RNLS

Summary

RNLS (renalase, FAD dependent amine oxidase, HGNC:25641) is a protein-coding gene on chromosome 10q23.31, encoding Renalase (Q5VYX0). Catalyzes the oxidation of the less abundant 1,2-dihydro-beta-NAD(P) and 1,6-dihydro-beta-NAD(P) to form beta-NAD(P)(+).

Enables several functions, including NADH binding activity; epinephrine binding activity; and monoamine oxidase activity. Involved in negative regulation of blood pressure and negative regulation of heart rate. Located in extracellular region. Implicated in essential hypertension and hypertension. Biomarker of end stage renal disease.

Source: NCBI Gene 55328 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract (Limited, GenCC)
• GWAS associations: 22
• Clinical variants (ClinVar): 105 total
• MANE Select transcript: NM_001031709

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25641
Approved symbol	RNLS
Name	renalase, FAD dependent amine oxidase
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11218, renalase
Ensembl gene	ENSG00000184719
Ensembl biotype	protein_coding
OMIM	609360
Entrez	55328

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000331772, ENST00000371947, ENST00000466945, ENST00000481793

RefSeq mRNA: 2 — MANE Select: NM_001031709 NM_001031709, NM_018363

CCDS: CCDS31239, CCDS7388

Canonical transcript exons

ENST00000331772 — 7 exons

Exon	Start	End
ENSE00001303608	88314466	88314641
ENSE00001321137	88284102	88285506
ENSE00001641933	88583073	88583318
ENSE00003539034	88582202	88582307
ENSE00003554623	88572903	88573061
ENSE00003556373	88581567	88581709
ENSE00003657202	88362552	88362725

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 93.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.4826 / max 60.2359, expressed in 1357 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110465	1.8459	1118
110462	0.6760	406
110464	0.5896	336
110463	0.1793	68
110460	0.1783	42
110461	0.0136	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.32	gold quality
right adrenal gland	UBERON:0001233	85.74	gold quality
left adrenal gland	UBERON:0001234	85.27	gold quality
right adrenal gland cortex	UBERON:0035827	84.76	gold quality
left adrenal gland cortex	UBERON:0035825	84.47	gold quality
adrenal gland	UBERON:0002369	83.80	gold quality
adrenal cortex	UBERON:0001235	83.39	gold quality
adrenal tissue	UBERON:0018303	81.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.12	gold quality
stromal cell of endometrium	CL:0002255	80.45	gold quality
parotid gland	UBERON:0001831	80.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.18	gold quality
gastrocnemius	UBERON:0001388	80.09	gold quality
heart left ventricle	UBERON:0002084	80.02	gold quality
muscle of leg	UBERON:0001383	80.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.83	gold quality
cardiac ventricle	UBERON:0002082	79.74	gold quality
rectum	UBERON:0001052	79.71	gold quality
heart	UBERON:0000948	78.99	gold quality
right atrium auricular region	UBERON:0006631	78.95	gold quality
cardiac atrium	UBERON:0002081	78.63	gold quality
germinal epithelium of ovary	UBERON:0001304	78.61	gold quality
pigmented layer of retina	UBERON:0001782	78.51	gold quality
adult mammalian kidney	UBERON:0000082	78.39	gold quality
left ventricle myocardium	UBERON:0006566	78.21	silver quality
islet of Langerhans	UBERON:0000006	78.08	gold quality
muscle organ	UBERON:0001630	77.24	gold quality
jejunal mucosa	UBERON:0000399	77.22	gold quality
esophagus squamous epithelium	UBERON:0006920	76.66	gold quality
gall bladder	UBERON:0002110	76.37	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-10	no	148.55
E-GEOD-36552	no	28.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, STAT3, ZNF148

miRNA regulators (miRDB)

49 targeting RNLS, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-19A-5P	99.36	66.93	1675

Literature-anchored findings (GeneRIF, showing 40)

• Renalase regulates cardiac function and blood pressure. (PMID:15841207)
• secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure (PMID:15841207)
• Renalase gene is a novel susceptibility gene for essential hypertension: a two-stage association study in northern Han Chinese population. (PMID:17216203)
• renalase pathway is a previously unrecognized mechanism for regulating circulating catecholamines & cardiac function, and blood pressure. Abnormalities in the renalase pathway are evident in animal models of chronic kidney disease and hypertension[review] (PMID:17565281)
• role in regulating blood pressure and cardiovascular function; abnormalities in the renalase pathway contribute to the heightened cardiovascular risks observed in patients with CKD. (PMID:19471322)
• Our identification of renalase, a soluble monoamine oxidase in the brain, highlights the possible existence of other pathways regulating monoamine neurotransmitter levels in the CNS. (PMID:20168325)
• The two recombinant renalase forms displayed the same molecular properties. They bind equimolar amounts of FAD and appear to be correctly folded by various criteria. (PMID:20302943)
• Studies in humans with resistant hypertension indicate that plasma renalase levels are inversely associated with systolic blood pressure–REVIEW (PMID:21424526)
• results are the first to suggest an association between renalase gene polymorphisms analysed and hypertension in dialysed patients. (PMID:21617193)
• Renalase adopts the p-hydroxybenzoate hydroxylase fold topology, comprising a Rossmann-fold-based flavin adenine dinucleotide (FAD)-binding domain and a putative substrate-binding domain. (PMID:21699903)
• The renalase gene polymorphism was associated with hypertension in type 2 diabetes patients. The most interesting result was a strong association of the rs10887800 polymorphism with stroke in patients with and without diabetes. (PMID:21964580)
• Renalase is highly elevated in kidney transplant recipients, predominantly dependent on kidney function, which deteriorates with time after kidney transplantation and age. (PMID:21996211)
• Renalase, highly elevated in heart transplant recipients, is predominantly dependent on kidney function, which deteriorates with time after heart transplantation and age. (PMID:22172866)
• polymorphisms of the renalase gene in hemodialysed patients were associated with hypertension [review] (PMID:22227817)
• A significant inverse correlation exists between serum renalase and residual kidney function. (PMID:22539018)
• Both before and after adjustment for sex, age and body mass index, the renalase polymorphisms did not show any effect on hypertension prevalence. (PMID:22812913)
• genome-wide association studies in European ancestry groups: Data suggest that alleles conferring susceptibility to type 1 diabetes [renalase (RNLS; rs10509540) and interleukin-2 (IL-2; rs2069763)] are associated with lower age-at-diagnosis/onset). (PMID:22891215)
• Renalase may play a critical role in reproduction and hormone regulation. (PMID:23271136)
• Renalase is elevated among heart transplant recipients and is predominantly dependent on renal function (PMID:23375328)
• Elevated level of circulating renalase in dialysis patients is related to kidney function and the sympathetic nervous system hyperactivity found in this population. (PMID:23530612)
• SNPs rs10887800 & rs2576178 were significantly associated with ischemic stroke with hypertension. The recessive model showed a strong association of rs2296545 with ischemic stroke patients in hypertension subgroups. (PMID:23564542)
• Our findings show that the polymorphism rs10887800 in the renalase gene is closely associated with severe intracranial cerebral atherosclerotic vascular stenosis in ischemic stroke patients of north Chinese Han origin. (PMID:24014100)
• Neither the oxidized nor the reduced form of renalase is able to catalyze anomerization, implying that the redox and anomerization chemistries are inextricably linked through a common intermediate. (PMID:24266457)
• Renalase promotes cell survival and protects against renal injury through the activation of intracellular signaling cascades, independent of its ability to metabolize catecholamines. (PMID:24511138)
• Serum levels of renalase are highly correlated with catecholamine and both serum renalase levels and renalase-catecholamine ratios are related to renal function (PMID:24590362)
• The allele A of rs2576178 may be a predisposing factor of coronary heart disease in hypertensive patients, and hypertensive patients with AA genotype are susceptible to develop coronary heart disease. (PMID:24821235)
• Renalase gene rs2296545 polymorphism is not important factor determining renal allograft function. (PMID:24923329)
• study is the first to present reference values of urine renalase excretion in a healthy pediatric population (PMID:25060760)
• Renalase transcript levels are associated with endogenous SP1, STAT3 and ZBP89 levels. (PMID:25295465)
• Renalase levels were higher in heart transplant recipients compared with healthy volunteers. (PMID:25380930)
• An association has been found between renalase (rs2296545) CC genotype and C allele and chronic kidney disease, along with significantly high serum epinephrine level. (PMID:25484193)
• the metabolic function of renalase is to oxidize isomeric NAD(P)H molecules to beta-NAD(P)(+). (PMID:25531177)
• Single nucleotide polymorphisms in nNOS, renalase, MTHFR, CELSR1 and XYLB genes were found significantly associated with ischemic stroke in Chinese patients. (PMID:25855559)
• Studies indicate definitive links between renalase catecholamine consumption and physiological responses. (PMID:25900362)
• This article demonstrates that renalase does not catalyze the oxidation of neurotransmitter catecholamines. (PMID:26049000)
• marked increase of glomerular renalase and its association with macrophages suggest that it might play an important role in disease progression of LN (PMID:26431044)
• the antihypertensive effect of renalase still remains a phenomenon with unclear biochemical mechanim(s) and functions of intracellular and extracellular (circulating) renalases obviously differ. (PMID:26716738)
• Data show that nhibition of renalase caused tumor cell apoptosis and cell cycle arrest. (PMID:26972355)
• The rs10887800 renalase gene polymorphism significantly increased the risk of coronary artery disease in hemodialyzed end-stage renal disease patients. (PMID:27023477)
• The development of preeclampsia in pregnant is accompanied by altered serum renalase levels. (PMID:27147460)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnls	ENSDARG00000012453
mus_musculus	Rnls	ENSMUSG00000071573
rattus_norvegicus	Rnls	ENSRNOG00000020705

Protein

Protein identifiers

Renalase — Q5VYX0 (reviewed: Q5VYX0)

Alternative names: Monoamine oxidase-C

All UniProt accessions (1): Q5VYX0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidation of the less abundant 1,2-dihydro-beta-NAD(P) and 1,6-dihydro-beta-NAD(P) to form beta-NAD(P)(+). The enzyme hormone is secreted by the kidney, and circulates in blood and modulates cardiac function and systemic blood pressure. Lowers blood pressure in vivo by decreasing cardiac contractility and heart rate and preventing a compensatory increase in peripheral vascular tone, suggesting a causal link to the increased plasma catecholamine and heightened cardiovascular risk. High concentrations of catecholamines activate plasma renalase and promotes its secretion and synthesis.

Subcellular location. Secreted.

Tissue specificity. Secreted into the blood by the kidney. Highly expressed in the kidney, expressed at lower level in heart, skeletal muscle and small intestine. Its plasma concentration is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects.

Similarity. Belongs to the renalase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VYX0-1	1	yes
Q5VYX0-2	2

RefSeq proteins (2): NP_001026879, NP_060833 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002937	Amino_oxidase	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR040174	RNLS	Family

Pfam: PF01593, PF13450

Enzyme classification (BRENDA):

• EC 1.6.3.5 — renalase (BRENDA: 6 organisms, 23 substrates, 10 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 4 shown:

• 1,2-dihydro-beta-NAD + O2 + H(+) = H2O2 + NAD(+) (RHEA:40395)
• 1,2-dihydro-beta-NADP + O2 + H(+) = H2O2 + NADP(+) (RHEA:40399)
• 1,6-dihydro-beta-NAD + O2 + H(+) = H2O2 + NAD(+) (RHEA:47996)
• 1,6-dihydro-beta-NADP + O2 + H(+) = H2O2 + NADP(+) (RHEA:48000)

UniProt features (43 total): strand 20, helix 13, binding site 3, turn 2, splice variant 2, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3QJ4	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VYX0-F1	96.79	0.94

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 (3): 12; 42; 61–62

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-196807	Nicotinate metabolism
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-197264

MSigDB gene sets: 100 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_NEGATIVE_REGULATION_OF_BLOOD_CIRCULATION, KOYAMA_SEMA3B_TARGETS_UP, GOBP_RESPONSE_TO_ISCHEMIA, GOBP_REGULATION_OF_HEART_RATE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_BLOOD_PRESSURE, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOBP_HEART_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_NAD_P_H, GOBP_RESPONSE_TO_EPINEPHRINE, VECCHI_GASTRIC_CANCER_EARLY_DN

GO Biological Process (6): response to ischemia (GO:0002931), negative regulation of heart rate (GO:0010459), negative regulation of blood pressure (GO:0045776), response to catecholamine (GO:0071869), response to epinephrine (GO:0071871), response to salt (GO:1902074)

GO Molecular Function (6): oxidoreductase activity, acting on NAD(P)H (GO:0016651), epinephrine binding (GO:0051379), NADH binding (GO:0070404), monoamine oxidase activity (GO:0097621), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to chemical	2
response to stress	1
regulation of heart rate	1
negative regulation of heart contraction	1
regulation of blood pressure	1
response to monoamine	1
response to oxygen-containing compound	1
oxidoreductase activity	1
hormone binding	1
cation binding	1
catecholamine binding	1
anion binding	1
NAD binding	1
oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor	1
binding	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNLS	MAOB	P27338	711
RNLS	MAOA	P21397	645
RNLS	ATP2B4	P23634	576
RNLS	MFSD6L	Q8IWD5	519
RNLS	AKR1E2	Q96JD6	492
RNLS	WDR87	Q6ZQQ6	487
RNLS	LIPJ	Q5W064	473
RNLS	PAOX	Q6QHF9	445
RNLS	SERTAD3	Q9UJW9	441
RNLS	GLIS3	Q8NEA6	439
RNLS	LYG1	Q8N1E2	433
RNLS	MRPS18A	Q9NVS2	433
RNLS	ARHGEF39	Q8N4T4	432
RNLS	ESR1	P03372	431
RNLS	INPP5A	Q14642	429

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RNLS	ATP2B4	psi-mi:“MI:0403”(colocalization)	0.460
RNLS	ATP2B4	psi-mi:“MI:0915”(physical association)	0.460
RNLS	ATP2B4	psi-mi:“MI:0915”(physical association)	0.400
MAST1	RNLS	psi-mi:“MI:0915”(physical association)	0.370
INSR	UBXN8	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): RNLS (Two-hybrid), RNLS (Affinity Capture-RNA), RNLS (Two-hybrid)

ESM2 similar proteins: A2AIG8, A6NFX1, O15315, O35083, O35719, O35790, O43502, O54783, O54804, O55229, O73884, P16442, P20417, P35790, P35821, P47802, Q01134, Q08DW9, Q27HK4, Q2TBS1, Q3T9M1, Q3U129, Q4R3I0, Q4R766, Q4R7M4, Q5E9H2, Q5E9T4, Q5SUV1, Q5SX19, Q5VYX0, Q6GV29, Q86XW9, Q8BVM4, Q8CIW5, Q8N2K0, Q8NBA8, Q8QGV6, Q8R2J9, Q8TCT0, Q924H5

Diamond homologs: A7RDN6, Q5U2W9, Q5VYX0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	14
Benign	27

Top pathogenic / likely-pathogenic (0)

SpliceAI

2901 predictions. Top by Δscore:

Variant	Effect	Δscore
10:88314642:C:CC	acceptor_gain	1.0000
10:88331697:T:A	donor_gain	1.0000
10:88362549:GA:G	donor_loss	1.0000
10:88362550:ACC:A	donor_loss	1.0000
10:88362551:C:T	donor_loss	1.0000
10:88362721:AATTA:A	acceptor_gain	1.0000
10:88362722:ATTA:A	acceptor_gain	1.0000
10:88362723:TTA:T	acceptor_gain	1.0000
10:88362724:TA:T	acceptor_gain	1.0000
10:88362726:C:CC	acceptor_gain	1.0000
10:88581604:T:TA	donor_gain	1.0000
10:88285503:TAACC:T	acceptor_loss	0.9900
10:88285504:AACC:A	acceptor_loss	0.9900
10:88285505:ACCT:A	acceptor_loss	0.9900
10:88285507:C:CG	acceptor_loss	0.9900
10:88285508:T:A	acceptor_loss	0.9900
10:88287716:A:T	acceptor_gain	0.9900
10:88288392:G:C	acceptor_gain	0.9900
10:88288392:G:GC	acceptor_gain	0.9900
10:88314637:TGACT:T	acceptor_gain	0.9900
10:88314640:CT:C	acceptor_gain	0.9900
10:88362550:A:AC	donor_gain	0.9900
10:88362551:C:CC	donor_gain	0.9900
10:88362722:ATTAC:A	acceptor_gain	0.9900
10:88362723:TTACT:T	acceptor_gain	0.9900
10:88362724:TACTG:T	acceptor_gain	0.9900
10:88362725:ACT:A	acceptor_gain	0.9900
10:88362726:CTGT:C	acceptor_gain	0.9900
10:88362727:T:A	acceptor_gain	0.9900
10:88362728:G:C	acceptor_gain	0.9900

AlphaMissense

2230 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:88362583:G:C	F223L	0.986
10:88362583:G:T	F223L	0.986
10:88362585:A:G	F223L	0.986
10:88573005:A:G	W142R	0.986
10:88573005:A:T	W142R	0.986
10:88314480:A:G	W288R	0.985
10:88314480:A:T	W288R	0.985
10:88362579:A:G	S225P	0.985
10:88572967:A:C	F154L	0.984
10:88572967:A:T	F154L	0.984
10:88572969:A:G	F154L	0.984
10:88314478:C:A	W288C	0.978
10:88314478:C:G	W288C	0.978
10:88362674:C:G	R193P	0.978
10:88362560:C:G	R231P	0.974
10:88362655:A:C	F199L	0.973
10:88362655:A:T	F199L	0.973
10:88362657:A:G	F199L	0.973
10:88314592:A:C	F250L	0.972
10:88314592:A:T	F250L	0.972
10:88314594:A:G	F250L	0.972
10:88362668:G:T	A195D	0.971
10:88362562:C:A	K230N	0.969
10:88362562:C:G	K230N	0.969
10:88362672:A:C	Y194D	0.969
10:88583149:G:C	S14R	0.969
10:88583149:G:T	S14R	0.969
10:88583151:T:G	S14R	0.969
10:88285426:A:C	F319L	0.968
10:88285426:A:T	F319L	0.968

dbSNP variants (sampled 300 via entrez): RS1000017616 (10:88414203 A>G), RS1000020488 (10:88501497 A>G), RS1000027976 (10:88284904 C>A), RS1000046677 (10:88537647 C>A,T), RS1000046874 (10:88557202 A>G), RS1000066789 (10:88427618 C>G), RS1000071162 (10:88185131 T>C), RS1000085441 (10:88188695 T>A), RS1000090046 (10:88278162 G>C), RS1000090838 (10:88508725 T>G), RS1000091901 (10:88462902 T>C,G), RS1000107692 (10:88298875 T>A,C), RS1000108159 (10:88497131 A>T), RS1000128225 (10:88371837 G>A,T), RS1000132294 (10:88240359 T>A)

Disease associations

OMIM: gene MIM:609360 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract	Limited	Autosomal recessive

Mondo (1): cataract (MONDO:0005129)

Orphanet (0):

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST000392_10	Type 1 diabetes	1.000000e-28
GCST002927_18	Mercury levels	3.000000e-06
GCST003090_2	Depressive and manic episodes in bipolar disorder	1.000000e-07
GCST006085_43	Prostate cancer	7.000000e-09
GCST006087_32	Familial lung adenocarcinoma	1.000000e-07
GCST006135_1	Cortical amyloid beta load	8.000000e-07
GCST006135_11	Cortical amyloid beta load	7.000000e-07
GCST006291_41	Spherical equivalent or myopia (age of diagnosis)	5.000000e-12
GCST006815_2	End stage renal disease in APOL1 risk genotype-negative individuals	3.000000e-06
GCST007096_92	Pulse pressure	2.000000e-09
GCST007495_2	Estimated glomerular filtration rate in coronary artery disease and impaired kidney function	6.000000e-08
GCST008362_119	Birth weight	2.000000e-08
GCST008839_135	Height	1.000000e-06
GCST009875_10	Type 1 diabetes	7.000000e-12
GCST009916_4	Type 1 diabetes	1.000000e-06
GCST010002_295	Refractive error	5.000000e-32
GCST010653_44	Thyroid stimulating hormone levels	1.000000e-13
GCST011011_58	Youthful appearance (self-reported)	2.000000e-08
GCST90002383_492	Hematocrit	3.000000e-11
GCST90002384_271	Hemoglobin	1.000000e-11
GCST90011898_77	Alanine aminotransferase levels	6.000000e-09
GCST90016669_5	Pancreas volume	2.000000e-09

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007704	depressive episode measurement
EFO:0007705	manic episode measurement
EFO:0006953	family history of lung cancer
EFO:0007707	cerebral amyloid deposition measurement
EFO:0004847	age at onset
EFO:0005763	pulse pressure measurement
EFO:0004344	birth weight
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002386	Cataract	C11.510.245

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, decreases expression, affects expression	6
Benzo(a)pyrene	decreases expression, decreases methylation	3
Cadmium	increases abundance, decreases expression	2
Testosterone	increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
arsenite	decreases expression	1
nickel sulfate	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Mustard Gas	decreases expression	1
Phthalic Acids	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00273221	PHASE4	UNKNOWN	Combined Phacotube vs Phacotrabeculectomy:A Randomized Controlled Trial
NCT00312299	PHASE4	COMPLETED	Posterior Capsule Opacification Study
NCT00345046	PHASE4	COMPLETED	A Comparison of Three Different Formulations of Prednisolone Acetate 1%
NCT00347243	PHASE4	COMPLETED	Wavefront Analisys and Contrast Sensitivity of Spherical and Aspherical Intraocular Lenses
NCT00347503	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients
NCT00348244	PHASE4	COMPLETED	Ketorolac vs. Steroid in the Prevention of CME
NCT00348270	PHASE4	COMPLETED	Comparison of the Quality of Vision Provided by AMO Tecnis Z9000 and Alcon Laboratories MA60 Acrysof Posterior Chamber Intraocular Lenses
NCT00348582	PHASE4	COMPLETED	Acular LS vs. Nevanac in Post op Inflammation Following Cataract Surgery
NCT00348621	PHASE4	COMPLETED	A Study of Interventions to Reduce Disability From Visual Loss in Nursing Home Residents
NCT00349583	PHASE4	COMPLETED	Efficacy of Topical Cyclosporine Versus Tears for Improving Visual Outcomes Following Multifocal IOL Implantation
NCT00355446	PHASE4	COMPLETED	Bioavailability of Bimatoprost Ophthalmic Solution in Human Aqueous.
NCT00386438	PHASE4	COMPLETED	Efficacy of Honan Balloon in Intraocular Pressure Reduction Before Phacoemulsification
NCT00392275	PHASE4	COMPLETED	Penetrance of Third Generation Fluoroquinolones in Eyes With Functioning Filtering Blebs
NCT00428363	PHASE4	COMPLETED	Effect of Optic Edge Design in a Silicone Intraocular Lens on Posterior Capsule Opacification
NCT00449267	PHASE4	COMPLETED	Aurolab Hydrophobic Foldable Intraocular Lens Study
NCT00459303	PHASE4	COMPLETED	Comparison of Functional Vision Provided by AMO Tecnis Z9000 and Alcon SA60AT Acrysof
NCT00469690	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients: Trough Drug Effects
NCT00576485	PHASE4	COMPLETED	Spherical Aberration and Contrast Sensitivity in IOLs
NCT00612729	PHASE4	COMPLETED	Light Filters in Intraocular Lenses (IOLs) and Its Influence on Colour and Contrast Vision.
NCT00612781	PHASE4	COMPLETED	Yellow Versus White Study
NCT00630019	PHASE4	COMPLETED	Ocular Tissue Levels of 1.5% Levofloxacin Ophthalmic Solution Compared to an Active Comparator
NCT00673803	PHASE4	COMPLETED	Influence of Two Different Preloaded Intraocular Lens (IOLs) on Posterior Capsule Opacification
NCT00684138	PHASE4	COMPLETED	ACRYSOF® ReSTOR® Aspheric +3.0 D Add Power Intraocular Lens (IOL)
NCT00698724	PHASE4	COMPLETED	Comparing Optical Coherence Tomography (OCT) and Visual Acuity Outcomes in Subjects Undergoing Cataract Surgery, Who Receive Xibrom Ophthalmic Solution and Standard Presurgical Care vs. Xibrom Ophthalmic Solution Plus Prednisolone Acetate 1% and Standard Presurgical Care
NCT00710905	PHASE4	TERMINATED	Visual Function With Contralateral AcrySof® ReSTOR® Aspheric SN6AD1 and SN6AD3
NCT00710931	PHASE4	COMPLETED	Visual Function With Bilateral AcrySof® ReSTOR® Aspheric SN6AD1
NCT00711347	PHASE4	COMPLETED	Intraoperative Floppy Iris Syndrome
NCT00712244	PHASE4	COMPLETED	DisCoVisc Versus DuoVisc, Healon5 and AmVisc Plus
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00719732	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof ReSTOR Aspheric +3
NCT00721253	PHASE4	COMPLETED	Visual Outcomes of Subjects Bilaterally Implanted With ReSTOR Aspheric +4 vs. Tecnis or Acri.LISA
NCT00731640	PHASE4	COMPLETED	Contralateral ReSTOR / Monofocal or Phakic Eye
NCT00732030	PHASE4	COMPLETED	Low Cylinder Toric
NCT00758199	PHASE4	COMPLETED	Determination of Optimum Duration of Treatment With Bromfenac (Xibrom) Eyedrops Following Cataract Surgery
NCT00760058	PHASE4	WITHDRAWN	Visual Outcome and Visual Quality After Bilateral Implantation of the AcrySof® IQ IOL Compared to MI60® and Tecnis® IOL
NCT00760487	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof® Toric Natural Intraocular Lens
NCT00761488	PHASE4	WITHDRAWN	Recommendations for Monitoring Clinical Experience Following Implantation of the AcrySof® Toric
NCT00763360	PHASE4	COMPLETED	To Compare the Ability of DiscoVisc® OVD to Protect the Corneal Endothelium and Maintain Anterior Chamber Space With Healon® and Amvisc® PLUS During Cataract Surgery.
NCT00786370	PHASE4	COMPLETED	Dexmedetomidine vs. Propofol for Cataract Surgery
NCT00786565	PHASE4	COMPLETED	Clinical Evaluation of a New Aspheric Intraocular Lens.