ZNF469

Summary

ZNF469 (zinc finger protein 469, HGNC:23216) is a protein-coding gene on chromosome 16q24.2, encoding Zinc finger protein 469 (Q96JG9). May be involved in transcriptional regulation.

This gene encodes a zinc-finger protein. Low-percent homology to certain collagens suggests that it may function as a transcription factor or extra-nuclear regulator factor for the synthesis or organization of collagen fibers. Mutations in this gene cause brittle cornea syndrome.

Source: NCBI Gene 84627 — RefSeq curated summary.

At a glance

• Gene–disease (curated): brittle cornea syndrome 1 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 32
• Clinical variants (ClinVar): 5,625 total — 163 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 49
• MANE Select transcript: NM_001367624

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23216
Approved symbol	ZNF469
Name	zinc finger protein 469
Location	16q24.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1858, Zfp469
Ensembl gene	ENSG00000225614
Ensembl biotype	protein_coding
OMIM	612078
Entrez	84627

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000437464, ENST00000565624

RefSeq mRNA: 1 — MANE Select: NM_001367624 NM_001367624

CCDS: CCDS92205

Canonical transcript exons

ENST00000565624 — 3 exons

Exon	Start	End
ENSE00002581233	88427345	88440753
ENSE00003858955	88424807	88424871
ENSE00003882229	88382959	88383254

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 91.30.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2879 / max 43.9610, expressed in 788 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155523	1.6609	686
155522	0.6270	347

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	91.30	gold quality
upper arm skin	UBERON:0004263	89.63	gold quality
cartilage tissue	UBERON:0002418	88.50	gold quality
vena cava	UBERON:0004087	84.84	silver quality
epithelial cell of pancreas	CL:0000083	84.71	silver quality
kidney epithelium	UBERON:0004819	84.18	gold quality
heart right ventricle	UBERON:0002080	83.43	silver quality
left ventricle myocardium	UBERON:0006566	83.22	gold quality
saphenous vein	UBERON:0007318	82.99	gold quality
cardiac muscle of right atrium	UBERON:0003379	82.86	gold quality
cardia of stomach	UBERON:0001162	82.39	silver quality
subthalamic nucleus	UBERON:0001906	82.26	gold quality
pons	UBERON:0000988	82.25	gold quality
ventral tegmental area	UBERON:0002691	82.19	gold quality
trachea	UBERON:0003126	82.18	silver quality
pericardium	UBERON:0002407	81.94	gold quality
medulla oblongata	UBERON:0001896	81.79	gold quality
body of tongue	UBERON:0011876	81.65	silver quality
pancreatic ductal cell	CL:0002079	81.52	silver quality
dorsal plus ventral thalamus	UBERON:0001897	81.35	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	81.26	gold quality
nipple	UBERON:0002030	81.17	silver quality
pharyngeal mucosa	UBERON:0000355	81.13	silver quality
cerebellar vermis	UBERON:0004720	81.03	gold quality
superior vestibular nucleus	UBERON:0007227	80.88	gold quality
inferior vagus X ganglion	UBERON:0005363	80.86	silver quality
lateral nuclear group of thalamus	UBERON:0002736	79.97	gold quality
superior surface of tongue	UBERON:0007371	79.66	silver quality
layer of synovial tissue	UBERON:0007616	79.50	silver quality
substantia nigra pars compacta	UBERON:0001965	78.97	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.71

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 23)

• 30% homology to a number of collagens suggests that ZNF469 could act as a transcription factor involved in the synthesis and/or organization of collagen fibers. (PMID:18452888)
• The results confirm that BCS (brittle cornea syndrome) is associated with mutations in ZNF469. (PMID:19661234)
• ZNF469 mutation may predispose to childhood blue sclera without BCS only in certain individuals, depending on other genetic and/or environmental conditions (PMID:20938016)
• ZNF469 and PRDM5, two genes that when mutated cause brittle cornea syndrome, participate in the same regulatory pathway. (PMID:21664999)
• We document a novel homozygous ZNF469 mutation in an adult with corneal fragility but lacking clinical evidence for extraocular manifestations. (PMID:22486320)
• Mutations in COL5A1 gene is associated with central corneal thickness in glaucoma. (PMID:22814818)
• A novel homozygous 14 bp duplication in exon 2 of ZNF469 (c.8817_8830dup) was uncovered by direct sequencing (PMID:23010198)
• ZNF469 frequently mutated in the brittle cornea syndrome (BCS) is a single exon gene possibly regulating the expression of several extracellular matrix components. (PMID:23680354)
• Results show that enrichment of rare potentially pathogenic alleles in ZNF469 in 12.5% of keratoconus patients represents a significant mutational load and highlights ZNF469 as the most significant genetic factor responsible for keratoconus identified. (PMID:24895405)
• Rare missense mutations in ZNF469, predicted to be pathogenic, occurred heterozygously, at a frequency of 23% in a keratoconus population. (PMID:25097247)
• The presence of heterozygous loss-of-function alleles in the ZNF469 gene did not cause keratoconus in the individuals examined. (PMID:25564447)
• we have not found a significant enrichment of sequence variants in ZNF469 in Polish patients with keratoconus (KTCN). High prevalence of ZNF469 variants identified in our KTCN group is typical for a common genetic variation observed in general population. (PMID:26806788)
• ZNF469 has a pathogenic role in Chinese patients with keratoconus. (PMID:28484309)
• New detected ZNF 469 P873T and Q2188H heterozygote coding variants in isolated advance keratoconus patients may be associated with the disease pathogenesis. (PMID:28622062)
• genotype frequencies did not differ between the sporadic or familial keratoconus cases (PMID:29187250)
• Rare variants in ZNF469 do not contribute to keratoconus susceptibility and do not account for the association at rs9938149. (PMID:29228253)
• Linc-ZNF469-3 promotes lung metastasis of TNBC through miR-574-5p-ZEB1 signaling axis. (PMID:29755127)
• This is the first report of a ZNF469 homozygous mutation causing a Brittle cornea syndrome phenotype in a consanguineous Pakistani family. (PMID:30865045)
• CXL may be associated with the development of corneal perforation in particular at-risk individuals with keratoconus. Identifying clinical and genetic risk factors, including screening of ZNF469 and PRDM5, may be useful in the prevention of significant complications after CXL. (PMID:31107761)
• More than meets the eye: Expanding and reviewing the clinical and mutational spectrum of brittle cornea syndrome. (PMID:33739556)
• New ZNF469 Mutations in Spanish Siblings With Brittle Cornea Syndrome. (PMID:37098112)
• Genetic variants in the FOXO1 and ZNF469 genes are associated with keratoconus in Sweden: a case-control study. (PMID:38267912)
• ZNF469 is a profibrotic regulator of extracellular matrix in hepatic stellate cells. (PMID:38704698)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp469	ENSMUSG00000043903
rattus_norvegicus	Zfp469	ENSRNOG00000084845

Protein

Protein identifiers

Zinc finger protein 469 — Q96JG9 (reviewed: Q96JG9)

All UniProt accessions (2): A0AAA9X9E9, Q96JG9

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Tissue specificity. Detected in cornea, sclera, skin fibroblasts and striated muscle.

Disease relevance. Brittle cornea syndrome 1 (BCS1) [MIM:229200] An autosomal recessive disorder characterized by extreme corneal thinning resulting in corneal rupture after minor trauma, blue sclerae, keratoconus or keratoglobus, hyperelasticity of the skin, and hypermobility of the joints. It shares some features with, but is much less severe than, the ocular form of Ehlers-Danlos syndrome (EDS6). The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_001354553* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR039270	ZNF469	Family

Pfam: PF00096

UniProt features (79 total): compositionally biased region 43, region of interest 18, sequence variant 12, zinc finger region 5, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q96JG9 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 166 (showing top): GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP, CHICAS_RB1_TARGETS_CONFLUENT, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, PLASARI_TGFB1_TARGETS_10HR_UP, DELACROIX_RAR_TARGETS_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, NFKBIA_TARGET_GENES, MIR548AJ_3P_MIR548X_3P, MIR548AE_3P_MIR548AQ_3P, MIR548AH_3P_MIR548AM_3P, MIR548J_3P, MIR23A_3P_MIR23B_3P, MIR23C

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of extracellular matrix organization (GO:1903053)

GO Molecular Function (4): DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
extracellular matrix organization	1
regulation of cellular component organization	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF469	CHST14	Q8NCH0	979
ZNF469	PLOD1	Q02809	800
ZNF469	COL5A1	P20908	692
ZNF469	PLOD3	O60568	671
ZNF469	PLOD2	O00469	651
ZNF469	VSX1	Q9NZR4	629
ZNF469	FNDC3B	Q53EP0	621
ZNF469	FKBP14	Q9NWM8	605
ZNF469	MPDZ	O75970	592
ZNF469	COL8A2	P25067	583
ZNF469	B4GALT7	Q9UBV7	575
ZNF469	LNX1	Q8TBB1	575
ZNF469	BANP	Q8N9N5	571
ZNF469	RAB3GAP1	Q15042	550
ZNF469	SLC39A13	Q96H72	540

IntAct

7 interactions, top by confidence:

A	B	Type	Score
MAP1LC3B	ZNF469	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF469	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
ZNF469	H2BC13	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): ZNF469 (Affinity Capture-MS), ZNF469 (Affinity Capture-MS), ZNF469 (Affinity Capture-RNA), HIST1H2BL (Proximity Label-MS), ZNF469 (Proximity Label-MS), ZNF469 (Affinity Capture-MS), ZNF469 (Affinity Capture-MS), ZNF469 (Affinity Capture-MS), ZNF469 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0J9YXV3, A0A172M4N0, A2VE23, A5PL33, C7EMF5, E7EW31, F1NSM7, I3L273, O15027, O48582, O55189, O55196, O97939, P0C671, P0DV77, P14138, Q14D33, Q1XI13, Q28989, Q3B7M4, Q4R729, Q5R7U0, Q5SWP3, Q62840, Q63003, Q6E0U4, Q6H236, Q6NUN9, Q6UXA7, Q7Z2K8, Q86UU5, Q8BM15, Q8K4E0, Q8K4L6, Q8N1P7, Q8N3D4, Q96D09, Q96JG9, Q9BGL9, Q9D7G9

Diamond homologs: A1XSY8, A2A884, A2ANX9, A7Y7X5, B0X9H6, E9PZZ1, E9Q6W4, G5EBU4, J9VX63, O60315, O62836, O75362, O77027, O77459, O95863, P03001, P08048, P08152, P10925, P11161, P13360, P15822, P17010, P17012, P20662, P25932, P26633, P28166, P31508, P31509, P31629, P36197, P39768, P51774, P52739, P60319, P80944, Q00453, Q00900, Q01611

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

5625 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	163
Likely pathogenic	26
Uncertain significance	2475
Likely benign	2308
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
126931	NM_001367624.2(ZNF469):c.77G>C (p.Ser26Thr)	Pathogenic
126939	NM_001367624.2(ZNF469):c.2699C>G (p.Pro900Arg)	Pathogenic
126942	NM_001367624.2(ZNF469):c.337G>A (p.Glu113Lys)	Pathogenic
126944	NM_001367624.2(ZNF469):c.5681A>T (p.Gln1894Leu)	Pathogenic
1364049	NM_001367624.2(ZNF469):c.5661_5668del (p.His1888fs)	Pathogenic
1376500	NM_001367624.2(ZNF469):c.2440_2444del (p.Thr814fs)	Pathogenic
1420003	NM_001367624.2(ZNF469):c.1963dup (p.His655fs)	Pathogenic
1453084	NM_001367624.2(ZNF469):c.460dup (p.Gln154fs)	Pathogenic
1454416	NM_001367624.2(ZNF469):c.9243_9262dup (p.Gln3088fs)	Pathogenic
1683288	NM_001367624.2(ZNF469):c.8428del (p.Ala2810fs)	Pathogenic
1753065	NM_001367624.2(ZNF469):c.6445C>T (p.Gln2149Ter)	Pathogenic
1787451	NM_001367624.2(ZNF469):c.2193del (p.Thr732fs)	Pathogenic
1960318	NM_001367624.2(ZNF469):c.8992C>T (p.Arg2998Ter)	Pathogenic
1993739	NM_001367624.2(ZNF469):c.5948G>A (p.Trp1983Ter)	Pathogenic
2008901	NM_001367624.2(ZNF469):c.2177_2180del (p.Gln726fs)	Pathogenic
2012854	NM_001367624.2(ZNF469):c.3067del (p.Arg1023fs)	Pathogenic
2027646	NM_001367624.2(ZNF469):c.3526C>T (p.Arg1176Ter)	Pathogenic
2028625	NM_001367624.2(ZNF469):c.5388del (p.Phe1796fs)	Pathogenic
2033690	NM_001367624.2(ZNF469):c.526G>T (p.Glu176Ter)	Pathogenic
2035422	NM_001367624.2(ZNF469):c.307del (p.Gln103fs)	Pathogenic
2059296	NM_001367624.2(ZNF469):c.4963_4964insT (p.Gly1655fs)	Pathogenic
2080449	NM_001367624.2(ZNF469):c.9268del (p.Arg3090fs)	Pathogenic
2084926	NM_001367624.2(ZNF469):c.4719_4722del (p.Gln1574fs)	Pathogenic
2113554	NM_001367624.2(ZNF469):c.7310del (p.Asp2437fs)	Pathogenic
2160380	NM_001367624.2(ZNF469):c.9063del (p.Ser3022fs)	Pathogenic
2423761	NC_000016.9:g.(?88493879)(88505740_?)del	Pathogenic
2626129	NM_001367624.2(ZNF469):c.4882_4883del (p.Thr1628fs)	Pathogenic
2695885	NM_001367624.2(ZNF469):c.3082dup (p.Arg1028fs)	Pathogenic
2699639	NM_001367624.2(ZNF469):c.6106del (p.Leu2035_Leu2036insTer)	Pathogenic
2704174	NM_001367624.2(ZNF469):c.17_29del (p.Pro6fs)	Pathogenic

SpliceAI

202 predictions. Top by Δscore:

Variant	Effect	Δscore
16:88429335:A:T	donor_gain	0.9400
16:88436049:CCCAG:C	acceptor_gain	0.9400
16:88436050:CCAGC:C	acceptor_gain	0.9400
16:88436051:CAG:C	acceptor_gain	0.9400
16:88427618:G:T	donor_gain	0.9300
16:88427617:G:GT	donor_gain	0.9100
16:88427669:C:T	donor_gain	0.9100
16:88427920:G:GA	donor_gain	0.9000
16:88436048:TCCCA:T	acceptor_gain	0.9000
16:88427599:G:GT	donor_gain	0.8800
16:88427919:T:TA	donor_gain	0.8800
16:88436052:AGC:A	acceptor_gain	0.8800
16:88427592:C:G	donor_gain	0.8500
16:88436053:G:T	acceptor_gain	0.8200
16:88429334:G:GT	donor_gain	0.7900
16:88428278:G:T	donor_gain	0.7500
16:88428026:G:GT	donor_gain	0.7200
16:88427678:G:T	donor_gain	0.7100
16:88428278:G:GT	donor_gain	0.6700
16:88429631:A:AG	acceptor_gain	0.6700
16:88429632:G:GG	acceptor_gain	0.6700
16:88427612:GCC:G	donor_gain	0.6600
16:88429605:ACCCC:A	acceptor_gain	0.6600
16:88427974:GAC:G	donor_gain	0.6500
16:88427609:G:GT	donor_gain	0.6200
16:88427668:G:GT	donor_gain	0.6200
16:88427683:G:T	donor_gain	0.6200
16:88429327:C:G	donor_gain	0.6100
16:88427734:G:T	donor_gain	0.6000
16:88427611:TGCC:T	donor_gain	0.5900

AlphaMissense

25459 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:88437506:T:C	F3318L	0.999
16:88437508:C:A	F3318L	0.999
16:88437508:C:G	F3318L	0.999
16:88437749:T:C	F3399L	0.999
16:88437751:C:A	F3399L	0.999
16:88437751:C:G	F3399L	0.999
16:88430060:T:C	F864L	0.998
16:88430062:C:A	F864L	0.998
16:88430062:C:G	F864L	0.998
16:88429706:T:C	F746L	0.997
16:88429707:T:C	F746S	0.997
16:88429708:C:A	F746L	0.997
16:88429708:C:G	F746L	0.997
16:88430057:A:C	S863R	0.997
16:88430059:C:A	S863R	0.997
16:88430059:C:G	S863R	0.997
16:88430061:T:C	F864S	0.997
16:88430061:T:G	F864C	0.997
16:88436927:T:C	F3125L	0.997
16:88436929:T:A	F3125L	0.997
16:88436929:T:G	F3125L	0.997
16:88437507:T:C	F3318S	0.997
16:88437507:T:G	F3318C	0.997
16:88437523:G:C	K3323N	0.997
16:88437523:G:T	K3323N	0.997
16:88437533:C:G	H3327D	0.997
16:88437535:C:A	H3327Q	0.997
16:88437535:C:G	H3327Q	0.997
16:88437750:T:C	F3399S	0.997
16:88429667:T:C	C733R	0.996

dbSNP variants (sampled 300 via entrez): RS1000010448 (16:88322561 C>G,T), RS1000024487 (16:88232860 C>T), RS1000030216 (16:88262917 C>A,G,T), RS1000036904 (16:88263014 G>A), RS1000038387 (16:88118831 C>T), RS1000038750 (16:88290841 C>G,T), RS1000038894 (16:88301344 C>T), RS1000047509 (16:88321056 G>A), RS1000049905 (16:88372522 C>A), RS1000079494 (16:88122429 A>G,T), RS1000083855 (16:88148429 C>G), RS1000106473 (16:88348479 C>T), RS1000113229 (16:88291114 C>T), RS1000114887 (16:88148341 C>T), RS1000118551 (16:88397788 A>G)

Disease associations

OMIM: gene MIM:612078 | disease phenotypes: MIM:229200, MIM:130000, MIM:148300, MIM:160700, MIM:192200, MIM:227650

GenCC curated gene-disease

Disease	Classification	Inheritance
brittle cornea syndrome 1	Definitive	Autosomal recessive
brittle cornea syndrome	Supportive	Autosomal recessive
aortic disorder	Limited	Autosomal dominant

Mondo (10): brittle cornea syndrome 1 (MONDO:0024543), Ehlers-Danlos syndrome (MONDO:0020066), keratoconus 1 (MONDO:0007851), keratoconus (MONDO:0015486), connective tissue disorder (MONDO:0003900), myopia (MONDO:0001384), brittle cornea syndrome (MONDO:0009242), varicose disease (MONDO:0008638), Fanconi anemia complementation group A (MONDO:0009215), aortic disorder (MONDO:0005561)

Orphanet (5): Brittle cornea syndrome (Orphanet:90354), Ehlers-Danlos syndrome (Orphanet:98249), Fanconi anemia (Orphanet:84), OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000481	Abnormal cornea morphology
HP:0000501	Glaucoma
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000559	Corneal scarring
HP:0000563	Keratoconus
HP:0000572	Visual loss
HP:0000592	Blue sclerae
HP:0000703	Dentinogenesis imperfecta
HP:0000939	Osteoporosis
HP:0000974	Hyperextensible skin
HP:0000977	Soft skin
HP:0000978	Bruising susceptibility
HP:0000987	Atypical scarring of skin
HP:0000993	Molluscoid pseudotumors
HP:0001119	Keratoglobus
HP:0001131	Corneal dystrophy
HP:0001166	Arachnodactyly
HP:0001288	Gait disturbance
HP:0001319	Neonatal hypotonia
HP:0001374	Congenital hip dislocation
HP:0001382	Joint hypermobility

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST000683_1	Central corneal thickness	9.000000e-11
GCST000775_5	Central corneal thickness	6.000000e-22
GCST001614_1	Central corneal thickness	1.000000e-12
GCST001806_25	Corneal structure	2.000000e-49
GCST002115_19	Axial length	7.000000e-08
GCST003479_9	Hair color	1.000000e-07
GCST003856_2	Central corneal thickness	2.000000e-08
GCST003856_5	Central corneal thickness	4.000000e-08
GCST005024_57	Pursuit maintenance gain	8.000000e-06
GCST005170_43	Intraocular pressure	4.000000e-12
GCST005580_203	Intraocular pressure	7.000000e-26
GCST005580_209	Intraocular pressure	4.000000e-24
GCST005667_16	Central corneal thickness	8.000000e-60
GCST005976_23	White blood cell count (basophil)	6.000000e-14
GCST006366_11	Central corneal thickness	8.000000e-38
GCST006979_640	Heel bone mineral density	1.000000e-13
GCST008276_6	Corneal resistance factor	5.000000e-11
GCST008277_4	Corneal hysteresis	2.000000e-08
GCST008315_9	Corneal hysteresis	7.000000e-06
GCST008317_2	Central corneal thickness	5.000000e-13
GCST008318_9	Corneal resistance factor	3.000000e-07
GCST008362_62	Birth weight	3.000000e-08
GCST009414_32	Central corneal thickness	9.000000e-58
GCST011390_8	Corneal resistance factor	2.000000e-109
GCST011391_6	Corneal hysteresis	2.000000e-92
GCST90000025_109	Appendicular lean mass	4.000000e-11
GCST90000654_65	Central corneal thickness	1.000000e-80
GCST90002385_53	High light scatter reticulocyte count	2.000000e-14
GCST90002386_291	High light scatter reticulocyte percentage of red cells	6.000000e-12
GCST90002405_315	Reticulocyte count	3.000000e-13

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004731	eye measurement
EFO:0004345	corneal topography
EFO:0005318	axial length measurement
EFO:0005213	central corneal thickness
EFO:0008433	pursuit maintenance gain measurement
EFO:0004695	intraocular pressure measurement
EFO:0005090	basophil count
EFO:0009270	heel bone mineral density
EFO:0010067	corneal resistance factor
EFO:0010066	corneal hysteresis
EFO:0004344	birth weight
EFO:0004980	appendicular lean mass
EFO:0007986	reticulocyte count

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D001018	Aortic Diseases	C14.907.109
D003240	Connective Tissue Diseases	C17.300
D004535	Ehlers-Danlos Syndrome	C14.907.454.240; C15.378.463.515.240; C16.131.831.428; C16.320.850.260; C17.300.200.310; C17.800.804.428; C17.800.827.260
D007640	Keratoconus	C11.204.627
D009216	Myopia	C11.744.636
D014648	Varicose Veins	C14.907.927
C536192	Brittle cornea syndrome 1 (supp.)
C563649	Keratoconus 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, decreases expression	3
Estradiol	affects expression, affects cotreatment, increases expression	3
Particulate Matter	increases abundance, increases expression, decreases expression	3
sodium arsenite	increases expression	2
Smoke	decreases expression, increases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Antimycin A	increases expression	1
Arsenicals	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	decreases expression	1
Cisplatin	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02596048	PHASE4	COMPLETED	A Multicenter Study of Iomeron®-400 Used With Multi-detector Computed Tomography Angiography (MDCTA)
NCT05246397	PHASE4	COMPLETED	Sugammadex Titration in Cardiac Surgery Patients
NCT04890431	PHASE4	UNKNOWN	Impact of Oxygen Therapy on Fatigue in Patients With Hypermobile-type Ehlers-Danlos Syndrome
NCT05603741	PHASE4	ACTIVE_NOT_RECRUITING	Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers
NCT01485211	PHASE4	COMPLETED	Corneal Thickness Changes During Corneal Collagen Cross-linking With Ultraviolet-A Irradiation and Riboflavin
NCT02119039	PHASE4	COMPLETED	Effect of CACICOL20 on Corneal Epithelial Healing After Cross-linking in Patients With Keratoconus
NCT03245853	PHASE4	COMPLETED	Epi-On Corneal Crosslinking for Keratoconus
NCT03429569	PHASE4	UNKNOWN	Cross-Linking ACcéléré Iontophorèse Confocal kératocONE
NCT04427956	PHASE4	COMPLETED	Corneal Crosslinking Treatment Study
NCT07474870	PHASE4	NOT_YET_RECRUITING	Outcomes of CTAK Surgery
NCT05279937	PHASE3	NOT_YET_RECRUITING	The Ultrasound-Guided Dextrose Prolotherapy in Ehlers-Danlos Syndrome Patients
NCT00371202	PHASE3	UNKNOWN	Comparison of Penetrating Keratoplasty and Deep Lamellar Keratoplasty With the Big Bubble Technique for Keratoconus
NCT00647699	PHASE3	COMPLETED	Corneal Collagen Cross-linking for Progressive Keratoconus
NCT00815256	PHASE3	UNKNOWN	Safety and Effectiveness of Collagen Cross Linking in Progressive Mild and Moderate Keratoconus
NCT00887900	PHASE3	COMPLETED	Deep Anterior Lamellar Keratoplasty (DALK)
NCT01112072	PHASE3	UNKNOWN	Corneal Collagen Crosslinking and Intacs for Keratoconus and Ectasia
NCT01152541	PHASE3	UNKNOWN	Corneal Collagen Crosslinking for Progressive Keratoconus and Ectasia Using Riboflavin/Dextran and Hypotonic Riboflavin
NCT01190306	PHASE3	TERMINATED	Safety Study of the VEGA UV-A System to Treat Keratoconus
NCT01344187	PHASE3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01459679	PHASE3	TERMINATED	Safety & Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery
NCT01464268	PHASE3	UNKNOWN	Transepithelial Corneal Collagen Crosslinking for Keratoconus and Corneal Ectasia
NCT01604135	PHASE3	ACTIVE_NOT_RECRUITING	Collagen Crosslinking for Keratoconus - a Randomized Controlled Clinical Trial
NCT01643226	PHASE3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01672814	PHASE3	COMPLETED	Microwave Treatment and Corneal Collagen Crosslinking for Keratoconus
NCT01682993	PHASE3	TERMINATED	Corneal Cross Linking and Topography Guided Excimer Laser Treatment
NCT01972854	PHASE3	TERMINATED	Safety and Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT02613780	PHASE3	UNKNOWN	Refractive Treatment of Early Keratoconus
NCT02638376	PHASE3	UNKNOWN	Evaluating the Safety and Efficacy of the KXL System for Corneal Collagen Cross-Linking in Eyes Having Keratoconus
NCT03080077	PHASE3	UNKNOWN	Safety and Effectiveness of Corneal Crosslinking (CXL): Keratoconus and Post-Refractive Ectasia
NCT03187912	PHASE3	COMPLETED	Accelerated Corneal Cross-linking With Different Riboflavin Solutions
NCT03442751	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Epi-on Corneal Cross-linking in Eyes With Progressive Keratoconus
NCT03858036	PHASE3	UNKNOWN	Corneal Collagen Cross-Linking (CXL) Performed With Epi-ON Versus Epi-OFF in Eyes With Keratoconus and Other Corneal Ectatic Disorders
NCT04897503	PHASE3	UNKNOWN	Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Riboflavin/Dextran or Riboflavin/Methylcellulose
NCT04905108	PHASE3	UNKNOWN	Transepithelial (Epi-on) Corneal Collagen Crosslinking to Treat Keratoconus and Corneal Ectasia
NCT05027295	PHASE3	UNKNOWN	Accelerated Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Pulse or Continuous UV-A Light
NCT06100939	PHASE3	ACTIVE_NOT_RECRUITING	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age With Keratoconus
NCT06100952	PHASE3	ACTIVE_NOT_RECRUITING	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age with Keratoconus
NCT06450470	PHASE3	RECRUITING	Use of a Freeze-dried Amniotic Membrane Post Crosslinking in Subjects With Progressive Keratoconus
NCT06601101	PHASE3	RECRUITING	Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus
NCT07124910	PHASE3	RECRUITING	Comparison of Epi-ON Corneal Collagen Crosslinking Performed Using an 18-Minute UVA Exposure vs. a 24-Minute UVA Exposure on Eyes With Ectatic Corneal Diseases