CAPN6

Summary

CAPN6 (calpain 6, HGNC:1483) is a protein-coding gene on chromosome Xq23, encoding Calpain-6 (Q9Y6Q1). Microtubule-stabilizing protein that may be involved in the regulation of microtubule dynamics and cytoskeletal organization.

Calpains are ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress. The protein encoded by this gene is highly expressed in the placenta. Its C-terminal region lacks any homology to the calmodulin-like domain of other calpains. The protein lacks critical active site residues and thus is suggested to be proteolytically inactive. The protein may play a role in tumor formation by inhibiting apoptosis and promoting angiogenesis.

Source: NCBI Gene 827 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 124 total — 5 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_014289

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1483
Approved symbol	CAPN6
Name	calpain 6
Location	Xq23
Locus type	gene with protein product
Status	Approved
Aliases	CAPNX, CalpM, CANPX
Ensembl gene	ENSG00000077274
Ensembl biotype	protein_coding
OMIM	300146
Entrez	827

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000324068, ENST00000932651

RefSeq mRNA: 1 — MANE Select: NM_014289 NM_014289

CCDS: CCDS14555

Canonical transcript exons

ENST00000324068 — 13 exons

Exon	Start	End
ENSE00000674897	111247368	111247504
ENSE00000674899	111247871	111247992
ENSE00000674900	111248569	111248771
ENSE00000674901	111248935	111249057
ENSE00000674902	111250917	111251103
ENSE00000674904	111251209	111251286
ENSE00000674906	111252307	111252499
ENSE00000830378	111263772	111263951
ENSE00001024279	111270371	111270483
ENSE00001245990	111245099	111246759
ENSE00003519137	111251549	111251742
ENSE00003583039	111253008	111253216
ENSE00003683031	111254272	111254403

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 99.12.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8623 / max 603.0906, expressed in 307 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200173	3.0692	286
200172	0.3893	123
200174	0.1325	62
200169	0.1206	21
200166	0.1012	20
200168	0.0224	8
200171	0.0156	8
200170	0.0079	2
200167	0.0037	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	99.12	gold quality
caput epididymis	UBERON:0004358	97.65	gold quality
tibia	UBERON:0000979	97.44	gold quality
corpus epididymis	UBERON:0004359	97.14	gold quality
placenta	UBERON:0001987	95.00	gold quality
seminal vesicle	UBERON:0000998	94.99	gold quality
cartilage tissue	UBERON:0002418	90.30	gold quality
gall bladder	UBERON:0002110	80.21	gold quality
body of uterus	UBERON:0009853	79.17	gold quality
rectum	UBERON:0001052	78.60	gold quality
parotid gland	UBERON:0001831	78.23	gold quality
renal medulla	UBERON:0000362	76.83	gold quality
smooth muscle tissue	UBERON:0001135	75.87	gold quality
vermiform appendix	UBERON:0001154	75.67	gold quality
colonic epithelium	UBERON:0000397	75.17	gold quality
decidua	UBERON:0002450	74.76	silver quality
stomach	UBERON:0000945	74.70	gold quality
caecum	UBERON:0001153	74.21	gold quality
epithelium of mammary gland	UBERON:0003244	73.88	gold quality
body of stomach	UBERON:0001161	73.26	gold quality
mammary duct	UBERON:0001765	73.18	gold quality
thoracic mammary gland	UBERON:0005200	72.96	gold quality
islet of Langerhans	UBERON:0000006	72.95	gold quality
mammary gland	UBERON:0001911	72.72	gold quality
metanephros cortex	UBERON:0010533	71.63	gold quality
saliva-secreting gland	UBERON:0001044	71.57	gold quality
pancreas	UBERON:0001264	71.53	gold quality
hindlimb stylopod muscle	UBERON:0004252	70.62	gold quality
body of pancreas	UBERON:0001150	70.54	gold quality
uterus	UBERON:0000995	70.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	76.54
E-MTAB-10042	yes	8.09
E-ANND-3	yes	4.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FOXD3, POU2F1

miRNA regulators (miRDB)

170 targeting CAPN6, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-124-3P	99.89	73.74	3043

Literature-anchored findings (GeneRIF, showing 9)

• results indicated that calpain 6 supported tumorigenesis by inhibiting apoptosis and facilitating angiogenesis. To our knowledge, this result is the first evidence implicating calpain 6 in tumorigenesis (PMID:18657900)
• syndecan-2 exerts its pro-apoptotic function through modulation of the endothelin-1/NFkappaB signaling and through downregulation of calpain-6. (PMID:21681744)
• High CAPN6 expression is associated with liver cancer. (PMID:26375440)
• CAPN6 promotes atherogenicity in inflamed macrophages by disturbing CWC22/EJC systems. (PMID:27525442)
• Non-proteolytic calpain-6 interacts with VEGFA and promotes angiogenesis by increasing VEGF secretion. (PMID:31673071)
• CAPN6 Regulates Uterine Leiomyoma Cell Proliferation and Apoptosis through the Rac1-Dependent Signaling Pathway. (PMID:32161009)
• The investigation of calpain in human placenta with fetal growth restriction. (PMID:32852077)
• A calpain-6/YAP axis in sarcoma stem cells that drives the outgrowth of tumors and metastases. (PMID:36153320)
• Advanced glycation end products promote the progression of chronic kidney diseases by targeting calpain 6. (PMID:37243758)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
mus_musculus	Capn6	ENSMUSG00000067276
rattus_norvegicus	Capn6	ENSRNOG00000004882
caenorhabditis_elegans		WBGENE00000542
caenorhabditis_elegans	clp-3	WBGENE00000544
caenorhabditis_elegans		WBGENE00000546
caenorhabditis_elegans		WBGENE00000547
caenorhabditis_elegans		WBGENE00006606
caenorhabditis_elegans	clp-8	WBGENE00009695
caenorhabditis_elegans	clpr-3	WBGENE00010417
caenorhabditis_elegans	clpr-1	WBGENE00012233
caenorhabditis_elegans	clpr-3	WBGENE00013184

Paralogs (20): CAPN1 (ENSG00000014216), SRI (ENSG00000075142), CAPN3 (ENSG00000092529), CAPN15 (ENSG00000103326), GCA (ENSG00000115271), ADGB (ENSG00000118492), CAPNS1 (ENSG00000126247), CAPN7 (ENSG00000131375), CAPN9 (ENSG00000135773), CAPN11 (ENSG00000137225), CAPN10 (ENSG00000142330), CAPN5 (ENSG00000149260), PEF1 (ENSG00000162517), CAPN2 (ENSG00000162909), CAPN13 (ENSG00000162949), CAPN12 (ENSG00000182472), CAPN8 (ENSG00000203697), CAPN14 (ENSG00000214711), PDCD6 (ENSG00000249915), CAPNS2 (ENSG00000256812)

Protein

Protein identifiers

Calpain-6 — Q9Y6Q1 (reviewed: Q9Y6Q1)

Alternative names: Calpain-like protease X-linked, Calpamodulin

All UniProt accessions (1): Q9Y6Q1

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-stabilizing protein that may be involved in the regulation of microtubule dynamics and cytoskeletal organization. May act as a regulator of RAC1 activity through interaction with ARHGEF2 to control lamellipodial formation and cell mobility. Does not seem to have protease activity as it has lost the active site residues.

Subunit / interactions. Interacts (via domain III) with microtubules. Interacts (via domain II) with ARHGEF2 (via the N-terminal zinc finger).

Subcellular location. Cytoplasm. Perinuclear region. Cytoskeleton. Spindle.

Tissue specificity. Expressed only in placenta.

Similarity. Belongs to the peptidase C2 family.

RefSeq proteins (1): NP_055104* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR001300	Peptidase_C2_calpain_cat	Domain
IPR022682	Calpain_domain_III	Domain
IPR022683	Calpain_III	Domain
IPR022684	Calpain_cysteine_protease	Family
IPR033883	C2_III	Domain
IPR033884	C2_Calpain	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036213	Calpain_III_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily

Pfam: PF00168, PF00648, PF01067

Enzyme classification (BRENDA):

• EC 3.4.22.B26 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (9 total): sequence variant 3, domain 2, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6Q1-F1	91.57	0.76

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 197 (showing top): RNGTGGGC_UNKNOWN, LEE_NEURAL_CREST_STEM_CELL_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, ATACCTC_MIR202, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, CCATCCA_MIR432, CEBPB_01, GTGCCTT_MIR506, MARTINEZ_RB1_TARGETS_UP, MARTINEZ_RB1_TARGETS_DN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY

GO Biological Process (3): microtubule bundle formation (GO:0001578), regulation of cytoskeleton organization (GO:0051493), proteolysis (GO:0006508)

GO Molecular Function (3): calcium-dependent cysteine-type endopeptidase activity (GO:0004198), microtubule binding (GO:0008017), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), spindle microtubule (GO:0005876), perinuclear region of cytoplasm (GO:0048471), spindle (GO:0005819), cytoskeleton (GO:0005856), microtubule (GO:0005874)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
microtubule cytoskeleton organization	1
cytoskeleton organization	1
regulation of organelle organization	1
protein metabolic process	1
cysteine-type endopeptidase activity	1
tubulin binding	1
binding	1
intracellular anatomical structure	1
spindle	1
microtubule	1
cytoplasm	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

1050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPN6	CAPNS1	P04632	826
CAPN6	ARHGEF2	Q92974	794
CAPN6	CALM1	P02593	568
CAPN6	CALML3	P27482	567
CAPN6	CALML6	Q8TD86	560
CAPN6	CALML4	Q96GE6	560
CAPN6	CALML5	Q9NZT1	560
CAPN6	CAST	P20810	521
CAPN6	NAV2	Q8IVL1	506
CAPN6	KIF5C	O60282	470
CAPN6	DCX	O43602	469
CAPN6	VGLL1	Q99990	445
CAPN6	XKR4	Q5GH76	437
CAPN6	TXLNG	Q9NUQ3	422
CAPN6	TRPC5	Q9UL62	403

IntAct

128 interactions, top by confidence:

A	B	Type	Score
ZBTB14	CAPN6	psi-mi:“MI:0915”(physical association)	0.560
CAPN6	UBA6	psi-mi:“MI:0914”(association)	0.530
CAPN6	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF11	CAPN6	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	CAPN6	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	PTPN13	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	TJP1	psi-mi:“MI:0407”(direct interaction)	0.440
CAPN6	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (33): SYNE2 (Affinity Capture-MS), BAZ1A (Affinity Capture-MS), CEP162 (Affinity Capture-MS), SUN1 (Affinity Capture-MS), LRFN4 (Affinity Capture-MS), UBA6 (Affinity Capture-MS), CHRAC1 (Affinity Capture-MS), FLNA (Affinity Capture-MS), HECTD1 (Affinity Capture-MS), BICD2 (Affinity Capture-MS), FAM101B (Affinity Capture-MS), GLDC (Affinity Capture-MS), ZBTB14 (Two-hybrid), CAPN6 (Proximity Label-MS), CAPN6 (Proximity Label-MS)

ESM2 similar proteins: A0A0G2JDV3, A0A2P1BRP3, A0A2P1BRQ0, A0ZSK3, A0ZSK4, A7RS11, A7T1N0, F4IDQ6, O08619, O35646, O81025, O88501, P27473, P32456, P49221, P52181, Q0GUM3, Q1LYL8, Q1MT80, Q2KTC2, Q3T9E4, Q53G44, Q5K651, Q5R9T9, Q62293, Q63663, Q66S25, Q69Z37, Q6DKF0, Q6ZN66, Q7EYV7, Q8BV66, Q8CBA2, Q8IVG5, Q8N8V2, Q8T773, Q8TCB0, Q91453, Q91Z40, Q96PP9

Diamond homologs: A6NHC0, A8MX76, G3V7W1, O08529, O08688, O14815, O15484, O23184, O35350, O35646, O35920, O75808, O88456, O88501, P00789, P04574, P04632, P05044, P06813, P06814, P06815, P07384, P13135, P16259, P17655, P20807, P27398, P27730, P28676, P30626, P34308, P35750, P43367, P43368, P51186, P97571, Q07009, Q11002, Q22036, Q27970

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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
Ras activation upon Ca2+ influx through NMDA receptor	5	50.1×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	47.7×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	47.7×	3e-06
Long-term potentiation	5	41.7×	4e-06
Assembly and cell surface presentation of NMDA receptors	9	40.1×	1e-10
Neurexins and neuroligins	10	34.5×	5e-11
Protein-protein interactions at synapses	6	28.0×	3e-06
RHOB GTPase cycle	5	13.5×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	69.2×	6e-14
protein localization to synapse	6	54.7×	1e-07
receptor clustering	7	52.0×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	41.3×	6e-08
negative regulation of ERK1 and ERK2 cascade	5	12.9×	1e-03
protein-containing complex assembly	9	12.2×	4e-06
cell-cell adhesion	10	12.1×	1e-06
protein localization to plasma membrane	7	9.1×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	44
Likely benign	1
Benign	12

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1710513	GRCh37/hg19 Xq21.1-24(chrX:76794355-119282836)x3	Pathogenic
2579273	GRCh38/hg38 Xq23(chrX:111250820-111333251)x1	Pathogenic
3246938	NC_000023.10:g.(?109919459)(110653626_?)del	Pathogenic
3766451	NM_014289.4(CAPN6):c.1088_1089del (p.Asp363fs)	Pathogenic
4279378	GRCh37/hg19 Xq23(chrX:110462490-110805640)x1	Pathogenic
4526876	NM_014289.4(CAPN6):c.860G>A (p.Gly287Glu)	Likely pathogenic

SpliceAI

1422 predictions. Top by Δscore:

Variant	Effect	Δscore
X:111246755:CAGAC:C	acceptor_gain	1.0000
X:111246756:AGAC:A	acceptor_gain	1.0000
X:111246757:GAC:G	acceptor_gain	1.0000
X:111246758:ACCT:A	acceptor_loss	1.0000
X:111246759:CCTG:C	acceptor_loss	1.0000
X:111246760:C:CC	acceptor_gain	1.0000
X:111246760:CTG:C	acceptor_loss	1.0000
X:111246761:T:A	acceptor_loss	1.0000
X:111247362:TCTTA:T	donor_loss	1.0000
X:111247363:CTTAC:C	donor_loss	1.0000
X:111247364:TTACC:T	donor_loss	1.0000
X:111247365:TACCT:T	donor_loss	1.0000
X:111247366:AC:A	donor_loss	1.0000
X:111247367:C:A	donor_loss	1.0000
X:111247500:TACAG:T	acceptor_gain	1.0000
X:111247501:ACAG:A	acceptor_gain	1.0000
X:111247502:CAG:C	acceptor_gain	1.0000
X:111247502:CAGC:C	acceptor_gain	1.0000
X:111247503:AG:A	acceptor_gain	1.0000
X:111247503:AGCTG:A	acceptor_loss	1.0000
X:111247504:GCTGG:G	acceptor_loss	1.0000
X:111247505:C:CC	acceptor_gain	1.0000
X:111247506:T:A	acceptor_loss	1.0000
X:111247846:T:A	donor_gain	1.0000
X:111247856:T:TA	donor_gain	1.0000
X:111247866:CTTA:C	donor_loss	1.0000
X:111247867:TTACT:T	donor_loss	1.0000
X:111247868:TA:T	donor_loss	1.0000
X:111247869:A:AC	donor_gain	1.0000
X:111247869:ACTTT:A	donor_gain	1.0000

AlphaMissense

4264 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:111248750:G:T	R435S	0.999
X:111248607:A:C	F482L	0.998
X:111248607:A:T	F482L	0.998
X:111248609:A:G	F482L	0.998
X:111248758:C:G	R432P	0.998
X:111248759:G:T	R432S	0.998
X:111250997:A:G	W360R	0.998
X:111250997:A:T	W360R	0.998
X:111263786:A:G	W51R	0.998
X:111263786:A:T	W51R	0.998
X:111247987:A:G	L497P	0.997
X:111248608:A:G	F482S	0.997
X:111249011:A:G	L402P	0.997
X:111249057:A:C	Y387D	0.997
X:111250932:G:C	F381L	0.997
X:111250932:G:T	F381L	0.997
X:111250934:A:G	F381L	0.997
X:111251600:C:G	R281P	0.997
X:111247912:A:T	V522D	0.996
X:111248641:G:C	P471R	0.996
X:111248641:G:T	P471Q	0.996
X:111248749:C:G	R435P	0.996
X:111248750:G:C	R435G	0.996
X:111250923:A:C	N384K	0.996
X:111250923:A:T	N384K	0.996
X:111250995:C:A	W360C	0.996
X:111250995:C:G	W360C	0.996
X:111251276:A:G	W302R	0.996
X:111251276:A:T	W302R	0.996
X:111251571:A:G	W291R	0.996

dbSNP variants (sampled 300 via entrez): RS1000035503 (X:111252231 C>A,T), RS1000272602 (X:111264211 C>T), RS1000286130 (X:111260643 G>A), RS1000299662 (X:111264715 A>AG), RS1000407370 (X:111254738 T>A), RS1000592555 (X:111269354 ATTTTTTTGTTTAT>A), RS1000638313 (X:111267370 C>T), RS1000741646 (X:111256857 A>AC), RS1000867001 (X:111246428 G>T), RS1001058965 (X:111269542 G>A), RS1001263574 (X:111253327 A>G), RS1001297487 (X:111246063 G>C,T), RS1001460129 (X:111252202 T>C), RS1001567815 (X:111262186 A>G), RS1001615405 (X:111252798 A>G)

Disease associations

OMIM: gene MIM:300146 | disease phenotypes: MIM:300067, MIM:190300

GenCC curated gene-disease

Mondo (3): prostate cancer (MONDO:0008315), lissencephaly type 1 due to doublecortin gene mutation (MONDO:0010239), essential tremor (MONDO:0003233)

Orphanet (3): Familial prostate cancer (Orphanet:1331), Lissencephaly type 1 due to doublecortin gene mutation (Orphanet:2148), NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D020329	Essential Tremor	C10.228.662.350
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	4
trichostatin A	affects cotreatment, decreases expression	3
Estradiol	decreases expression, affects cotreatment, increases expression	3
entinostat	affects cotreatment, decreases expression	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Progesterone	affects cotreatment, increases expression	2
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
ochratoxin A	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Amphotericin B	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	decreases expression, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer