CLIC2

Summary

CLIC2 (CLIC family member 2, HGNC:2063) is a protein-coding gene on chromosome Xq28, encoding Chloride intracellular channel protein 2 (O15247). In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor.

This gene encodes a chloride intracellular channel protein. Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. This protein plays a role in inhibiting the function of ryanodine receptor 2. A mutation in this gene is the cause of an X-linked form of cognitive disability.

Source: NCBI Gene 1193 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome (Moderate, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 95 total — 1 likely-pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_001289

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2063
Approved symbol	CLIC2
Name	CLIC family member 2
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	XAP121, CLCNL2
Ensembl gene	ENSG00000155962
Ensembl biotype	protein_coding
OMIM	300138
Entrez	1193

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000321926, ENST00000369449, ENST00000465553, ENST00000491205, ENST00000948941

RefSeq mRNA: 1 — MANE Select: NM_001289 NM_001289

CCDS: CCDS14767

Canonical transcript exons

ENST00000369449 — 6 exons

Exon	Start	End
ENSE00001847718	155276211	155278064
ENSE00001890277	155334371	155334614
ENSE00003459873	155279962	155280068
ENSE00003518869	155298785	155298910
ENSE00003545471	155299036	155299145
ENSE00003567274	155279149	155279330

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 93.46.

FANTOM5 (CAGE): breadth broad, TPM avg 7.9582 / max 541.5667, expressed in 688 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201086	5.1044	630
201084	2.7854	451
201085	0.0684	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.46	gold quality
colonic epithelium	UBERON:0000397	90.39	gold quality
right lung	UBERON:0002167	90.03	gold quality
spleen	UBERON:0002106	89.22	gold quality
upper lobe of left lung	UBERON:0008952	89.22	gold quality
gall bladder	UBERON:0002110	89.17	gold quality
superficial temporal artery	UBERON:0001614	89.14	gold quality
upper lobe of lung	UBERON:0008948	89.08	gold quality
lymph node	UBERON:0000029	89.05	gold quality
left lobe of thyroid gland	UBERON:0001120	88.94	gold quality
thyroid gland	UBERON:0002046	88.62	gold quality
right lobe of thyroid gland	UBERON:0001119	88.43	gold quality
omental fat pad	UBERON:0010414	87.69	gold quality
peritoneum	UBERON:0002358	87.62	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.87	gold quality
lung	UBERON:0002048	86.78	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.74	gold quality
lower lobe of lung	UBERON:0008949	86.72	gold quality
tendon	UBERON:0000043	84.98	gold quality
rectum	UBERON:0001052	84.93	gold quality
vermiform appendix	UBERON:0001154	84.78	gold quality
skin of hip	UBERON:0001554	84.70	gold quality
pericardium	UBERON:0002407	84.59	gold quality
endocervix	UBERON:0000458	83.68	gold quality
adipose tissue	UBERON:0001013	83.64	gold quality
connective tissue	UBERON:0002384	83.40	gold quality
smooth muscle tissue	UBERON:0001135	83.35	gold quality
body of uterus	UBERON:0009853	83.10	gold quality
left ovary	UBERON:0002119	82.87	gold quality
mucosa of stomach	UBERON:0001199	82.52	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-86618	yes	404.20
E-MTAB-8142	yes	120.22
E-HCAD-11	yes	38.12
E-ANND-3	yes	22.63
E-MTAB-8498	yes	10.12
E-GEOD-135922	yes	9.68
E-MTAB-6678	yes	7.26
E-MTAB-5061	yes	6.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1, ZNF804A

miRNA regulators (miRDB)

76 targeting CLIC2, 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-4776-3P	100.00	68.73	1340
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-576-5P	99.84	70.46	2582

Literature-anchored findings (GeneRIF, showing 7)

• CLIC2 inhibited cardiac ryanodine receptor Ca2+ release channels in lipid bilayers when added to the cytoplasmic side of the channels and inhibited Ca2+ release from cardiac sarcoplasmic reticulum vesicles (PMID:15147738)
• CLIC2 forms pH-dependent chloride channels in vitro with higher channel activity at low pH levels and that the channels are subject to redox regulation (PMID:17945253)
• Human CLIC2 was crystallized in 2 different forms, in presence of GSSH. Form A displayed P2(1)2(1)2(1) symmetry, with unit-cell parameters a=44.0, b=74.7, c=79.8 A. Form B displayed P2(1) symmetry, with unit-cell parameters a=36.0, b=66.9, c=44.1 A. (PMID:18007051)
• crystal structure of soluble human CICL2 and implications for function (PMID:18186468)
• a vital role for the CLIC2 protein in maintaining normal cognitive function via its interaction with RyRs in the brain. (PMID:22814392)
• We have determined the crystal structure of soluble Clic2 from the euryhaline teleost fish Oreochromis mossambicus. Structural comparison of tilapia and human CLIC2 with other CLICs shows that these proteins are highly conserved. (PMID:29198705)
• Chloride intracellular channel protein 2 is secreted and inhibits MMP14 activity, while preventing tumor cell invasion and metastasis. (PMID:34229297)

Cross-species orthologs

33 orthologs

Organism	Symbol	Gene ID
danio_rerio	clic2	ENSDARG00000010625
rattus_norvegicus	Clic2	ENSRNOG00000000728
drosophila_melanogaster	GstD1	FBGN0001149
drosophila_melanogaster	GstD2	FBGN0010038
drosophila_melanogaster	GstD3	FBGN0010039
drosophila_melanogaster	GstD4	FBGN0010040
drosophila_melanogaster	GstD5	FBGN0010041
drosophila_melanogaster	GstD6	FBGN0010042
drosophila_melanogaster	GstD7	FBGN0010043
drosophila_melanogaster	GstD8	FBGN0010044
drosophila_melanogaster	GstE12	FBGN0027590
drosophila_melanogaster	Clic	FBGN0030529
drosophila_melanogaster	GstT3	FBGN0031117
drosophila_melanogaster	GstE13	FBGN0033381
drosophila_melanogaster	GstE1	FBGN0034335
drosophila_melanogaster	GstE11	FBGN0034354
drosophila_melanogaster	GstD9	FBGN0038020
drosophila_melanogaster	GstD10	FBGN0042206
drosophila_melanogaster	GstT1	FBGN0050000
drosophila_melanogaster	GstT2	FBGN0050005
drosophila_melanogaster	GstE9	FBGN0063491
drosophila_melanogaster	GstE8	FBGN0063492
drosophila_melanogaster	GstE7	FBGN0063493
drosophila_melanogaster	GstE6	FBGN0063494
drosophila_melanogaster	GstE5	FBGN0063495
drosophila_melanogaster	GstE4	FBGN0063496
drosophila_melanogaster	GstE3	FBGN0063497
drosophila_melanogaster	GstE2	FBGN0063498
drosophila_melanogaster	GstE10	FBGN0063499
caenorhabditis_elegans	exc-4	WBGENE00001365
caenorhabditis_elegans		WBGENE00001371
caenorhabditis_elegans	gst-43	WBGENE00001791
caenorhabditis_elegans		WBGENE00021817

Paralogs (14): GSTO2 (ENSG00000065621), GSTT2 (ENSG00000099984), GSTZ1 (ENSG00000100577), GDAP1 (ENSG00000104381), CLIC5 (ENSG00000112782), GDAP1L1 (ENSG00000124194), GSTT2B (ENSG00000133433), GSTO1 (ENSG00000148834), CLIC6 (ENSG00000159212), CLIC4 (ENSG00000169504), CLIC3 (ENSG00000169583), CLIC1 (ENSG00000213719), EEF1G (ENSG00000254772), GSTT4 (ENSG00000276950)

Protein

Protein identifiers

Chloride intracellular channel protein 2 — O15247 (reviewed: O15247)

Alternative names: Glutaredoxin-like oxidoreductase CLIC2, Glutaredoxin-like peroxidase CLIC2, XAP121

All UniProt accessions (2): O15247, A6PVS0

UniProt curated annotations — full annotation on UniProt →

Function. In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor. Displays weak glutathione peroxidase activity. Can insert into membranes and form chloride ion channels. Membrane insertion seems to be redox-regulated and may occur only under oxidizing conditions. Modulates the activity of RYR2 and inhibits calcium influx.

Subunit / interactions. Monomer. Interacts with TRAPPC2 and RYR2.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Expressed in adult and fetal brain, heart, skeletal muscle, liver, lung, and spleen. Detected in adult stomach and testis. Expressed in fetal thymus and kidney.

Activity regulation. The channel conductance is regulated by pH.

Domain organisation. Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as a chloride channel. The redox status of the active cysteine in Cys-X-X-Cys motif likely determines the capacity to adopt a soluble or membrane-inserted state. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion. The active G-site has a dithiol Cys-X-X-Cys motif which mediates glutathione-dependent redox catalysis.

Similarity. Belongs to the chloride channel CLIC family.

RefSeq proteins (1): NP_001280* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002946	CLIC	Family
IPR010987	Glutathione-S-Trfase_C-like	Domain
IPR030253	GST_C_CLIC-2	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR036282	Glutathione-S-Trfase_C_sf	Homologous_superfamily
IPR040079	Glutathione_S-Trfase	Family
IPR053823	CLIC_N	Domain

Pfam: PF13410, PF22441

Catalyzed reactions (Rhea), 3 shown:

• chloride(in) = chloride(out) (RHEA:29823)
• tert-butyl hydroperoxide + 2 glutathione = tert-butanol + glutathione disulfide + H2O (RHEA:69412)
• cumene hydroperoxide + 2 glutathione = 2-phenylpropan-2-ol + glutathione disulfide + H2O (RHEA:69651)

UniProt features (38 total): helix 11, strand 8, region of interest 5, turn 4, binding site 2, sequence conflict 2, chain 1, transmembrane region 1, disulfide bond 1, sequence variant 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2R4V	X-RAY DIFFRACTION	1.85
2R5G	X-RAY DIFFRACTION	1.86
2PER	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15247-F1	93.28	0.85

Functional residue map

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

Ligand- & substrate-binding residues (2): 227; 25

Disulfide bonds (1): 30–33

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels
R-HSA-5578775	Ion homeostasis

MSigDB gene sets: 285 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_REGULATION_OF_CARDIAC_MUSCLE_CONTRACTION_BY_REGULATION_OF_THE_RELEASE_OF_SEQUESTERED_CALCIUM_ION, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, GOBP_MONOATOMIC_CATION_TRANSPORT, GNF2_ANK1, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, GOBP_REGULATION_OF_STRIATED_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_CHLORIDE_TRANSPORT, GOBP_MUSCLE_CONTRACTION, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE

GO Biological Process (9): chloride transport (GO:0006821), signal transduction (GO:0007165), regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0010880), regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), negative regulation of ryanodine-sensitive calcium-release channel activity (GO:0060315), cellular oxidant detoxification (GO:0098869), chloride transmembrane transport (GO:1902476)

GO Molecular Function (4): glutathione peroxidase activity (GO:0004602), chloride channel activity (GO:0005254), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), chloride channel complex (GO:0034707), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Ion channel transport	1
Cardiac conduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
monoatomic anion transport	1
inorganic anion transport	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of release of sequestered calcium ion into cytosol	1
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of cardiac muscle contraction by calcium ion signaling	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
ryanodine-sensitive calcium-release channel activity	1
negative regulation of release of sequestered calcium ion into cytosol	1
regulation of ryanodine-sensitive calcium-release channel activity	1
negative regulation of calcium ion transmembrane transporter activity	1
cellular detoxification	1
chloride transport	1
monoatomic anion transmembrane transport	1
peroxidase activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
monoatomic ion channel complex	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

882 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLIC2	MAPK15	Q8TD08	828
CLIC2	PHC3	Q8NDX5	749
CLIC2	TRDN	Q13061	557
CLIC2	RAB39B	Q96DA2	520
CLIC2	ASPH	Q12797	474
CLIC2	TRAK2	O60296	473
CLIC2	EZR	P15311	458
CLIC2	PIN4	Q9Y237	444
CLIC2	CAV1	Q03135	437
CLIC2	RYR2	Q92736	431
CLIC2	MT-CO1	P00395	423
CLIC2	TMLHE	Q9NVH6	420
CLIC2	FAM229B	Q4G0N7	420
CLIC2	FUNDC2	Q9BWH2	420
CLIC2	VBP1	P61758	419

IntAct

15 interactions, top by confidence:

A	B	Type	Score
CLIC2	TPRN	psi-mi:“MI:0915”(physical association)	0.560
CLIC4	CLIC2	psi-mi:“MI:0914”(association)	0.530
CLIC5	CLIC2	psi-mi:“MI:0914”(association)	0.350
C15orf40	CLIC2	psi-mi:“MI:0914”(association)	0.350
RPL35	CLIC2	psi-mi:“MI:0914”(association)	0.350
RPP14	CLIC2	psi-mi:“MI:0914”(association)	0.350
TXNDC17	CLIC2	psi-mi:“MI:0914”(association)	0.350
SAP30	CLIC2	psi-mi:“MI:0914”(association)	0.350
CLIC2	TPRN	psi-mi:“MI:0914”(association)	0.350
FN1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLIC2	TPRN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): CLIC2 (Affinity Capture-MS), CLIC2 (Affinity Capture-MS), CLIC2 (Affinity Capture-MS), CLIC2 (Affinity Capture-MS), CLIC2 (Two-hybrid), TPRN (Two-hybrid), CLIC2 (Affinity Capture-MS), TPRN (Affinity Capture-MS), CLIC2 (Affinity Capture-MS), SBDS (Affinity Capture-MS), CLIC2 (Affinity Capture-MS), CLIC2 (Affinity Capture-MS), CLIC2 (Affinity Capture-MS), CLIC2 (Affinity Capture-MS), CLIC2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L5BUX8, A0A1U8QXK4, A0A1U9YI21, B5BP46, C8VQ63, D4Z909, M1W426, O00299, O04487, O15247, O45405, O74830, P12261, P21161, P26642, P30111, P34345, P36008, P40921, P42936, P43387, Q00717, Q4WB03, Q5E9B7, Q5M883, Q5R957, Q5Z627, Q6MG61, Q6NMS0, Q6YW46, Q8BXK9, Q8WQA4, Q91375, Q95MF9, Q9CA57, Q9CAS6, Q9EPT8, Q9FUM1, Q9FUS6, Q9FUT0

Diamond homologs: O00299, O15247, O95833, P35526, Q29238, Q5E9B7, Q5M883, Q5R957, Q6MG61, Q811Q2, Q8BHB9, Q8BXK9, Q95MF9, Q96NY7, Q9D7P7, Q9EPT8, Q9N2G5, Q9NZA1, Q9QYB1, Q9XSA7, Q9Y696, Q9Z0W7, Q9Z1Q5, O45405, Q9VY78, P81124, Q9FRL8, Q8WQA4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZNF804A	“down-regulates quantity by repression”	CLIC2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	37
Likely benign	8
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1808688	GRCh37/hg19 Xq28(chrX:154502832-154633634)x4	Likely pathogenic

SpliceAI

589 predictions. Top by Δscore:

Variant	Effect	Δscore
X:155278060:GCAAC:G	acceptor_gain	1.0000
X:155278061:CAAC:C	acceptor_gain	1.0000
X:155278061:CAACC:C	acceptor_gain	1.0000
X:155278062:AAC:A	acceptor_gain	1.0000
X:155278063:AC:A	acceptor_gain	1.0000
X:155278064:CC:C	acceptor_gain	1.0000
X:155278064:CCTA:C	acceptor_loss	1.0000
X:155278065:C:CA	acceptor_loss	1.0000
X:155278065:C:CC	acceptor_gain	1.0000
X:155278070:A:AC	acceptor_gain	1.0000
X:155278071:T:C	acceptor_gain	1.0000
X:155278071:T:TC	acceptor_gain	1.0000
X:155278072:T:C	acceptor_gain	1.0000
X:155278072:T:TC	acceptor_gain	1.0000
X:155278073:T:C	acceptor_gain	1.0000
X:155278073:T:TC	acceptor_gain	1.0000
X:155278076:C:CT	acceptor_gain	1.0000
X:155278077:A:T	acceptor_gain	1.0000
X:155279145:TTAC:T	donor_loss	1.0000
X:155279147:A:AC	donor_gain	1.0000
X:155279147:ACT:A	donor_loss	1.0000
X:155279148:C:CA	donor_gain	1.0000
X:155279148:CT:C	donor_gain	1.0000
X:155279148:CTT:C	donor_gain	1.0000
X:155279148:CTTT:C	donor_gain	1.0000
X:155279148:CTTTA:C	donor_gain	1.0000
X:155279326:AAAAT:A	acceptor_gain	1.0000
X:155279327:AAAT:A	acceptor_gain	1.0000
X:155279328:AAT:A	acceptor_gain	1.0000
X:155279329:AT:A	acceptor_gain	1.0000

AlphaMissense

1637 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:155277972:A:C	F225L	0.999
X:155277972:A:T	F225L	0.999
X:155277974:A:G	F225L	0.999
X:155279162:A:G	L190P	0.999
X:155279179:A:C	C184W	0.999
X:155279181:A:G	C184R	0.999
X:155279294:A:G	L146P	0.999
X:155280002:A:C	F120L	0.999
X:155280002:A:T	F120L	0.999
X:155280003:A:G	F120S	0.999
X:155280004:A:G	F120L	0.999
X:155280011:A:C	F117L	0.999
X:155280011:A:T	F117L	0.999
X:155280012:A:C	F117C	0.999
X:155280013:A:G	F117L	0.999
X:155298809:A:G	L90S	0.999
X:155298862:G:C	F72L	0.999
X:155298862:G:T	F72L	0.999
X:155298864:A:G	F72L	0.999
X:155298866:G:T	P71Q	0.999
X:155298867:G:A	P71S	0.999
X:155299062:A:C	F47L	0.999
X:155299062:A:T	F47L	0.999
X:155299063:A:G	F47S	0.999
X:155299064:A:G	F47L	0.999
X:155299074:T:A	K43N	0.999
X:155299074:T:G	K43N	0.999
X:155299075:T:A	K43I	0.999
X:155299092:G:C	F37L	0.999
X:155299092:G:T	F37L	0.999

dbSNP variants (sampled 300 via entrez): RS1000195252 (X:155275753 C>T), RS1000301853 (X:155285355 T>C), RS1000520478 (X:155310833 C>A), RS1000986289 (X:155328370 T>G), RS1001001769 (X:155319804 C>T), RS1001057917 (X:155310486 C>T), RS1001096762 (X:155319442 G>C,T), RS1001206498 (X:155306774 C>A), RS1001223601 (X:155292631 G>A,T), RS1001656943 (X:155323399 T>C), RS1001700165 (X:155306272 G>A), RS1001958712 (X:155323802 A>T), RS1002042885 (X:155334590 C>T), RS1002230923 (X:155293855 G>T), RS1002409743 (X:155282668 C>T)

Disease associations

OMIM: gene MIM:300138 | disease phenotypes: MIM:300886

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome	Moderate	X-linked
X-linked complex neurodevelopmental disorder	Disputed Evidence	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
X-linked complex neurodevelopmental disorder	Disputed	XL

Mondo (2): X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome (MONDO:0010473), X-linked complex neurodevelopmental disorder (MONDO:0100148)

Orphanet (1): X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome (Orphanet:324410)

HPO phenotypes

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

HPO	Term
HP:0000053	Macroorchidism
HP:0000232	Everted lower lip vermilion
HP:0000280	Coarse facial features
HP:0000303	Mandibular prognathia
HP:0000319	Smooth philtrum
HP:0000396	Overfolded helix
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0001172	Abnormal thumb morphology
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0001634	Mitral valve prolapse
HP:0001635	Congestive heart failure
HP:0001640	Cardiomegaly
HP:0001650	Aortic valve stenosis
HP:0001653	Mitral regurgitation
HP:0002187	Profound intellectual disability
HP:0002465	Poor speech
HP:0002510	Spastic tetraplegia
HP:0002540	Inability to walk
HP:0002751	Kyphoscoliosis
HP:0003376	Steppage gait
HP:0004749	Atrial flutter
HP:0005180	Tricuspid regurgitation
HP:0005280	Depressed nasal bridge
HP:0005781	Contractures of the large joints
HP:0006705	Abnormal atrioventricular valve morphology
HP:0010808	Protruding tongue

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases methylation, increases expression	3
bisphenol A	decreases expression, increases expression	2
Arsenic Trioxide	increases expression	2
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Demecolcine	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression, increases abundance	1
Vincristine	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	affects expression	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_YA41	IDG-HEK293T-CLIC2-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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