ASRGL1

Summary

ASRGL1 (asparaginase and isoaspartyl peptidase 1, HGNC:16448) is a protein-coding gene on chromosome 11q12.3, encoding Isoaspartyl peptidase/L-asparaginase (Q7L266). Has both L-asparaginase and beta-aspartyl peptidase activity.

Enables asparaginase activity and beta-aspartyl-peptidase activity. Involved in asparagine catabolic process via L-aspartate. Located in cytoplasm.

Source: NCBI Gene 80150 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited retinal dystrophy (Limited, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 309 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001083926

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16448
Approved symbol	ASRGL1
Name	asparaginase and isoaspartyl peptidase 1
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22316, ALP1, ALP
Ensembl gene	ENSG00000162174
Ensembl biotype	protein_coding
OMIM	609212
Entrez	80150

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000301776, ENST00000415229, ENST00000525496, ENST00000525708, ENST00000526096, ENST00000528206, ENST00000529226, ENST00000533970, ENST00000534183, ENST00000534571, ENST00000628829, ENST00000870124, ENST00000870125, ENST00000870126, ENST00000870127, ENST00000870128, ENST00000935951, ENST00000935952, ENST00000935953, ENST00000935954, ENST00000956001, ENST00000956002

RefSeq mRNA: 2 — MANE Select: NM_001083926 NM_001083926, NM_025080

CCDS: CCDS8019

Canonical transcript exons

ENST00000415229 — 7 exons

Exon	Start	End
ENSE00001063097	62389133	62389251
ENSE00001063099	62391522	62391632
ENSE00001801006	62337890	62338167
ENSE00002149030	62392079	62393412
ENSE00002176270	62337448	62337574
ENSE00003658475	62356987	62357144
ENSE00003714901	62356325	62356467

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 97.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5413 / max 279.2216, expressed in 1203 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114684	9.5413	1203

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.82	gold quality
male germ cell	CL:0000015	97.57	gold quality
right uterine tube	UBERON:0001302	97.45	gold quality
putamen	UBERON:0001874	97.45	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.42	gold quality
left testis	UBERON:0004533	97.37	gold quality
adult organism	UBERON:0007023	97.24	gold quality
nasal cavity epithelium	UBERON:0005384	97.14	gold quality
ventral tegmental area	UBERON:0002691	97.11	gold quality
right testis	UBERON:0004534	97.05	gold quality
amygdala	UBERON:0001876	96.86	gold quality
cerebellar vermis	UBERON:0004720	96.85	gold quality
substantia nigra pars compacta	UBERON:0001965	96.68	gold quality
substantia nigra	UBERON:0002038	96.67	gold quality
caudate nucleus	UBERON:0001873	96.63	gold quality
midbrain	UBERON:0001891	96.60	gold quality
lateral globus pallidus	UBERON:0002476	96.49	gold quality
right frontal lobe	UBERON:0002810	96.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.89	gold quality
cingulate cortex	UBERON:0003027	95.69	gold quality
anterior cingulate cortex	UBERON:0009835	95.69	gold quality
cerebellar hemisphere	UBERON:0002245	95.62	gold quality
hypothalamus	UBERON:0001898	95.61	gold quality
cerebellar cortex	UBERON:0002129	95.55	gold quality
subthalamic nucleus	UBERON:0001906	95.38	gold quality
testis	UBERON:0000473	95.37	gold quality
cerebellum	UBERON:0002037	95.33	gold quality
nucleus accumbens	UBERON:0001882	95.31	gold quality
superior vestibular nucleus	UBERON:0007227	95.28	gold quality
metanephros cortex	UBERON:0010533	95.28	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	755.30
E-MTAB-10287	yes	642.53
E-MTAB-3929	no	577.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting ASRGL1, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3180-5P	99.82	69.12	2422
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-3120-3P	99.54	70.28	2669
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-922	99.02	67.23	1838

Literature-anchored findings (GeneRIF, showing 15)

• Human ALP cDNA was subsequently cloned. It showed 77% identity to the rat ALP sequence and the gene, ASRGL1 (asparaginase-like 1), mapped to chromosome locus 11q12.3. (PMID:11984834)
• Overexpression of CRASH is associated with metastatic breast cancer. (PMID:19414332)
• ASRGL1 exhibits beta-aspartyl peptidase activity consistent with plant-type asparaginases. ASRGL1 is shown to be an Ntn hydrolase for which Thr168 serves as the essential N-terminal nucleophile for intramolecular processing and catalysis. (PMID:19839645)
• Determined is the structure of the first mammalian plant-type asparaginase in both a precursor and fully activated form. (PMID:22891768)
• Reduced expression of ASRGL1, defined as <75% positively stained tumor cells, was significantly associated with poor prognosis and reduced disease-specific survival in endometrioid endometrial adenocarcinoma (EEA). (PMID:25858696)
• Multiple negatively charged small molecules interact within the active site of ASRGL1 to act as a base in promoting cleavage. (PMID:26780688)
• Our studies suggest that the p.G178R mutation in ASRGL1 leads to photoreceptor degeneration resulting in progressive vision loss. (PMID:27106100)
• In a prospective setting ASRGL1 validates as a strong prognostic biomarker in endometrial carcinoma. Loss of ASRGL1 is associated with aggressive disease and poor survival. (PMID:29096882)
• A panel including p53 and ASRGL1 immunohistochemistry was identified as the most accurate predictor of relapse-free and disease-specific survival. Within this panel, patients were allocated into high- (5.9%), intermediate- (29.5%) and low- (64.6%) risk groups where high-risk patients had a 30-fold risk (P<0.001) of dying of EEC compared to the low-risk group. (PMID:29486992)
• The strongest associations between protein abundance and Alzheimer’s disease severity were found for APLP1, CNTN2 and SPP1 proteins The best discrimination between mild cognitive impairment vs. controls was observed with a model combining APLP1 and SPP1 proteins. (PMID:29684683)
• ASRGL1 was closely associated with growth and apoptosis in cervical cancer. Therefore, ASRGL1 may be a novel, potentially effective anticervical cancer therapy. (PMID:29767260)
• The role of the quaternary structure in the activation of human L-asparaginase. (PMID:32434038)
• ASRGL1 downregulation suppresses hepatocellular carcinoma tumorigenesis in a CDK1-dependent manner. (PMID:36572570)
• l-Asparaginase regulates mTORC1 activity via a TSC2-dependent pathway in pancreatic beta cells. (PMID:36842323)
• TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression. (PMID:38755145)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	asrgl1	ENSDARG00000021681
mus_musculus	Asrgl1	ENSMUSG00000024654
rattus_norvegicus	Asrgl1	ENSRNOG00000020202
drosophila_melanogaster	CG7860	FBGN0030653

Paralogs (2): AGA (ENSG00000038002), TASP1 (ENSG00000089123)

Protein

Protein identifiers

Isoaspartyl peptidase/L-asparaginase — Q7L266 (reviewed: Q7L266)

Alternative names: Asparaginase-like protein 1, Beta-aspartyl-peptidase, Isoaspartyl dipeptidase, L-asparagine amidohydrolase

All UniProt accessions (6): A0A024R573, A0A087WUG3, A0A087WZI5, A0A087X1T8, Q7L266, E9PJK6

UniProt curated annotations — full annotation on UniProt →

Function. Has both L-asparaginase and beta-aspartyl peptidase activity. May be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions. Is highly active with L-Asp beta-methyl ester. Besides, has catalytic activity toward beta-aspartyl dipeptides and their methyl esters, including beta-L-Asp-L-Phe, beta-L-Asp-L-Phe methyl ester (aspartame), beta-L-Asp-L-Ala, beta-L-Asp-L-Leu and beta-L-Asp-L-Lys. Does not have aspartylglucosaminidase activity and is inactive toward GlcNAc-L-Asn. Likewise, has no activity toward glutamine.

Subunit / interactions. Heterodimer of an alpha and beta chain produced by autocleavage. This heterodimer may then dimerize in turn, giving rise to a heterotetramer.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in brain, kidney, testis and tissues of the gastrointestinal tract. Present in sperm (at protein level). Over-expressed in uterine, mammary, prostatic and ovarian carcinoma.

Post-translational modifications. Cleaved into an alpha and beta chain by autocatalysis; this activates the enzyme. The N-terminal residue of the beta subunit is responsible for the nucleophile hydrolase activity.

Activity regulation. Glycine accelerates autocleavage into an alpha and beta chain.

Induction. By 5-alpha-di-hydrotestosterone and progesterone.

Similarity. Belongs to the Ntn-hydrolase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7L266-1	1	yes
Q7L266-2	2

RefSeq proteins (2): NP_001077395, NP_079356 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000246	Peptidase_T2	Family
IPR029055	Ntn_hydrolases_N	Homologous_superfamily
IPR033844	ASRGL1_meta	Family

Pfam: PF01112

Enzyme classification (BRENDA):

• EC 3.4.19.5 — beta-aspartyl-peptidase (BRENDA: 8 organisms, 47 substrates, 3 inhibitors, 31 Km, 29 kcat entries)
• EC 3.5.1.1 — asparaginase (BRENDA: 169 organisms, 249 substrates, 394 inhibitors, 319 Km, 145 kcat entries)

Substrate kinetics (BRENDA)

27 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-ASPARAGINE	0.0009–1732.5	193
L-GLUTAMINE	0.034–130.35	23
L-ASPARTYL-BETA-HYDROXAMATE	0.011–1.9	19
L-GLN	0.005–70	17
BETA-ASP-LEU	0.09–34	15
BETA-ASP-HIS	2.38–12.6	13
L-ASN	0.0002–7.4	12
ASN	0.0048–4.7	7
N-ACETYL-L-ASPARAGINE	0.597–5.613	4
BETA-ASP-PHE	0.23–0.49	3
D-ASPARAGINE	1.2–24.1	3
GLN	0.0058–6.26	3
ALPHA-ASP-LEU	5–6.9	2
BETA-ASP-ALA	1.2–3.7	2
BETA-ASP-GLY	4.7–18	2

Catalyzed reactions (Rhea), 1 shown:

• L-asparagine + H2O = L-aspartate + NH4(+) (RHEA:21016)

UniProt features (39 total): strand 15, helix 9, turn 4, chain 2, binding site 2, mutagenesis site 2, sequence conflict 1, active site 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
4O0C	X-RAY DIFFRACTION	1.5
4O0E	X-RAY DIFFRACTION	1.71
4PVR	X-RAY DIFFRACTION	1.75
4PVS	X-RAY DIFFRACTION	1.84
4PVP	X-RAY DIFFRACTION	1.85
4OSY	X-RAY DIFFRACTION	1.91
4O0F	X-RAY DIFFRACTION	1.92
4O0D	X-RAY DIFFRACTION	1.95
4OSX	X-RAY DIFFRACTION	1.95
4O0H	X-RAY DIFFRACTION	1.97
4O0G	X-RAY DIFFRACTION	2.1
4PVQ	X-RAY DIFFRACTION	2.13
3TKJ	X-RAY DIFFRACTION	2.3
4ZM9	X-RAY DIFFRACTION	2.51
4ET0	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L266-F1	94.20	0.89

Functional residue map

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

Catalytic / active sites (1): 168 (nucleophile)

Ligand- & substrate-binding residues (2): 196–199; 219–222

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (2):

Position	Phenotype
168	abolishes activation by autocleavage. abolishes enzyme activity.
168	strongly reduced enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8964208	Phenylalanine metabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives
R-HSA-8963691	Phenylalanine and tyrosine metabolism

MSigDB gene sets: 165 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, TGCGCANK_UNKNOWN, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, LIAO_METASTASIS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_AMINO_ACID_CATABOLIC_PROCESS, LIU_CMYB_TARGETS_UP, LIU_VMYB_TARGETS_UP, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR

GO Biological Process (2): proteolysis (GO:0006508), obsolete L-asparagine catabolic process via L-aspartate (GO:0033345)

GO Molecular Function (4): asparaginase activity (GO:0004067), beta-aspartyl-peptidase activity (GO:0008798), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (4): photoreceptor inner segment (GO:0001917), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Phenylalanine and tyrosine metabolism	1
Metabolism	1
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein metabolic process	1
amidase activity	1
omega peptidase activity	1
threonine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASRGL1	ASPG	Q86U10	935
ASRGL1	TUBGCP2	Q9BSJ2	562
ASRGL1	KIAA2013	Q8IYS2	475
ASRGL1	PPP1R26	Q5T8A7	462
ASRGL1	MYCBPAP	Q8TBZ2	438
ASRGL1	PDXDC1	Q6P996	437
ASRGL1	SLC7A5	Q01650	418
ASRGL1	CYP39A1	Q9NYL5	415
ASRGL1	MYO1D	O94832	408
ASRGL1	OTUD4	Q01804	404
ASRGL1	RCC2	Q9P258	400
ASRGL1	MAD1L1	Q9Y6D9	391
ASRGL1	LIN7A	O14910	389
ASRGL1	STEEP1	Q9H5V9	385
ASRGL1	IDH3B	O43837	383

IntAct

17 interactions, top by confidence:

A	B	Type	Score
STMN2	MTA2	psi-mi:“MI:0914”(association)	0.530
ERBB2	ASRGL1	psi-mi:“MI:0915”(physical association)	0.370
GSK3B	ASRGL1	psi-mi:“MI:0915”(physical association)	0.370
ASRGL1	MAP2K5	psi-mi:“MI:0915”(physical association)	0.370
ASRGL1	TAB1	psi-mi:“MI:0915”(physical association)	0.370
MAPK8IP2	ASRGL1	psi-mi:“MI:0915”(physical association)	0.370
NMI	TARSL2	psi-mi:“MI:0914”(association)	0.350
MDM4	TP73	psi-mi:“MI:0914”(association)	0.350
NMI	TARS3	psi-mi:“MI:0914”(association)	0.350
USB1	IGLL5	psi-mi:“MI:0914”(association)	0.350
TRIM72	CCDC22	psi-mi:“MI:0914”(association)	0.350
PLD2	DNAJB5	psi-mi:“MI:0914”(association)	0.350
SLC66A1LP	UBB	psi-mi:“MI:0914”(association)	0.350
PIK3R6	HSPA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): ASRGL1 (Affinity Capture-MS), ASRGL1 (Affinity Capture-MS), ASRGL1 (Affinity Capture-MS), ASRGL1 (Affinity Capture-MS), ASRGL1 (Two-hybrid), ASRGL1 (Proximity Label-MS), ASRGL1 (Proximity Label-MS), ASRGL1 (Proximity Label-MS), ASRGL1 (Affinity Capture-MS), ASRGL1 (Affinity Capture-MS), ASRGL1 (Affinity Capture-MS), ASRGL1 (Affinity Capture-MS), ASRGL1 (Affinity Capture-MS), ASRGL1 (Affinity Capture-MS), ASRGL1 (Affinity Capture-MS)

ESM2 similar proteins: A1CM94, B3N6Y7, B4GGF2, B4HT15, B4JVW6, B4NWI1, B4QHB1, B8FLU0, O02467, O23710, P20933, P30362, P30364, P30919, P38946, P42240, P44459, P50252, P50288, P74383, Q1E406, Q21697, Q28Y14, Q29I93, Q47898, Q4R6C4, Q4R7U8, Q54BC8, Q54QR2, Q56W64, Q58626, Q5A6A4, Q5AYR1, Q64191, Q6BNC5, Q6FLI1, Q6GM78, Q6LYR8, Q7L266, Q8C0M9

Diamond homologs: A3MUS8, B3N6Y7, B4GGF2, B4HT15, B4NWI1, B4QHB1, O02467, O57971, P30362, P30364, P37595, P50287, P50288, P74383, Q28Y14, Q29I93, Q32LE5, Q47898, Q4R6C4, Q4R7U8, Q54WW4, Q5BKW9, Q5JHT1, Q6GM78, Q7CQV5, Q7L266, Q8C0M9, Q8GXG1, Q8MR45, Q8R1G1, Q8U4E6, Q8VI04, Q8YQB1, Q9H6P5, Q9V262, Q9VXT7, Q9ZSD6, B3MJ16, B3NN96, B4GHE3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	178
Likely benign	113
Benign	13

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
563873	GRCh37/hg19 11q12.1-12.3(chr11:58935215-62177656)x3	Likely pathogenic

SpliceAI

1653 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62338164:GCAG:G	donor_gain	1.0000
11:62338166:AGGTA:A	donor_loss	1.0000
11:62338168:G:A	donor_loss	1.0000
11:62356979:T:A	acceptor_loss	1.0000
11:62356979:T:TA	acceptor_gain	1.0000
11:62356980:G:A	acceptor_gain	1.0000
11:62356983:TCAGA:T	acceptor_loss	1.0000
11:62356984:CAG:C	acceptor_loss	1.0000
11:62356985:A:AG	acceptor_gain	1.0000
11:62356985:AGACA:A	acceptor_loss	1.0000
11:62356986:G:GA	acceptor_gain	1.0000
11:62356986:GA:G	acceptor_gain	1.0000
11:62356986:GAC:G	acceptor_gain	1.0000
11:62356986:GACA:G	acceptor_gain	1.0000
11:62356986:GACAC:G	acceptor_gain	1.0000
11:62357142:AAA:A	donor_gain	1.0000
11:62357142:AAAGT:A	donor_loss	1.0000
11:62357143:AA:A	donor_gain	1.0000
11:62357143:AAGT:A	donor_loss	1.0000
11:62357145:G:GG	donor_gain	1.0000
11:62357145:GTA:G	donor_loss	1.0000
11:62357146:T:A	donor_loss	1.0000
11:62371103:T:TA	acceptor_gain	1.0000
11:62389127:T:TA	acceptor_gain	1.0000
11:62389132:GA:G	acceptor_gain	1.0000
11:62389132:GAA:G	acceptor_gain	1.0000
11:62389132:GAAAC:G	acceptor_gain	1.0000
11:62337571:CTGGG:C	donor_loss	0.9900
11:62337573:GG:G	donor_gain	0.9900
11:62337574:GG:G	donor_gain	0.9900

AlphaMissense

1996 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62356369:G:C	A79P	0.991
11:62389152:G:C	A171P	0.989
11:62389195:C:T	S185F	0.989
11:62389237:A:T	D199V	0.987
11:62338158:T:C	F61L	0.985
11:62338160:C:A	F61L	0.985
11:62338160:C:G	F61L	0.985
11:62356372:A:C	S80R	0.985
11:62356374:T:A	S80R	0.985
11:62356374:T:G	S80R	0.985
11:62389156:T:A	V172D	0.985
11:62389195:C:A	S185Y	0.985
11:62392213:G:C	A286P	0.985
11:62338145:A:C	E56D	0.984
11:62338145:A:T	E56D	0.984
11:62389227:C:A	R196S	0.984
11:62389228:G:C	R196P	0.984
11:62391537:C:A	A209D	0.984
11:62391570:G:A	G220E	0.984
11:62389188:G:C	A183P	0.983
11:62389238:C:A	D199E	0.983
11:62389238:C:G	D199E	0.983
11:62356405:G:C	A91P	0.982
11:62389158:G:C	A173P	0.982
11:62389236:G:C	D199H	0.982
11:62392096:G:C	A247P	0.982
11:62389189:C:A	A183E	0.981
11:62391554:G:C	A215P	0.981
11:62356451:G:C	R106P	0.980
11:62389198:C:T	T186I	0.980

dbSNP variants (sampled 300 via entrez): RS1000017071 (11:62378487 G>C), RS1000031432 (11:62364663 T>G), RS1000090850 (11:62371914 A>G), RS1000122886 (11:62355800 G>A,C), RS1000156768 (11:62373345 C>T), RS1000160040 (11:62401338 T>G), RS1000171989 (11:62382446 A>G), RS1000237888 (11:62355925 C>G), RS1000324745 (11:62376443 T>G), RS1000396040 (11:62351684 T>G), RS1000412853 (11:62342446 C>T), RS1000423411 (11:62376618 T>G), RS1000428565 (11:62357450 C>G,T), RS1000468576 (11:62389938 T>C,G), RS1000476250 (11:62336819 A>G)

Disease associations

OMIM: gene MIM:609212 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
inherited retinal dystrophy	Limited	Autosomal recessive

Mondo (1): inherited retinal dystrophy (MONDO:0019118)

Orphanet (1): OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000556	Retinal dystrophy

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001737_1	Chronic obstructive pulmonary disease-related biomarkers	1.000000e-10
GCST005956_12	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_37	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07
GCST006979_796	Heel bone mineral density	1.000000e-09
GCST008154_38	Trunk fat mass	3.000000e-07
GCST008157_57	Body fat mass	4.000000e-06
GCST012020_183	Serum metabolite levels	2.000000e-12
GCST012021_108	Serum metabolite levels	2.000000e-12
GCST90020027_1462	Waist-hip index	5.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005080	CC16 measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009270	heel bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
bisphenol A	affects expression, affects cotreatment, decreases expression	2
sodium arsenite	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
Progesterone	affects cotreatment, increases expression, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
Genistein	increases cleavage, increases reaction, affects cotreatment, decreases expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	increases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
chromium hexavalent ion	increases abundance, decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1

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