SIX6

Summary

SIX6 (SIX homeobox 6, HGNC:10892) is a protein-coding gene on chromosome 14q23.1, encoding Homeobox protein SIX6 (O95475). May be involved in eye development.

The protein encoded by this gene is a homeobox protein that is similar to the Drosophila ‘sine oculis’ gene product. This gene is found in a cluster of related genes on chromosome 14 and is thought to be involved in eye development. Defects in this gene are a cause of isolated microphthalmia with cataract type 2 (MCOPCT2).

Source: NCBI Gene 4990 — RefSeq curated summary.

At a glance

• Gene–disease (curated): colobomatous optic disc-macular atrophy-chorioretinopathy syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 34
• Clinical variants (ClinVar): 15 total
• Phenotypes (HPO): 55
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_007374

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10892
Approved symbol	SIX6
Name	SIX homeobox 6
Location	14q23.1
Locus type	gene with protein product
Status	Approved
Aliases	Six9
Ensembl gene	ENSG00000184302
Ensembl biotype	protein_coding
OMIM	606326
Entrez	4990

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000327720

RefSeq mRNA: 1 — MANE Select: NM_007374 NM_007374

CCDS: CCDS9747

Canonical transcript exons

ENST00000327720 — 2 exons

Exon	Start	End
ENSE00001295668	60509146	60509970
ENSE00001845017	60511084	60512850

Expression profiles

Bgee: expression breadth broad, 34 present calls, max score 89.15.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6537 / max 139.3223, expressed in 101 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139884	0.3014	63
139882	0.1952	41
139881	0.0724	20
139883	0.0488	19
139885	0.0359	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	89.15	gold quality
pituitary gland	UBERON:0000007	89.10	gold quality
cranial nerve II	UBERON:0000941	81.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.18	gold quality
tibialis anterior	UBERON:0001385	62.72	silver quality
pancreatic ductal cell	CL:0002079	62.69	silver quality
deltoid	UBERON:0001476	55.19	silver quality
tendon of biceps brachii	UBERON:0008188	52.68	gold quality
ileal mucosa	UBERON:0000331	52.50	silver quality
hypothalamus	UBERON:0001898	52.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	52.22	gold quality
quadriceps femoris	UBERON:0001377	50.73	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
thymus	UBERON:0002370	49.90	gold quality
vastus lateralis	UBERON:0001379	49.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
muscle organ	UBERON:0001630	49.14	gold quality
gastrocnemius	UBERON:0001388	49.01	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	158.97
E-MTAB-6524	no	93.17
E-ANND-3	no	1.31

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CDKN1B

Upstream regulators (CollecTRI, top): LHX2, NKX3-1, PAX6

miRNA regulators (miRDB)

31 targeting SIX6, 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-5692A	100.00	74.40	6850
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-5591-3P	96.23	67.03	489
HSA-MIR-518A-3P	93.85	64.90	108
HSA-MIR-518B	93.85	64.62	111
HSA-MIR-518C-3P	93.85	64.62	111
HSA-MIR-518D-3P	93.85	64.59	111
HSA-MIR-518F-3P	93.85	64.93	108
HSA-MIR-526A-3P	93.85	65.32	108

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 31)

• No evidence was found that SIX6 mutations underlie human congenital structural eye malformations. (PMID:15505031)
• Six6 and Six2 differ in their DNA-binding mechanisms and in the consequences of their interaction with protein tyrosine phosphatase Eyes Absent in Six2/6-DNA-binding ability. (PMID:18293925)
• BOR and OAVS features are associated with duplication of SIX1, SIX6 and OTX2 resulting from a complex chromosomal rearrangement. (PMID:18666230)
• Our findings in humans and zebrafish suggest a functional involvement of six6b in early eye development, and open new insights into the genetic architecture of POAG. (PMID:24150847)
• we report a homozygous missense mutation of SIX6 associated with a unique eye phenotype characterized by optic disc anomalies, macular atrophy, and coloboma of the iris and chorioretina. (PMID:24702266)
• Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells. (PMID:24875647)
• Nonglaucomatous individuals with the SIX6 missense variant have reduced RNFL thickness in regions known to be particularly affected in those with glaucoma. (PMID:25537207)
• Single nucleotide polymorphism in SIX6 gene is associated with primary open angle glaucoma. (PMID:25798827)
• SIX6 and/or intraocular pressure promotes primary open-angle glaucoma by directly increasing p16INK4a expression. (PMID:26365380)
• Six1 regulates p53 via a dual mechanism involving upregulation of microRNA-27a and downregulation of RPL26. (PMID:26687066)
• study replicated the association of POAG with two SNPs at the SIX1-SIX6 locus and demonstrated that SNPs, rs10483727 and rs33912345, are significantly associated with POAG, especially with NTG in patients aged above 40 years (PMID:27260188)
• elevated expressions of SIX2, SIX4, and SIX6 predicted poor overall survival (OS) in NSCLC and poor relapse-free survival (RFS) in lung adenocarcinoma (PMID:27821176)
• we confirmed that rs33912345 and rs10483727-the only known cpRNFLT susceptibility SNPs-showed the strongest association with cpRNFLT of those within the SIX1/SIX6 locus. (PMID:28663559)
• The results suggest that SIX6 influences different stages of RGC differentiation and their survival; therefore, alteration in SIX6 function due to the risk allele may lead to cellular and molecular abnormalities. (PMID:28792678)
• We replicated the association of SNP rs10483727 in the SIX1/SIX6 locus with POAG in a Saudi cohort, suggesting its role in increasing susceptibility to Primary Open Angle Glaucoma . (PMID:29190129)
• Among 8 SNPs in 3 loci that showed at least nominal association (P < 5.00E-02) in the primary cohort, a representative SNP for each loci (rs2157719 for CDKN2B-AS1, rs33912345 for SIX6, and rs9913911 for GAS7) were selected (PMID:29261660)
• Mutation in SIX6 gene is associated with primary open angle glaucoma. (PMID:29405792)
• The BMP4- 152AA genotype might play role in the causation of congenital cataract, whereas BMP4-SIX6 V-N haplotype might play a protective role toward the development of congenital cataract and microphthalmia. (PMID:29692399)
• The protein-coding SIX6 variant rs33912345, previously associated with primary open-angle glaucoma (POAG), has a functional effect on glaucoma-associated optic nerve head traits in Europeans. (PMID:30005032)
• In conclusion, this study confirmed the association between two genome wide association study single nucleotide polymorphisms in SIX6 (rs33912345 and rs10483727) and primary open-angle glaucoma (POAG). (PMID:30586556)
• Results uncover the mechanism through which ceRNET_CC is regulated, identify novel roles for the six2/ceRNET_CC axis in regulating the stemness of breast cancer cells, and propose the possibility of targeting the six2/ceRNET_CC axis to inhibit breast cancer stem cell (CSC) traits. (PMID:30832689)
• This meta-analysis confirmed the association of rs10483727 and rs33912345 in SIX1-SIX6 with primary open-angle glaucoma (POAG). (PMID:31284308)
• Genetic prediction models for primary open-angle glaucoma: translational research. (PMID:31889028)
• Age-dependent regional retinal nerve fibre changes in SIX1/SIX6 polymorphism. (PMID:32719476)
• SIX6 is a TAL1-regulated transcription factor in T-ALL and associated with inferior outcome. (PMID:32835548)
• SIX6-related anophthalmia/microphthalmia: second report on a deletion in a consanguineous family. (PMID:33108933)
• Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children. (PMID:35017159)
• Association of Polymorphisms at the SIX1/SIX6 Locus With Normal Tension Glaucoma in a Korean Population. (PMID:35658088)
• Novel SIX6 mutations cause recessively inherited congenital cataract, microcornea, and corneal opacification with or without coloboma and microphthalmia. (PMID:35693420)
• Mutually exclusive epigenetic modification on SIX6 with hypermethylation for precancerous stage and metastasis emergence tracing. (PMID:35790732)
• Lack of association between SIX1/SIX6 locus polymorphisms and pseudoexfoliation syndrome in a population from the Republic of Korea. (PMID:36596020)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	six6a	ENSDARG00000025187
danio_rerio	six6b	ENSDARG00000031316
mus_musculus	Six6	ENSMUSG00000021099
rattus_norvegicus	Six6	ENSRNOG00000006296
drosophila_melanogaster	Optix	FBGN0025360
caenorhabditis_elegans		WBGENE00000453

Paralogs (6): SIX4 (ENSG00000100625), SIX1 (ENSG00000126778), SIX3 (ENSG00000138083), SIX2 (ENSG00000170577), SIX5 (ENSG00000177045), ANHX (ENSG00000227059)

Protein

Protein identifiers

Homeobox protein SIX6 — O95475 (reviewed: O95475)

Alternative names: Homeodomain protein OPTX2, Optic homeobox 2, Sine oculis homeobox homolog 6

All UniProt accessions (1): O95475

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in eye development.

Subunit / interactions. Interacts with TLE4 and TLE5.

Subcellular location. Nucleus.

Tissue specificity. Expressed in the developing and adult retina. Also expressed in the hypothalamic and the pituitary regions.

Disease relevance. Optic disk anomalies with retinal and/or macular dystrophy (ODRMD) [MIM:212550] An ocular disorder characterized by optic nerve dysplasia, optic disk anomalies, chorioretinal dystrophy and macular atrophy. Some patients have microphthalmia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SIX/Sine oculis homeobox family.

RefSeq proteins (1): NP_031400* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR031701	SIX1_SD	Domain

Pfam: PF00046, PF16878

UniProt features (12 total): modified residue 5, sequence variant 2, compositionally biased region 2, chain 1, DNA-binding region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95475-F1	81.68	0.62

Functional residue map

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

Post-translational modifications (5): 212, 221, 225, 227, 228

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 259 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, BENPORATH_ES_WITH_H3K27ME3, GCANCTGNY_MYOD_Q6, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, MODULE_45, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, MORF_RAD51L3, MODULE_66, MODULE_118, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, MODULE_379, MORF_CTSB, WCTCNATGGY_UNKNOWN, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS

GO Biological Process (4): eye development (GO:0001654), regulation of transcription by RNA polymerase II (GO:0006357), visual perception (GO:0007601), animal organ morphogenesis (GO:0009887)

GO Molecular Function (4): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
sensory organ development	1
visual system development	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
sensory perception of light stimulus	1
anatomical structure morphogenesis	1
animal organ development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIX6	OTX2	P32243	881
SIX6	DACH1	Q9UI36	877
SIX6	TMCO1	Q9UM00	720
SIX6	VSX2	P58304	701
SIX6	RHOJ	Q9H4E5	670
SIX6	ATOH7	Q8N100	670
SIX6	LBX1	P52954	669
SIX6	PAX6	P26367	657
SIX6	LHX2	P50458	629
SIX6	EYA2	O00167	611
SIX6	VAX2	Q9UIW0	592
SIX6	EYA1	Q99502	590
SIX6	GAS7	O60861	586
SIX6	BMP4	P12644	567
SIX6	GMDS	O60547	552
SIX6	LHX1	P48742	552

IntAct

13 interactions, top by confidence:

A	B	Type	Score
	SIX6	psi-mi:“MI:0915”(physical association)	0.370
CCL1	SIX6	psi-mi:“MI:0915”(physical association)	0.370
CCL26	SIX6	psi-mi:“MI:0915”(physical association)	0.370
CCL5	SIX6	psi-mi:“MI:0915”(physical association)	0.370
PPBP	SIX6	psi-mi:“MI:0915”(physical association)	0.370
XCL2	SIX6	psi-mi:“MI:0915”(physical association)	0.370
SIX6	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
SIX6	CLUH	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): TLE1 (Two-hybrid), AES (Two-hybrid), TLE1 (Reconstituted Complex), AES (Reconstituted Complex), TLE1 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), SIX3 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), CLUH (Affinity Capture-MS), AES (Affinity Capture-MS), GTF2A1L (Two-hybrid)

ESM2 similar proteins: A0A8M9QN10, A1YER0, A2ARM1, A2D5H2, E9Q0S6, O35260, O42406, O43147, O54943, O73916, O93307, O95343, O95475, P12813, P20263, P49335, P59729, Q13009, Q15475, Q1LVK9, Q5PQS0, Q5PRF9, Q5SXA9, Q5U464, Q62231, Q62232, Q62233, Q64249, Q6DHF9, Q6NXJ0, Q6NZ04, Q6TNU3, Q6ZUJ8, Q7TSI1, Q7TSZ8, Q80TC6, Q80XS6, Q8K3T2, Q8WYP3, Q91474

Diamond homologs: A1YER0, A2D5H2, A6NDR6, A8K0S8, A8WL06, B3DM47, B4F6V6, O00470, O04134, O04135, O14770, O17894, O22299, O35317, O35984, O42406, O46339, O65034, O73916, O80416, O93307, O95343, O95475, P10842, P24345, P40424, P40425, P40426, P40427, P41778, P41779, P41817, P46608, P46609, P46639, P46640, P48731, P53147, P56661, P56662

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TLE5	“down-regulates activity”	SIX6	binding
TLE1	“up-regulates activity”	SIX6	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

313 predictions. Top by Δscore:

Variant	Effect	Δscore
14:60511082:A:AG	acceptor_gain	0.9900
14:60511083:G:GG	acceptor_gain	0.9900
14:60511083:GA:G	acceptor_gain	0.9900
14:60509967:ACAG:A	donor_loss	0.9800
14:60509968:CAG:C	donor_loss	0.9800
14:60509969:AGG:A	donor_loss	0.9800
14:60509971:G:GC	donor_loss	0.9800
14:60509972:T:G	donor_loss	0.9800
14:60511080:GTA:G	acceptor_loss	0.9800
14:60511081:TAG:T	acceptor_loss	0.9800
14:60511082:A:AC	acceptor_loss	0.9800
14:60511083:G:GA	acceptor_loss	0.9800
14:60509969:AGGTC:A	donor_gain	0.9600
14:60511079:CGTAG:C	acceptor_gain	0.9600
14:60511083:GACT:G	acceptor_gain	0.9600
14:60510678:GC:G	donor_gain	0.9500
14:60510979:G:GT	donor_gain	0.9500
14:60511081:TAGA:T	acceptor_gain	0.9500
14:60511080:GTAGA:G	acceptor_gain	0.9400
14:60511083:GAC:G	acceptor_gain	0.9400
14:60511083:GACTC:G	acceptor_gain	0.9400
14:60509979:C:G	donor_gain	0.9100
14:60510948:G:GG	donor_gain	0.9100
14:60509873:C:G	donor_gain	0.9000
14:60511083:G:C	acceptor_gain	0.9000
14:60511082:AGAC:A	acceptor_gain	0.8900
14:60511078:CCGTA:C	acceptor_gain	0.8800
14:60509835:G:GA	donor_gain	0.8700
14:60511079:C:CA	acceptor_gain	0.8600
14:60509971:G:GG	donor_gain	0.8400

AlphaMissense

1576 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:60509450:T:C	C18R	1.000
14:60509451:G:A	C18Y	1.000
14:60509452:T:G	C18W	1.000
14:60509460:T:C	L21P	1.000
14:60509487:T:C	L30P	1.000
14:60509495:T:C	F33L	1.000
14:60509496:T:C	F33S	1.000
14:60509497:C:A	F33L	1.000
14:60509497:C:G	F33L	1.000
14:60509570:G:C	A58P	1.000
14:60509571:C:A	A58D	1.000
14:60509633:T:C	F79L	1.000
14:60509634:T:C	F79S	1.000
14:60509635:C:A	F79L	1.000
14:60509635:C:G	F79L	1.000
14:60509658:T:C	L87P	1.000
14:60509669:T:A	W91R	1.000
14:60509669:T:C	W91R	1.000
14:60509678:G:C	A94P	1.000
14:60509681:C:G	H95D	1.000
14:60509684:T:C	Y96H	1.000
14:60509684:T:G	Y96D	1.000
14:60509693:G:C	A99P	1.000
14:60509705:C:A	R103S	1.000
14:60509718:T:A	L107Q	1.000
14:60509720:G:A	G108R	1.000
14:60509720:G:C	G108R	1.000
14:60509721:G:A	G108E	1.000
14:60509727:T:A	V110E	1.000
14:60509729:G:C	D111H	1.000

dbSNP variants (sampled 300 via entrez): RS1000871189 (14:60513284 C>T), RS1001128109 (14:60508536 A>T), RS1001371834 (14:60509968 C>T), RS1001863872 (14:60510094 T>A,C), RS1002526000 (14:60508565 C>T), RS1003880364 (14:60512880 C>G), RS1004083551 (14:60508965 T>A), RS1005532041 (14:60512549 T>G), RS1005823401 (14:60510880 G>A), RS1005878036 (14:60507351 C>G), RS1006105217 (14:60511989 G>A), RS1006182696 (14:60510620 T>A,C), RS1006387148 (14:60507671 C>T), RS1007019573 (14:60510993 C>A,T), RS1007891844 (14:60510243 GA>G)

Disease associations

OMIM: gene MIM:606326 | disease phenotypes: MIM:206900, MIM:212550

GenCC curated gene-disease

Disease	Classification	Inheritance
colobomatous optic disc-macular atrophy-chorioretinopathy syndrome	Strong	Autosomal recessive
inherited retinal dystrophy	Limited	Autosomal recessive

Mondo (3): anophthalmia/microphthalmia-esophageal atresia syndrome (MONDO:0008799), colobomatous optic disc-macular atrophy-chorioretinopathy syndrome (MONDO:0008927), inherited retinal dystrophy (MONDO:0019118)

Orphanet (3): Microphthalmia-anophthalmia-coloboma (Orphanet:98555), Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome (Orphanet:435930), Anophthalmia/microphthalmia-esophageal atresia syndrome (Orphanet:77298)

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000541	Retinal detachment
HP:0000556	Retinal dystrophy
HP:0000557	Buphthalmos
HP:0000559	Corneal scarring
HP:0000567	Chorioretinal coloboma
HP:0000568	Microphthalmia
HP:0000589	Coloboma
HP:0000609	Optic nerve hypoplasia
HP:0000610	Abnormal choroid morphology
HP:0000612	Iris coloboma
HP:0000616	Miosis
HP:0000639	Nystagmus
HP:0000647	Sclerocornea
HP:0000666	Horizontal nystagmus
HP:0000902	Rib fusion
HP:0000921	Missing ribs
HP:0001252	Hypotonia
HP:0001263	Global developmental delay

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST000817_7	Height	6.000000e-17
GCST001451_3	Glaucoma (primary open-angle)	9.000000e-08
GCST001493_4	Glaucoma (primary open-angle)	4.000000e-11
GCST001858_24	Refractive error	1.000000e-08
GCST002541_97	Menarche (age at onset)	2.000000e-16
GCST002582_9	Glaucoma (primary open-angle)	2.000000e-17
GCST002626_12	Vertical cup-disc ratio	2.000000e-16
GCST002702_91	Height	2.000000e-07
GCST002762_1	Optic cup area	4.000000e-17
GCST002762_16	Optic cup area	2.000000e-27
GCST002763_1	Optic disc area	1.000000e-07
GCST003455_24	Spherical equivalent (joint analysis main effects and education interaction)	4.000000e-09
GCST003455_25	Spherical equivalent (joint analysis main effects and education interaction)	4.000000e-08
GCST003875_13	Gut microbiota (bacterial taxa)	3.000000e-09
GCST004075_3	Vertical cup-disc ratio	3.000000e-13
GCST004075_4	Vertical cup-disc ratio	3.000000e-18
GCST004076_31	Optic disc area	3.000000e-08
GCST004137_25	Optic cup area	1.000000e-19
GCST004137_41	Optic cup area	2.000000e-29
GCST005388_3	Glaucoma (primary open-angle)	2.000000e-11
GCST005919_2	Exhaled carbon monoxide levels in smokers with chronic obstructive pulmonary disease	6.000000e-08
GCST006065_44	Glaucoma (primary open-angle)	8.000000e-24
GCST006066_6	Glaucoma (primary open-angle)	6.000000e-13
GCST006067_7	Glaucoma (primary open-angle)	4.000000e-13
GCST006395_15	Glaucoma	6.000000e-22
GCST007944_6	Medication use (antiglaucoma preparations and miotics)	1.000000e-12
GCST008647_19	Urinary sodium excretion	1.000000e-09
GCST009404_14	Optic cup area	2.000000e-24
GCST009411_3	Optic disc area	3.000000e-12
GCST009412_4	Vertical cup-disc ratio	3.000000e-16

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004784	self reported educational attainment
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0006520	carbon monoxide exhalation measurement
EFO:0009944	Antiglaucoma preparations and miotics use measurement
EFO:0009282	sodium measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
C565876	Microphthalmia, Isolated, with Cataract 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases expression	2
apocarotenal	increases expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
mercuric bromide	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
bisphenol S	decreases methylation	1
Acetaminophen	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Aflatoxin B1	decreases methylation	1
beta Carotene	increases expression	1
p-Chloromercuribenzoic Acid	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A6F4	SEES3-1V human SIX6, clone1	Embryonic stem cell	Male
CVCL_A6F5	SEES3-1V human SIX6, clone2	Embryonic stem cell	Male
CVCL_A6F6	SEES3-1V human SIX6, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT07529041	Not specified	ENROLLING_BY_INVITATION	Real-time Acoustic Biofeedback for Enhancing Fixation Stability: A Proof-of-concept Study to Improve Ophthalmic Imaging Diagnostic Quality