CRYGS

Summary

CRYGS (crystallin gamma S, HGNC:2417) is a protein-coding gene on chromosome 3q27.3, encoding Gamma-crystallin S (P22914). Crystallins are the dominant structural components of the vertebrate eye lens.

Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins typically lacking connecting peptides and terminal extensions. They are differentially regulated after early development. This gene encodes a protein initially considered to be a beta-crystallin but the encoded protein is monomeric and has greater sequence similarity to other gamma-crystallins. This gene encodes the most significant gamma-crystallin in adult eye lens tissue. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation.

Source: NCBI Gene 1427 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 20 multiple types (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 70 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_017541

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2417
Approved symbol	CRYGS
Name	crystallin gamma S
Location	3q27.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000213139
Ensembl biotype	protein_coding
OMIM	123730
Entrez	1427

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000307944, ENST00000392499, ENST00000460288

RefSeq mRNA: 1 — MANE Select: NM_017541 NM_017541

CCDS: CCDS3275

Canonical transcript exons

ENST00000307944 — 3 exons

Exon	Start	End
ENSE00000969192	186539355	186539597
ENSE00001177892	186544306	186544380
ENSE00003479633	186538443	186538968

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 96.77.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7766 / max 813.0412, expressed in 52 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45972	0.7766	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lens of camera-type eye	UBERON:0000965	96.77	gold quality
cerebellar hemisphere	UBERON:0002245	85.71	gold quality
cerebellar cortex	UBERON:0002129	85.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.34	gold quality
cerebellum	UBERON:0002037	83.82	gold quality
granulocyte	CL:0000094	83.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.59	gold quality
right lobe of liver	UBERON:0001114	81.13	gold quality
mucosa of transverse colon	UBERON:0004991	80.85	gold quality
lower esophagus mucosa	UBERON:0035834	80.68	gold quality
apex of heart	UBERON:0002098	80.51	gold quality
spleen	UBERON:0002106	80.46	gold quality
body of pancreas	UBERON:0001150	79.08	gold quality
right adrenal gland cortex	UBERON:0035827	79.08	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.94	gold quality
right lobe of thyroid gland	UBERON:0001119	78.28	gold quality
metanephros cortex	UBERON:0010533	78.01	gold quality
transverse colon	UBERON:0001157	77.70	gold quality
left lobe of thyroid gland	UBERON:0001120	77.09	gold quality
right adrenal gland	UBERON:0001233	77.09	gold quality
left adrenal gland cortex	UBERON:0035825	77.08	gold quality
right uterine tube	UBERON:0001302	77.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.89	gold quality
lower esophagus	UBERON:0013473	76.88	gold quality
right frontal lobe	UBERON:0002810	76.84	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.77	gold quality
tibial nerve	UBERON:0001323	76.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.44	gold quality
body of stomach	UBERON:0001161	76.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting CRYGS, 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-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-4799-3P	97.78	65.97	893
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-4720-5P	97.46	65.67	893
HSA-MIR-5588-5P	97.46	65.70	913
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-4776-5P	97.14	66.63	405
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-3156-5P	96.93	67.36	800
HSA-MIR-6724-5P	96.41	63.11	507

Literature-anchored findings (GeneRIF, showing 39)

• Deamidation in cataractous lenses is influenced by surface exposure. (PMID:12093281)
• A lens gamma S-crystallin has been identified with an in vivo modification, S-methylation of cysteine residues, that may block intermolecular disulfide bondng and serve as a form of protection against cataract. (PMID:12475213)
• when glutathione becomes bound to gammaS-crystallin, it causes it to bind in turn to the beta-crystallin polypeptides to form a dimer (PMID:14763903)
• analysis of folding and stability of the isolated Greek key domains of the long-lived human lens proteins gammaD-crystallin and gammaS-crystallin (PMID:17905830)
• report a novel missense mutation, p.V42M, in CRYGS associated with bilateral congenital cataract in a family of Indian origin (PMID:19262743)
• Fast charge transfer quenching is an evolved property of the gamma S-crystallin fold, probably protecting it from ultraviolet-induced photodamage. (PMID:19358562)
• Results confirm the high stability of wild-type HgammaS-crystallin and demonstrates that the G18V mutation destabilizes the protein toward heat and GuHCl-induced unfolding. (PMID:19558189)
• Partially folded aggregation intermediates of human gammaD-, gammaC-, and gammaS-crystallin are recognized and bound by human alphaB-crystallin. (PMID:20621668)
• Molecular dynamics (MD) simulations, circular dichroism (CD), and dynamic light scattering (DLS) measurements were used to investigate the aggregation propensity of the eye-lens protein gammaS-crystallin. (PMID:21244846)
• The presence of significant amounts of small peptides derived from gammaS- and betaB1-crystallins in the water-insoluble fraction of the lens indicates that these interact tightly with cytoskeletal or membrane components. (PMID:21447408)
• Novel mutations in the crystalline genes have been identified in Chinese families with congenital cataracts. (PMID:21866213)
• The degree of deamidation for Gln92 and Gln170 was found to increase from birth to teen-age years and then to remain constant for four decades. (PMID:22593035)
• age-dependent cleavage of gammaS-crystallin generates a peptide that binds to cell membranes (PMID:22995907)
• replacement of valine in position 42 by the longer and bulkier methionine in human gammaS-crystallin perturbs the compact beta-sheet core packing topology in the N-terminal domain of the molecule (PMID:23284690)
• The cataract-associated mutant D26G of human gammaS-crystallin is remarkably close to the wild type molecule in structural features, with only a microenvironmental change in the packing around the mutation site. (PMID:23761725)
• The effects of the V41M mutation on the structural changes of gamma S-crystallin were studied. (PMID:24287181)
• novel mutation (G57W) in CRYGS in this Chinese family is associated with autosomal dominant pulverulent cataract. (PMID:24328668)
• The data suggest that enhanced attractive protein-protein interactions, arising from the deamidation of HGS, promote protein aggregation, thereby leading to increased light scattering and opacity over time. (PMID:26158710)
• Cataract-related G18V point mutation affects CRYGS stability and hydration. (PMID:27052457)
• aberrant modifications in gammaS-crystallin structure might contribute to the lower stability and higher aggregatory potency of the mutated protein, which subsequently resulted in cataracts in the patients (PMID:29857103)
• The Tyr67Asn substitution was predicted to decrease the local hydrophobicity and affect the three-dimensional structure of gammaS-crystallin, and resulted in a portion of mutant protein translocation from the cytoplasm to cell membrane. This observations expand the mutation spectrum of CRYGS and provide further evidence for the genetic basis and molecular mechanism of congenital cataract. (PMID:29964096)
• These results highlight the vital role of conserved Tyr corners in stabilizing Greek key motifs in gammaS crystallin and provide useful structural and functional insights into the mechanism of cataract formation in humans. (PMID:30391002)
• Molecular structure of G57W mutant of human CRYGS and its involvement in cataract formation has been reported. (PMID:30769148)
• This study reports conformational dynamics in CRYGS for the first time with crucial consequence of cataract formation. (PMID:30827504)
• These results establish a direct conformational link between the structure, dynamics, design and function in human gamma S-crystallin such that the G57W cataract variant promotes enhanced structural excursions concomitant with increased instability, elucidating very crucial molecular details of cataract formation affecting infants across the globe. (PMID:31084934)
• This work highlights functional aspects of structural malleability in human crystallin gamma S. Chemical shift curvatures indicate structural ruggedness in crystallin gamma S-G57W variant causing cataracts. (PMID:31092325)
• Kinetic Stability of Long-Lived Human Lens gamma-Crystallins and Their Isolated Double Greek Key Domains. (PMID:31266635)
• It has been proposed that domain interface acts as an intrinsic stabilizer for the otherwise floppy N-terminal domain in CRYGS G57W than in the wild-type protein where it serves an extrinsic role. (PMID:31371024)
• Zn2+-driven aggregation of gamma S crystallin proceeds through cysteine coordination, whereas Cu2+-driven aggregation results from methionine oxidation. (PMID:31647219)
• Human alphaB-crystallin distinguishes between highly similar variants of a structural crystallin, binding the cataract-related gammaS-G18V variant, but not the function-preserving gammaS-G18A variant, which is monomeric at physiological temperature. (PMID:31812542)
• The cataract-related S39C variant increases gammaS-crystallin sensitivity to environmental stress by destroying the intermolecular disulfide cross-links. (PMID:32234236)
• ATP antagonizes the crowding-induced destabilization of the human eye-lens protein gammaS-crystallin. (PMID:32307080)
• Cumulative deamidations of the major lens protein gammaS-crystallin increase its aggregation during unfolding and oxidation. (PMID:32697405)
• Cataract-causing G18V eliminates the antagonization by ATP against the crowding-induced destabilization of human gammaS-crystallin. (PMID:32753316)
• ATP differentially antagonizes the crowding-induced destabilization of human gammaS-crystallin and its four cataract-causing mutants. (PMID:33004175)
• A novel F30S mutation in gammaS-crystallin causes autosomal dominant congenital nuclear cataract by increasing susceptibility to stresses. (PMID:33454329)
• Human gammaS-Crystallin Resists Unfolding Despite Extensive Chemical Modification from Exposure to Ionizing Radiation. (PMID:35021623)
• The 18th amino acid glycine plays an essential role in maintaining the structural stabilities of gammaS-crystallin linking with congenital cataract. (PMID:37586630)
• Human gammaS-Crystallin Mutation F10_Y11delinsLN in the First Greek Key Pair Destabilizes and Impairs Tight Packing Causing Cortical Lamellar Cataract. (PMID:37762633)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	crygs2	ENSDARG00000041171
danio_rerio	crygs1	ENSDARG00000042992
mus_musculus	Crygs	ENSMUSG00000033501
rattus_norvegicus	Crygs	ENSRNOG00000038355

Paralogs (14): CRYBG3 (ENSG00000080200), CRYBB3 (ENSG00000100053), CRYBB1 (ENSG00000100122), CRYBA1 (ENSG00000108255), CRYBG1 (ENSG00000112297), CRYGD (ENSG00000118231), CRYGN (ENSG00000127377), CRYGC (ENSG00000163254), CRYBA2 (ENSG00000163499), CRYGA (ENSG00000168582), CRYBG2 (ENSG00000176092), CRYGB (ENSG00000182187), CRYBA4 (ENSG00000196431), CRYBB2 (ENSG00000244752)

Protein

Protein identifiers

Gamma-crystallin S — P22914 (reviewed: P22914)

Alternative names: Beta-crystallin S, Gamma-S-crystallin

All UniProt accessions (2): A0A140CTX8, P22914

UniProt curated annotations — full annotation on UniProt →

Function. Crystallins are the dominant structural components of the vertebrate eye lens.

Subunit / interactions. Monomer.

Disease relevance. Cataract 20, multiple types (CTRCT20) [MIM:116100] An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT20 includes progressive polymorphic anterior, posterior, or peripheral cortical. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Has a two-domain beta-structure, folded into four very similar Greek key motifs.

Similarity. Belongs to the beta/gamma-crystallin family.

RefSeq proteins (1): NP_060011* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001064	Beta/gamma_crystallin	Domain
IPR011024	G_crystallin-like	Homologous_superfamily
IPR050252	Beta/Gamma-Crystallin	Family

Pfam: PF00030

UniProt features (47 total): strand 16, sequence conflict 10, helix 6, sequence variant 4, domain 4, turn 2, region of interest 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
7N38	X-RAY DIFFRACTION	1.22
7N37	X-RAY DIFFRACTION	1.3
7N3A	X-RAY DIFFRACTION	1.5
7N39	X-RAY DIFFRACTION	1.56
7N36	X-RAY DIFFRACTION	2
7N3B	X-RAY DIFFRACTION	2.09
6FD8	X-RAY DIFFRACTION	2.1
1HA4	X-RAY DIFFRACTION	2.4
7NJE	X-RAY DIFFRACTION	3
2M3T	SOLUTION NMR
2M3U	SOLUTION NMR
6IF9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22914-F1	95.63	0.96

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GGGACCA_MIR133A_MIR133B, GOBP_EPITHELIUM_DEVELOPMENT, AAAYRNCTG_UNKNOWN, AP1_Q4_01, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, WTGAAAT_UNKNOWN, TGANTCA_AP1_C, SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP, NRF2_Q4, GOBP_SENSORY_PERCEPTION, COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_DN, GOBP_SENSORY_ORGAN_DEVELOPMENT

GO Biological Process (3): morphogenesis of an epithelium (GO:0002009), lens development in camera-type eye (GO:0002088), visual perception (GO:0007601)

GO Molecular Function (2): structural constituent of eye lens (GO:0005212), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tissue morphogenesis	1
epithelium development	1
camera-type eye development	1
anatomical structure development	1
sensory perception of light stimulus	1
structural molecule activity	1
binding	1

Protein interactions and networks

STRING

485 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYGS	CRYAA	P02489	945
CRYGS	BFSP2	Q13515	925
CRYGS	GJA8	P48165	923
CRYGS	GJA3	Q9Y6H8	921
CRYGS	CRYAB	P02511	809
CRYGS	PITX3	O75364	802
CRYGS	BFSP1	Q12934	800
CRYGS	MIP	P30301	723
CRYGS	HSF4	Q9ULV5	703
CRYGS	LIM2	P55344	673
CRYGS	FOXE3	Q13461	642
CRYGS	TMEM114	B3SHH9	640
CRYGS	HSPB2	Q16082	639
CRYGS	PAX6	P26367	639
CRYGS	HSPB1	P04792	629

IntAct

15 interactions, top by confidence:

A	B	Type	Score
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
CRYAB	CRYGS	psi-mi:“MI:0407”(direct interaction)	0.560
LAIR2	LAMA5	psi-mi:“MI:0914”(association)	0.530
EOLA1	CRYGS	psi-mi:“MI:0915”(physical association)	0.400
TERF2IP	CRYGS	psi-mi:“MI:0915”(physical association)	0.370
TINF2	CRYGS	psi-mi:“MI:0915”(physical association)	0.370
CRYGS	POT1	psi-mi:“MI:0915”(physical association)	0.370
LAIR2	PLOD3	psi-mi:“MI:0914”(association)	0.350
HINT2	CST4	psi-mi:“MI:0914”(association)	0.350
RAI2	CRYGS	psi-mi:“MI:0914”(association)	0.350
CSTPP1	CRYGS	psi-mi:“MI:0914”(association)	0.350
CD3E	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): CRYAB (Reconstituted Complex), CRYGS (Synthetic Lethality), CRYGS (Affinity Capture-MS), CRYGS (Affinity Capture-MS), CRYGS (Affinity Capture-MS), CRYGS (Affinity Capture-MS), CRYGS (Affinity Capture-MS), CRYGS (Affinity Capture-MS), CRYGS (Affinity Capture-MS), CRYGS (Proximity Label-MS), CRYGS (Two-hybrid), CRYGS (Two-hybrid), CRYGS (Two-hybrid)

ESM2 similar proteins: A2IBY7, A3RLD7, A3RLD8, A3RLE1, A4L9I8, O35486, P02527, P02528, P02529, P02530, P02531, P04342, P04344, P04345, P06504, P07315, P07316, P07320, P08209, P0C5E9, P10065, P10066, P10067, P10068, P10112, P11844, P22914, P23005, P26444, P48646, P48647, P48649, P49152, P53673, P55164, P55940, P55941, Q03740, Q06254, Q06255

Diamond homologs: A2IBH5, A2IBY7, A2ICR5, A3RLD7, A3RLD8, A3RLE1, A3RLE2, A4L9I8, A4L9I9, A4QNB6, D3ZEG1, F6Q2R9, O35486, P02522, P02523, P02524, P02525, P02526, P02527, P02528, P02529, P02530, P02531, P04342, P04344, P04345, P05813, P06504, P07315, P07316, P07317, P07318, P07320, P07530, P08209, P0C5E9, P10042, P10043, P10065, P10066

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CRYGS	up-regulates	Maintenance_of_lens_transparency
CRYAB	“up-regulates activity”	CRYGS	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	45
Likely benign	7
Benign	6

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
16936	NM_017541.4(CRYGS):c.53G>T (p.Gly18Val)	Pathogenic
252949	NM_017541.4(CRYGS):c.30_31delinsAA (p.Phe10_Tyr11delinsLeuAsn)	Pathogenic
2734603	NM_017541.4(CRYGS):c.53G>A (p.Gly18Asp)	Pathogenic
617601	NM_017541.4(CRYGS):c.124G>A (p.Val42Met)	Pathogenic
1098390	NM_017541.4(CRYGS):c.23T>A (p.Ile8Asn)	Likely pathogenic
3026525	NM_017541.4(CRYGS):c.199T>A (p.Tyr67Asn)	Likely pathogenic
617600	NM_017541.4(CRYGS):c.116C>G (p.Ser39Cys)	Likely pathogenic

SpliceAI

885 predictions. Top by Δscore:

Variant	Effect	Δscore
3:186538964:CTAGG:C	acceptor_gain	1.0000
3:186539350:CTCA:C	donor_loss	1.0000
3:186539351:TCACC:T	donor_loss	1.0000
3:186539352:CAC:C	donor_loss	1.0000
3:186539353:A:AC	donor_gain	1.0000
3:186539353:A:T	donor_loss	1.0000
3:186539354:C:CC	donor_gain	1.0000
3:186539354:CCAG:C	donor_gain	1.0000
3:186540829:CAAA:C	acceptor_gain	1.0000
3:186538965:TAGG:T	acceptor_gain	0.9900
3:186538967:GG:G	acceptor_gain	0.9900
3:186538967:GGC:G	acceptor_loss	0.9900
3:186538969:C:CC	acceptor_gain	0.9900
3:186538969:C:CG	acceptor_loss	0.9900
3:186538970:T:G	acceptor_loss	0.9900
3:186538980:C:CT	acceptor_gain	0.9900
3:186539349:ACTC:A	donor_loss	0.9900
3:186539353:AC:A	donor_gain	0.9900
3:186539354:CC:C	donor_gain	0.9900
3:186539354:CCA:C	donor_gain	0.9900
3:186539603:G:GC	acceptor_gain	0.9900
3:186540823:C:CT	acceptor_gain	0.9900
3:186540824:A:T	acceptor_gain	0.9900
3:186540832:A:AC	acceptor_gain	0.9900
3:186540832:A:C	acceptor_gain	0.9900
3:186538966:AGG:A	acceptor_gain	0.9800
3:186539354:CCAGA:C	donor_gain	0.9800
3:186539598:C:CC	acceptor_gain	0.9800
3:186539603:G:C	acceptor_gain	0.9800
3:186540823:C:T	acceptor_gain	0.9800

AlphaMissense

1184 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:186538824:A:G	W137R	0.995
3:186538824:A:T	W137R	0.995
3:186539402:A:G	W73R	0.995
3:186539402:A:T	W73R	0.995
3:186539504:A:G	S39P	0.995
3:186538746:A:G	W163R	0.993
3:186538746:A:T	W163R	0.993
3:186539434:A:G	L62S	0.992
3:186539450:C:A	G57W	0.991
3:186539473:A:T	V49D	0.991
3:186539480:A:G	W47R	0.991
3:186539480:A:T	W47R	0.991
3:186539503:G:A	S39F	0.991
3:186539508:G:C	C37W	0.991
3:186539510:A:G	C37R	0.991
3:186539567:C:G	G18R	0.991
3:186539509:C:T	C37Y	0.990
3:186538845:A:G	C130R	0.989
3:186539372:A:G	C83R	0.988
3:186539449:C:T	G57E	0.988
3:186538724:A:T	V170D	0.987
3:186538744:C:A	W163C	0.987
3:186538744:C:G	W163C	0.987
3:186538793:C:A	G147V	0.987
3:186539449:C:A	G57V	0.987
3:186539471:A:C	Y50D	0.987
3:186539590:A:G	F10S	0.987
3:186538719:A:G	S172P	0.986
3:186538794:C:G	G147R	0.986
3:186539374:G:A	S82F	0.986

dbSNP variants (sampled 300 via entrez): RS1000161382 (3:186540819 T>C), RS1000194585 (3:186545321 A>T), RS1000683533 (3:186540539 G>A), RS1001614252 (3:186546185 T>C), RS1002139667 (3:186540979 C>T), RS1002453704 (3:186541381 C>T), RS1002469386 (3:186540704 T>C), RS1002698728 (3:186544642 CTT>C,CT,CTTT), RS1003143463 (3:186538084 T>C), RS1003177033 (3:186544910 T>C), RS1003291521 (3:186544608 C>A,G,T), RS1003630310 (3:186545746 G>A,C,T), RS1003707408 (3:186546160 A>C), RS1004206676 (3:186545855 T>C), RS1004295998 (3:186541137 T>G)

Disease associations

OMIM: gene MIM:123730 | disease phenotypes: MIM:116100, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract 20 multiple types	Definitive	Autosomal dominant
early-onset lamellar cataract	Supportive	Autosomal dominant
early-onset sutural cataract	Supportive	Autosomal dominant

Mondo (4): cataract 20 multiple types (MONDO:0007284), retinitis pigmentosa (MONDO:0019200), early-onset lamellar cataract (MONDO:0018611), early-onset sutural cataract (MONDO:0020372)

Orphanet (2): Early onset non-syndromic cataract (Orphanet:91492), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0003621	Juvenile onset
HP:0007971	Lamellar cataract
HP:0010695	Sutural cataract
HP:0100018	Nuclear cataract
HP:0100019	Cortical cataract

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002133_3	Illicit drug use	5.000000e-08
GCST005407_2	Glaucoma (primary open-angle)	3.000000e-07
GCST005409_2	Open-angle glaucoma and vertical cup-disc ratio	3.000000e-08
GCST007672_5	3-month functional outcome in ischaemic stroke (modified Rankin score)	9.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005431	illegal drug consumption
EFO:0006939	cup-to-disc ratio measurement
EFO:0009603	stroke outcome severity measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	2
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Cisplatin	decreases expression	1
Copper	affects cotreatment, increases expression	1
Fluorouracil	affects reaction, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa
NCT01068561	PHASE1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa