ARSG

Summary

ARSG (arylsulfatase G, HGNC:24102) is a protein-coding gene on chromosome 17q24.2, encoding Arylsulfatase G (Q96EG1). Displays arylsulfatase activity at acidic pH towards artificial substrates, such as p-nitrocatechol sulfate and also, but with a lower activity towards p-nitrophenyl sulfate and 4-methylumbelliferyl sulfate.

The protein encoded by this gene belongs to the sulfatase enzyme family. Sulfatases hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules. This protein displays arylsulfatase activity at acidic pH, as is typical of lysosomal sulfatases, and has been shown to localize in the lysosomes. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 22901 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Usher syndrome, type 4 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 634 total — 33 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• MANE Select transcript: NM_001267727

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24102
Approved symbol	ARSG
Name	arylsulfatase G
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1001
Ensembl gene	ENSG00000141337
Ensembl biotype	protein_coding
OMIM	610008
Entrez	22901

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding_CDS_not_defined, 3 protein_coding, 1 retained_intron

ENST00000448504, ENST00000452479, ENST00000578554, ENST00000578726, ENST00000581032, ENST00000582154, ENST00000590690, ENST00000621439

RefSeq mRNA: 13 — MANE Select: NM_001267727 NM_001267727, NM_001352899, NM_001352900, NM_001352901, NM_001352902, NM_001352903, NM_001352904, NM_001352905, NM_001352906, NM_001352907, NM_001352909, NM_001352910, NM_014960

CCDS: CCDS11676

Canonical transcript exons

ENST00000621439 — 12 exons

Exon	Start	End
ENSE00001598531	68306943	68307711
ENSE00003489898	68401360	68401450
ENSE00003537062	68356667	68356804
ENSE00003560204	68368548	68368744
ENSE00003575766	68347125	68347172
ENSE00003606570	68395073	68395193
ENSE00003614083	68351575	68351686
ENSE00003616583	68385064	68385172
ENSE00003655575	68370444	68370524
ENSE00003665430	68343604	68343791
ENSE00003717262	68420189	68420814
ENSE00003739640	68291495	68291568

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 88.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1408 / max 643.6026, expressed in 1380 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162404	3.5953	985
162405	1.6757	563
162406	1.0857	245
162403	1.0341	450
162396	0.6536	411
162402	0.2831	151
162407	0.2066	50
162413	0.1438	25
162425	0.1352	58
162414	0.1252	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	88.54	gold quality
stromal cell of endometrium	CL:0002255	87.87	gold quality
monocyte	CL:0000576	85.36	gold quality
leukocyte	CL:0000738	85.25	gold quality
granulocyte	CL:0000094	83.95	gold quality
bone marrow cell	CL:0002092	82.17	gold quality
thymus	UBERON:0002370	81.59	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.78	gold quality
bone marrow	UBERON:0002371	80.59	gold quality
adrenal tissue	UBERON:0018303	79.15	gold quality
cerebellar cortex	UBERON:0002129	78.66	gold quality
cerebellum	UBERON:0002037	78.62	gold quality
cerebellar hemisphere	UBERON:0002245	78.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.58	gold quality
endometrium	UBERON:0001295	78.18	gold quality
right adrenal gland	UBERON:0001233	77.78	gold quality
pituitary gland	UBERON:0000007	77.57	gold quality
adrenal gland	UBERON:0002369	77.42	gold quality
right adrenal gland cortex	UBERON:0035827	77.36	gold quality
left adrenal gland	UBERON:0001234	77.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.83	gold quality
sural nerve	UBERON:0015488	76.80	gold quality
left adrenal gland cortex	UBERON:0035825	76.68	gold quality
tonsil	UBERON:0002372	76.42	gold quality
apex of heart	UBERON:0002098	76.37	gold quality
cerebellar vermis	UBERON:0004720	76.37	gold quality
adenohypophysis	UBERON:0002196	76.36	gold quality
skeletal muscle tissue	UBERON:0001134	76.18	gold quality
gastrocnemius	UBERON:0001388	76.10	gold quality
lymph node	UBERON:0000029	75.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting ARSG, 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-3646	100.00	73.56	5283
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-657	99.48	66.02	848
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-4288	97.11	67.23	1636

Literature-anchored findings (GeneRIF, showing 11)

• molecular cloning and biochemical characterization of Arylsulfatase G [ARSG] (PMID:12461688)
• Arylsulfatase G is a novel lysosomal sulfatase and its expression is tissue-specific with highest expression in liver, kidney, and pancreas (PMID:18283100)
• Consistent genetic factors for ATP2B1, CSK, ARSG and CSMD1 were present, which have been shown to be associated with high blood pressure and hypertension in two Korean cohorts. (PMID:19960030)
• Genome-wide significance with musician’s dystonia was observed for an intronic variant in the arylsulfatase G (ARSG) gene (rs11655081; P = 3.95 x 10(-9) ; odds ratio [OR], 4.33; 95% confidence interval [CI], 2.66-7.05). (PMID:24375517)
• ARSG is differentially expressed, processed, and transported in tissues involving a membrane-associated pre-lysosomal precursor. (PMID:25135642)
• This study provide further support for a role of ARSG variants in task-specific dystonia, especially writer’s cramp. (PMID:25825126)
• We identified a homozygous founder missense variant, c.133G>T (p.D45Y) in arylsulfatase G (ARSG). All patients shared a distinctive retinal phenotype with ring-shaped atrophy along the arcades engirdling the fovea, resulting in ring scotoma. (PMID:29300381)
• No association of rs11655081 ARSG with blepharospasm was found in a Greek cohort. (PMID:30656493)
• New clinical and molecular evidence linking mutations in ARSG to Usher syndrome type IV. (PMID:33300174)
• Multimodal imaging and genetic findings in a case of ARSG-related atypical Usher syndrome. (PMID:33629623)
• Expanding the clinical phenotype in patients with disease causing variants associated with atypical Usher syndrome. (PMID:34223797)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	arsg	ENSDARG00000101715
		ENSDARG00000103261
mus_musculus	Arsg	ENSMUSG00000020604
rattus_norvegicus	Arsg	ENSRNOG00000003931
drosophila_melanogaster	CG18278	FBGN0033836
drosophila_melanogaster	CG7408	FBGN0036765
drosophila_melanogaster	CG7402	FBGN0036768
drosophila_melanogaster	CG32191	FBGN0052191
drosophila_melanogaster	CG30059	FBGN0260475

Paralogs (16): ARSD (ENSG00000006756), IDS (ENSG00000010404), ARSF (ENSG00000062096), ARSA (ENSG00000100299), STS (ENSG00000101846), ARSB (ENSG00000113273), GNS (ENSG00000135677), SULF1 (ENSG00000137573), GALNS (ENSG00000141012), ARSL (ENSG00000157399), ARSK (ENSG00000164291), ARSJ (ENSG00000180801), SGSH (ENSG00000181523), ARSI (ENSG00000183876), SULF2 (ENSG00000196562), ARSH (ENSG00000205667)

Protein

Protein identifiers

Arylsulfatase G — Q96EG1 (reviewed: Q96EG1)

Alternative names: N-sulfoglucosamine-3-sulfatase

All UniProt accessions (2): Q96EG1, J9JIG6

UniProt curated annotations — full annotation on UniProt →

Function. Displays arylsulfatase activity at acidic pH towards artificial substrates, such as p-nitrocatechol sulfate and also, but with a lower activity towards p-nitrophenyl sulfate and 4-methylumbelliferyl sulfate. Catalyzes the hydrolysis of the 3-sulfate groups of the N-sulfo-D-glucosamine 3-O-sulfate units of heparin.

Subcellular location. Lysosome.

Tissue specificity. Widely expressed, with very low expression in brain, lung, heart and skeletal muscle.

Post-translational modifications. N-glycosylated. N-glycosylated with both high mannose and complex type sugars. The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. The 63-kDa precursor undergoes proteolytic processing in two steps, yielding two fragments in the first step (apparent molecular masses of 44 and 18 kDa). In the second step, the 44-kDa fragment is processed further to the 34- and 10-kDa chains. The 10-kDa chain is a cleavage product of the 44-kDa fragment but linked to the 18-kDa chain through a disulfide bridge.

Disease relevance. Usher syndrome 4 (USH4) [MIM:618144] A form of Usher syndrome, a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish different types of Usher syndrome. USH4 is characterized by late onset of retinitis pigmentosa and usually late-onset of progressive sensorineural hearing loss without vestibular involvement. USH4 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by phosphate. The phosphate forms a covalent bond with the active site 3-oxoalanine.

Cofactor. Binds 1 Ca(2+) ion per subunit.

Similarity. Belongs to the sulfatase family.

RefSeq proteins (13): NP_001254656, NP_001339828, NP_001339829, NP_001339830, NP_001339831, NP_001339832, NP_001339833, NP_001339834, NP_001339835, NP_001339836, NP_001339838, NP_001339839, NP_055775 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000917	Sulfatase_N	Domain
IPR017850	Alkaline_phosphatase_core_sf	Homologous_superfamily
IPR024607	Sulfatase_CS	Conserved_site
IPR050738	Sulfatase	Family

Pfam: PF00884, PF14707

Catalyzed reactions (Rhea), 1 shown:

• an aryl sulfate + H2O = a phenol + sulfate + H(+) (RHEA:17261)

UniProt features (31 total): sequence variant 10, binding site 8, glycosylation site 4, active site 2, mutagenesis site 2, sequence conflict 2, signal peptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EG1-F1	91.90	0.86

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 (2): 84 (nucleophile); 139

Ligand- & substrate-binding residues (8): 302; 303; 44; 45; 84 (via 3-oxoalanine); 137; 162; 251

Post-translational modifications (1): 84

Glycosylation sites (4): 117, 215, 356, 497

Mutagenesis-validated functional residues (2):

Position	Phenotype
84	no sulfatase activity.
501	decrease of sulfatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1663150	The activation of arylsulfatases
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 133 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_VACUOLE_ORGANIZATION, KEGG_LYSOSOME, GOBP_NEUROGENESIS, TAL1ALPHAE47_01, AAAYRNCTG_UNKNOWN, MODULE_99, GOBP_NEURON_APOPTOTIC_PROCESS, RYTTCCTG_ETS2_B, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, REACTOME_SPHINGOLIPID_METABOLISM, GOBP_LYTIC_VACUOLE_ORGANIZATION, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_GLIAL_CELL_DIFFERENTIATION, FOXJ2_02

GO Biological Process (7): sulfur compound metabolic process (GO:0006790), lysosome organization (GO:0007040), glial cell differentiation (GO:0010001), gene expression (GO:0010467), homeostasis of number of cells (GO:0048872), neuron apoptotic process (GO:0051402), retina development in camera-type eye (GO:0060041)

GO Molecular Function (4): arylsulfatase activity (GO:0004065), N-sulfoglucosamine-3-sulfatase activity (GO:0033889), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), lysosome (GO:0005764), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1
Glycosphingolipid metabolism	1
Post-translational protein modification	1
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sulfuric ester hydrolase activity	2
metabolic process	1
lytic vacuole organization	1
cell differentiation	1
gliogenesis	1
macromolecule biosynthetic process	1
multicellular organismal-level homeostasis	1
apoptotic process	1
camera-type eye development	1
anatomical structure development	1
cation binding	1
catalytic activity	1
lytic vacuole	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARSG	CLN6	Q9NWW5	593
ARSG	CLN5	O75503	547
ARSG	ATP13A2	Q9NQ11	532
ARSG	CEP78	Q5JTW2	530
ARSG	CLN8	Q9UBY8	520
ARSG	IDUA	P35475	508
ARSG	C9orf153	Q5TBE3	508
ARSG	NAGLU	P54802	506
ARSG	PPT1	P50897	503
ARSG	HGSNAT	Q68CP4	499
ARSG	LGI2	Q8N0V4	480
ARSG	OR4X2	Q8NGF9	480
ARSG	OR4B1	Q8NGF8	477
ARSG	RIMBP2	O15034	474
ARSG	JPT2	Q9H910	463

IntAct

17 interactions, top by confidence:

A	B	Type	Score
DIPK1A	TMEM259	psi-mi:“MI:0914”(association)	0.530
ARSG	YDJC	psi-mi:“MI:0914”(association)	0.350
PTPRK	MANBA	psi-mi:“MI:0914”(association)	0.350
LYZL2	MANBA	psi-mi:“MI:0914”(association)	0.350
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
LYZL2	ZZEF1	psi-mi:“MI:0914”(association)	0.350
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
PDGFRA	QSOX1	psi-mi:“MI:0914”(association)	0.350
TRGV3	MANBA	psi-mi:“MI:0914”(association)	0.350
LIPG	TOR1B	psi-mi:“MI:0914”(association)	0.350
TM2D3	SPINT1	psi-mi:“MI:0914”(association)	0.350
B3GAT2	FAM20B	psi-mi:“MI:0914”(association)	0.350
ADAMTS12	LRP6	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): ARSG (Affinity Capture-MS), ARSG (Biochemical Activity), SUMF1 (Affinity Capture-MS), YDJC (Affinity Capture-MS), GSK3A (Affinity Capture-MS), TMEM214 (Affinity Capture-MS), ARSG (Affinity Capture-MS), MESDC2 (Affinity Capture-MS), CTAGE5 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), DPH1 (Affinity Capture-MS), IDE (Affinity Capture-MS), CGRRF1 (Affinity Capture-MS), QRSL1 (Affinity Capture-MS), ARSG (Affinity Capture-MS)

ESM2 similar proteins: A1A4K5, O14638, P06802, P08842, P15396, P15586, P15589, P15848, P22304, P22413, P33727, P50426, P50429, P51689, P51690, P54793, P97535, P97675, Q08890, Q08C93, Q13219, Q13822, Q1LZH9, Q32KH8, Q32KH9, Q32KJ9, Q3TYD4, Q5E9H0, Q5FYA8, Q5M900, Q5NDE3, Q5R5M5, Q5ZK90, Q60HH5, Q64610, Q66PG4, Q6DYE8, Q6NRQ1, Q6P9A2, Q6UWY0

Diamond homologs: P08842, P14000, P15289, P15589, P20713, P22304, P31447, P34059, P50427, P50428, P50473, P51689, P51690, P54793, Q08890, Q08DD1, Q32KH5, Q32KH8, Q32KH9, Q32KI9, Q32KJ6, Q32KJ8, Q32KJ9, Q3TYD4, Q571E4, Q5FYA8, Q5FYB1, Q60HH5, Q8WNQ7, Q96EG1, Q9X759, T2KMG4, P33727, P50430, Q32KH7, Q8A2F6, Q8A2H2, T2KMG7, P15848, P50429

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	33
Likely pathogenic	13
Uncertain significance	327
Likely benign	177
Benign	40

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1051129	NM_001267727.2(ARSG):c.454+1G>T	Pathogenic
1065124	NM_001267727.2(ARSG):c.1270C>T (p.Arg424Cys)	Pathogenic
1430743	NM_001267727.2(ARSG):c.914dup (p.Trp306fs)	Pathogenic
1443992	NM_001267727.2(ARSG):c.1267del (p.Val423fs)	Pathogenic
1461966	NM_001267727.2(ARSG):c.922C>T (p.Gln308Ter)	Pathogenic
1960975	NM_001267727.2(ARSG):c.983-2A>G	Pathogenic
1996932	NM_001267727.2(ARSG):c.1145_1146del (p.Gln382fs)	Pathogenic
2010220	NM_001267727.2(ARSG):c.1276G>T (p.Glu426Ter)	Pathogenic
2096527	NM_001267727.2(ARSG):c.1303+1G>A	Pathogenic
2112819	NM_001267727.2(ARSG):c.454+1G>A	Pathogenic
2576530	NM_001267727.2(ARSG):c.1212+1G>A	Pathogenic
2576531	NM_001267727.2(ARSG):c.275T>C (p.Leu92Pro)	Pathogenic
2576532	NM_001267727.2(ARSG):c.588C>A (p.Tyr196Ter)	Pathogenic
2576533	NM_001267727.2(ARSG):c.705-3940_982+2952del	Pathogenic
2723864	NM_001267727.2(ARSG):c.390C>A (p.Tyr130Ter)	Pathogenic
2833004	NM_001267727.2(ARSG):c.829dup (p.Asp277fs)	Pathogenic
2860488	NM_001267727.2(ARSG):c.1154_1155del (p.Arg385fs)	Pathogenic
3243184	NC_000017.10:g.(?66347696)(66347847_?)del	Pathogenic
3243185	NC_000017.10:g.(?66397481)(66397611_?)dup	Pathogenic
3621813	NM_001267727.2(ARSG):c.1046G>A (p.Trp349Ter)	Pathogenic
3662714	NM_001267727.2(ARSG):c.687del (p.Gln229fs)	Pathogenic
3726153	NM_001267727.2(ARSG):c.969del (p.Trp323fs)	Pathogenic
4710828	NM_001267727.2(ARSG):c.1005dup (p.Thr336fs)	Pathogenic
4729766	NM_001267727.2(ARSG):c.1261C>T (p.Gln421Ter)	Pathogenic
4805754	NM_001267727.2(ARSG):c.970C>T (p.Gln324Ter)	Pathogenic
585252	NM_001267727.2(ARSG):c.133G>T (p.Asp45Tyr)	Pathogenic
849065	NM_001267727.2(ARSG):c.701dup (p.Ser235fs)	Pathogenic
852327	NM_001267727.2(ARSG):c.100C>T (p.Gln34Ter)	Pathogenic
934156	NM_001267727.2(ARSG):c.283C>T (p.Arg95Trp)	Pathogenic
934158	NM_001267727.2(ARSG):c.566+3_566+8del	Pathogenic

SpliceAI

4939 predictions. Top by Δscore:

Variant	Effect	Δscore
17:68259422:GAGCA:G	donor_gain	1.0000
17:68259424:GCA:G	donor_gain	1.0000
17:68259427:G:GG	donor_gain	1.0000
17:68269342:CAAAC:C	acceptor_gain	1.0000
17:68269348:T:A	acceptor_loss	1.0000
17:68270834:ATTAC:A	donor_loss	1.0000
17:68270836:TA:T	donor_loss	1.0000
17:68270837:A:C	donor_loss	1.0000
17:68271660:A:AC	acceptor_gain	1.0000
17:68271665:C:CT	acceptor_gain	1.0000
17:68271666:A:T	acceptor_gain	1.0000
17:68271670:G:GC	acceptor_gain	1.0000
17:68272767:CCTG:C	acceptor_loss	1.0000
17:68272769:T:G	acceptor_loss	1.0000
17:68273923:TTA:T	donor_loss	1.0000
17:68273924:TACCA:T	donor_loss	1.0000
17:68273925:A:AC	donor_gain	1.0000
17:68273925:A:AT	donor_loss	1.0000
17:68273925:AC:A	donor_gain	1.0000
17:68273926:C:CA	donor_gain	1.0000
17:68273926:CC:C	donor_gain	1.0000
17:68273926:CCA:C	donor_gain	1.0000
17:68273926:CCAG:C	donor_gain	1.0000
17:68273926:CCAGA:C	donor_gain	1.0000
17:68274066:GGGAG:G	acceptor_gain	1.0000
17:68274067:GGAG:G	acceptor_gain	1.0000
17:68274068:GAG:G	acceptor_gain	1.0000
17:68274069:AG:A	acceptor_gain	1.0000
17:68274069:AGC:A	acceptor_loss	1.0000
17:68274070:GC:G	acceptor_loss	1.0000

AlphaMissense

3415 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:68347130:T:A	W138R	0.998
17:68347130:T:C	W138R	0.998
17:68347128:A:T	K137I	0.997
17:68307627:A:T	D45V	0.996
17:68307624:A:T	D44V	0.995
17:68370447:A:T	D302V	0.995
17:68385080:G:C	K333N	0.995
17:68385080:G:T	K333N	0.995
17:68343637:C:G	C84W	0.994
17:68347132:G:C	W138C	0.994
17:68347132:G:T	W138C	0.994
17:68343669:G:C	R95P	0.993
17:68343636:G:A	C84Y	0.992
17:68347129:A:C	K137N	0.992
17:68347129:A:T	K137N	0.992
17:68351577:T:C	F153L	0.992
17:68351579:T:A	F153L	0.992
17:68351579:T:G	F153L	0.992
17:68351604:A:C	S162R	0.992
17:68351606:C:A	S162R	0.992
17:68351606:C:G	S162R	0.992
17:68307627:A:C	D45A	0.991
17:68307628:C:A	D45E	0.991
17:68307628:C:G	D45E	0.991
17:68343635:T:C	C84R	0.991
17:68370447:A:C	D302A	0.991
17:68401434:G:C	K429N	0.991
17:68401434:G:T	K429N	0.991
17:68347125:G:T	G136V	0.990
17:68347128:A:C	K137T	0.990

dbSNP variants (sampled 300 via entrez): RS1000021650 (17:68318862 G>A), RS1000022114 (17:68417229 C>T), RS1000031048 (17:68358467 T>A), RS1000047717 (17:68442560 G>T), RS1000054925 (17:68417610 C>A), RS1000074772 (17:68449412 C>T), RS1000089183 (17:68403537 A>G), RS1000101031 (17:68357113 T>C), RS1000126721 (17:68374440 C>G,T), RS1000145471 (17:68448061 C>T), RS1000156978 (17:68402275 C>T), RS1000167453 (17:68425684 A>G), RS1000172158 (17:68295789 C>T), RS1000173191 (17:68350503 G>A), RS1000203376 (17:68339887 G>A)

Disease associations

OMIM: gene MIM:610008 | disease phenotypes: MIM:618144, MIM:101800, MIM:276900

GenCC curated gene-disease

Disease	Classification	Inheritance
Usher syndrome, type 4	Strong	Autosomal recessive
Usher syndrome type 3	Supportive	Autosomal recessive

Mondo (6): Usher syndrome, type 4 (MONDO:0029141), inherited retinal dystrophy (MONDO:0019118), Acrodysostosis 1 with or without hormone resistance (MONDO:0007044), Usher syndrome (MONDO:0019501), neural tube defect (MONDO:0018075), Usher syndrome type 3 (MONDO:0016485)

Orphanet (5): OBSOLETE: Inherited retinal disorder (Orphanet:71862), OBSOLETE: Acrodysostosis with multiple hormone resistance (Orphanet:280651), Usher syndrome (Orphanet:886), Neural tube defect (Orphanet:3388), Spina bifida and other spinal dysraphisms (Orphanet:823)

HPO phenotypes

20 total (21 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000375	Abnormal cochlea morphology
HP:0000407	Sensorineural hearing impairment
HP:0000408	Progressive sensorineural hearing impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000546	Retinal degeneration
HP:0000572	Visual loss
HP:0000575	Scotoma
HP:0000662	Nyctalopia
HP:0000716	Depression
HP:0000739	Anxiety
HP:0001105	Retinal atrophy
HP:0001133	Constriction of peripheral visual field
HP:0001751	Abnormal vestibular function
HP:0001756	Vestibular hyporeflexia
HP:0007730	Iris hypopigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0030529	Ring scotoma
HP:0030631	Hyperautofluorescent macular lesion
HP:0000556	Retinal dystrophy

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002319_2	Musician’s dystonia	4.000000e-09
GCST006922_1	Regular attendance at a religious group	2.000000e-06
GCST006923_7	Loneliness	6.000000e-09
GCST006924_5	Loneliness (MTAG)	1.000000e-09
GCST009261_2	Pallidum volume	7.000000e-06
GCST010245_97	LDL cholesterol levels	2.000000e-08
GCST90002404_172	Red cell distribution width	3.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009592	social interaction measurement
EFO:0007865	loneliness measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009188	Red cell distribution width

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009436	Neural Tube Defects	C10.500.680; C16.131.666.680
D058499	Retinal Dystrophies	C11.768.585.658
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2189124 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, decreases expression	4
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
trichostatin A	decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	decreases methylation	1
yessotoxin	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
azoxystrobin	affects expression	1
deguelin	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
thifluzamide	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
PP242	increases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2209028	Binding	Time dependent inhibition of human aryl sulfatase G at 0.1 uM to 1000 uM by para-nitrocatechol sulfate-based colorimetric assay	Evaluation of sulfatase-directed quinone methide traps for proteomics. — Bioorg Med Chem

Clinical trials (associated diseases)

71 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
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage 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]
NCT02065011	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Determine the Long-Term Safety, Tolerability and Biological Activity of SAR421869 in Patients With Usher Syndrome Type 1B
NCT06592131	PHASE1	NOT_YET_RECRUITING	BF844 Safety and Pharmacokinetic Study in Healthy Volunteers
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)
NCT02230072	PHASE1	COMPLETED	Fetoscopic Meningomyelocele Repair Study
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