000
1:108898104:GAGTA:G	donor_loss	1.0000
1:108898105:AGT:A	donor_loss	1.0000
1:108898878:GC:G	acceptor_gain	1.0000
1:108898993:AAGT:A	donor_loss	1.0000
1:108898995:G:T	donor_loss	1.0000
1:108898996:T:A	donor_loss	1.0000
1:108901785:T:TA	acceptor_gain	1.0000
1:108901786:GTA:G	acceptor_loss	1.0000
1:108901788:A:AG	acceptor_gain	1.0000
1:108901788:AG:A	acceptor_gain	1.0000
1:108901789:G:GG	acceptor_gain	1.0000
1:108901789:GG:G	acceptor_gain	1.0000
1:108901789:GGA:G	acceptor_gain	1.0000
1:108901789:GGAA:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000159660 (1:108936547 C>CTG), RS1000161167 (1:108942101 G>C), RS1000208067 (1:108948510 C>T), RS1000260267 (1:108948340 G>A), RS1000263693 (1:108930073 T>C), RS1000479224 (1:108961285 A>T), RS1000513330 (1:108942275 T>C), RS1000647495 (1:108954287 A>G), RS1000724156 (1:108930330 A>T), RS1000754271 (1:108947814 G>C), RS1000806742 (1:108947324 C>A,T), RS1000842201 (1:108965291 A>AT), RS1000852277 (1:108931264 T>A), RS1000910399 (1:108937892 A>T), RS1000956959 (1:108940958 TAAAA>T,TAAA,TAAAAA)

Disease associations

OMIM: gene MIM:617539 | disease phenotypes: MIM:604213, MIM:609913

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa	Limited	Autosomal recessive

Mondo (5): hearing loss disorder (MONDO:0005365), Chudley-McCullough syndrome (MONDO:0011411), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa 32 (MONDO:0012363), retinitis pigmentosa (MONDO:0019200)

Orphanet (3): Chudley-McCullough syndrome (Orphanet:314597), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

11 total (12 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000550	Undetectable electroretinogram
HP:0000580	Pigmentary retinopathy
HP:0000613	Photophobia
HP:0000662	Nyctalopia
HP:0007663	Reduced visual acuity
HP:0007737	Spicular pigmentation of the retina
HP:0007843	Attenuation of retinal blood vessels
HP:0030609	Photoreceptor layer loss on macular OCT
HP:0000556	Retinal dystrophy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001343_2	Fat distribution (HIV)	5.000000e-06
GCST001343_5	Fat distribution (HIV)	1.000000e-06
GCST001343_8	Fat distribution (HIV)	4.000000e-06
GCST005230_9	Recurrent major depressive disorder	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C535459	Chudley-Mccullough syndrome (supp.)
C563689	Retinitis Pigmentosa 32 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs168107	Toxicity	3	opioids	Nausea;Vomiting

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs168107	CLCC1	3	0.00	1	opioids

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression	3
Cyclosporine	increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
NSC668394	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Bilirubin	decreases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	affects cotreatment, increases expression, affects reaction	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Mustard Gas	decreases expression	1
Nicotine	increases expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]