SPATA7

Summary

SPATA7 (spermatogenesis associated 7, HGNC:20423) is a protein-coding gene on chromosome 14q31.3, encoding Spermatogenesis-associated protein 7 (Q9P0W8). Involved in the maintenance of both rod and cone photoreceptor cells.

This gene, originally isolated from testis, is also expressed in retina. Mutations in this gene are associated with Leber congenital amaurosis and juvenile retinitis pigmentosa. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 55812 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited retinal dystrophy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 498 total — 46 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 72
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_018418

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20423
Approved symbol	SPATA7
Name	spermatogenesis associated 7
Location	14q31.3
Locus type	gene with protein product
Status	Approved
Aliases	HSD3
Ensembl gene	ENSG00000042317
Ensembl biotype	protein_coding
OMIM	609868
Entrez	55812

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 9 protein_coding, 9 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000045347, ENST00000356583, ENST00000393545, ENST00000553303, ENST00000553626, ENST00000553885, ENST00000553908, ENST00000554102, ENST00000554168, ENST00000554802, ENST00000555356, ENST00000555401, ENST00000555515, ENST00000555534, ENST00000555715, ENST00000556406, ENST00000556553, ENST00000556666, ENST00000556870, ENST00000557248, ENST00000557567, ENST00000557724, ENST00000879181

RefSeq mRNA: 2 — MANE Select: NM_018418 NM_001040428, NM_018418

CCDS: CCDS32132, CCDS9883

Canonical transcript exons

ENST00000393545 — 12 exons

Exon	Start	End
ENSE00002432674	88385657	88385837
ENSE00002490100	88437838	88438460
ENSE00003466763	88396156	88396203
ENSE00003504530	88391381	88391455
ENSE00003572816	88429348	88429463
ENSE00003597881	88431172	88431225
ENSE00003613875	88433135	88433212
ENSE00003613934	88427630	88427696
ENSE00003669319	88393393	88393488
ENSE00003670187	88437543	88437597
ENSE00003677292	88416711	88416844
ENSE00003688847	88426232	88426704

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 94.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.1483 / max 165.0971, expressed in 1712 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140955	8.5029	1688
140956	2.6454	1125

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.37	gold quality
sperm	CL:0000019	94.35	gold quality
left testis	UBERON:0004533	94.22	gold quality
testis	UBERON:0000473	92.89	gold quality
male germ cell	CL:0000015	92.04	gold quality
calcaneal tendon	UBERON:0003701	92.03	gold quality
tendon	UBERON:0000043	89.45	gold quality
bronchial epithelial cell	CL:0002328	87.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.50	gold quality
right uterine tube	UBERON:0001302	87.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.82	gold quality
cerebellar cortex	UBERON:0002129	86.60	gold quality
cerebellar hemisphere	UBERON:0002245	86.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.43	gold quality
medial globus pallidus	UBERON:0002477	85.82	gold quality
left ovary	UBERON:0002119	85.73	gold quality
cerebellum	UBERON:0002037	85.54	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.54	gold quality
tendon of biceps brachii	UBERON:0008188	85.33	gold quality
right ovary	UBERON:0002118	85.20	gold quality
pituitary gland	UBERON:0000007	85.16	gold quality
left lobe of thyroid gland	UBERON:0001120	84.97	gold quality
right lobe of thyroid gland	UBERON:0001119	84.79	gold quality
adenohypophysis	UBERON:0002196	84.60	gold quality
thyroid gland	UBERON:0002046	84.57	gold quality
ovary	UBERON:0000992	84.39	gold quality
right frontal lobe	UBERON:0002810	84.35	gold quality
cortical plate	UBERON:0005343	84.34	gold quality
islet of Langerhans	UBERON:0000006	84.25	gold quality
adult organism	UBERON:0007023	84.16	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-110499	yes	133.48
E-ANND-3	yes	6.19
E-GEOD-100618	no	396.95

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 13)

• isolation and characterization of HSD-3.1 expressed in the testis (PMID:12736779)
• Spata7 is expressed in the mature mouse retina. (PMID:19268277)
• analysis of the SPATA7 mutations in Leber congenital amaurosis and the associated phenotype (PMID:20104588)
• Mutations in SPATA7 are a rare cause of childhood retinal dystrophy accounting for 1.7% of disease in this cohort. (PMID:21310915)
• In conclusion, our data established the first linkage association of a loss-of-function mutation in the SPATA7 gene with a typical retinitis pigmentosa (RP) phenotype and not with leber congenital amaurosis or early onset RP. (PMID:22136677)
• Digenic and triallelic mutations of CRB1 and SPATA7 were detected in a Chinese family with Leber congenital amaurosis. The results imply that CRB1 and SPATA7 may not interact with each other directly. (PMID:22219627)
• SPATA7 plays a role in RPGRIP1-mediated protein trafficking across the connecting cilium of photoreceptor cells. Apoptotic degeneration of these cells triggered by protein mislocalization is a mechanism of disease progression in LCA3/juvenile RP patients (PMID:25398945)
• A novel homozygous large deletion in SPATA7 associated with juvenile retinitis pigmentosa has been found in a consanguineous Israeli Muslim Arab family. (PMID:25814828)
• The disease resulting from SPATA7 mutations in this patient initially presented as a cone-rod dystrophy (CRD), but changed over time into a phenotype more reminiscent of late-stage retinitis pigmentosa (RP). (PMID:26854980)
• We present the clinical and genetic findings of two siblings harboring the c.1112T>C/p.I371T homozygous mutation in the SPATA7 gene. (PMID:28481129)
• Compound heterozygous c.1100A > G, p.(Y367C) and c.1102_1103delCT, p.(L368Efs*4) variants in SPATA7 manifest as an unusual RP phenotype in this case, showing extensive choroidal sclerosis and retinal pigment epithelium (RPE) atrophy with evidence of progression over two years on multimodal imaging. (PMID:29411205)
• Narrow arterioles, a relatively well-preserved macular region, and widespread retinal pigment epithelium atrophy resulting in diffuse mottling hypopigmentation in the midperipheral retina may be considered early and common fundus changes specific to SPATA7-associated retinopathy. (PMID:31908400)
• SPATA7-Associated Juvenile Retinitis Pigmentosa in Two Brothers from a Consanguineous Iraqi Family in Switzerland. (PMID:37164434)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	spata7	ENSDARG00000075898
mus_musculus	Spata7	ENSMUSG00000021007
rattus_norvegicus	Spata7	ENSRNOG00000003955

Protein

Protein identifiers

Spermatogenesis-associated protein 7 — Q9P0W8 (reviewed: Q9P0W8)

Alternative names: HSD-3.1, Spermatogenesis-associated protein HSD3

All UniProt accessions (13): Q9P0W8, G3V287, G3V2E1, G3V2V4, G3V3D2, G3V491, G3V4A9, G3V5H6, G3V5N2, G3V5V8, H0YJ48, H0YJ93, V9HVY9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the maintenance of both rod and cone photoreceptor cells. It is required for recruitment and proper localization of RPGRIP1 to the photoreceptor connecting cilium (CC), as well as photoreceptor-specific localization of proximal CC proteins at the distal CC. Maintenance of protein localization at the photoreceptor-specific distal CC is essential for normal microtubule stability and to prevent photoreceptor degeneration.

Subunit / interactions. Found in a complex with CFAP410, NEK1 and SPATA7. Interacts with NEK1. Interacts with RPGRIP1. Interacts with RPGR. Interacts with NPHP4. Interacts with NPHP1. Interacts with AHI1.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Cilium basal body. Cell projection. Cilium. Photoreceptor outer segment.

Disease relevance. Leber congenital amaurosis 3 (LCA3) [MIM:604232] A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. The disease is caused by variants affecting the gene represented in this entry. Retinitis pigmentosa 94, variable age at onset, autosomal recessive (RP94) [MIM:604232] A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9P0W8-1	1	yes
Q9P0W8-2	2
Q9P0W8-3	3

RefSeq proteins (2): NP_001035518, NP_060888* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029357	SPATA7	Family

Pfam: PF15244

UniProt features (17 total): sequence variant 7, sequence conflict 5, splice variant 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0W8-F1	58.28	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 231 (showing top): XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOCC_MICROTUBULE_ORGANIZING_CENTER, CREB_Q4, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, WTGAAAT_UNKNOWN, CYTAGCAAY_UNKNOWN, AFP1_Q6, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_SENSORY_PERCEPTION, GOCC_NEURON_PROJECTION, GOBP_RETINA_HOMEOSTASIS

GO Biological Process (5): microtubule cytoskeleton organization (GO:0000226), visual perception (GO:0007601), photoreceptor cell maintenance (GO:0045494), protein localization to photoreceptor outer segment (GO:1903546), protein localization to photoreceptor connecting cilium (GO:1903621)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (10): axoneme (GO:0005930), microtubule cytoskeleton (GO:0015630), photoreceptor connecting cilium (GO:0032391), ciliary basal body (GO:0036064), rod photoreceptor outer segment (GO:0120200), photoreceptor distal connecting cilium (GO:0120206), photoreceptor outer segment (GO:0001750), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein localization to non-motile cilium	2
cytoskeleton	2
photoreceptor cell cilium	2
cytoskeleton organization	1
microtubule-based process	1
sensory perception of light stimulus	1
retina homeostasis	1
multicellular organismal process	1
protein localization to ciliary transition zone	1
binding	1
microtubule	1
ciliary plasm	1
ciliary transition zone	1
microtubule organizing center	1
cilium	1
photoreceptor outer segment	1
photoreceptor connecting cilium	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPATA7	RPGRIP1	Q96KN7	935
SPATA7	AIPL1	Q9NZN9	930
SPATA7	RDH12	Q96NR8	917
SPATA7	LRAT	O95237	902
SPATA7	RD3	Q7Z3Z2	892
SPATA7	LCA5	Q86VQ0	869
SPATA7	TULP1	O00294	861
SPATA7	RPE65	Q16518	857
SPATA7	IMPDH1	P20839	857
SPATA7	CEP290	O15078	830
SPATA7	CRX	O43186	818
SPATA7	RPGR	Q92834	789
SPATA7	IQCB1	Q15051	741
SPATA7	GUCY2D	Q02846	721
SPATA7	CERKL	Q49MI3	696

IntAct

23 interactions, top by confidence:

A	B	Type	Score
SPATA7	NUDT22	psi-mi:“MI:0915”(physical association)	0.400
SPATA7	AHI1	psi-mi:“MI:0915”(physical association)	0.370
SPATA7	NPHP4	psi-mi:“MI:0915”(physical association)	0.370
NPHP1	SPATA7	psi-mi:“MI:0915”(physical association)	0.370
RPGRIP1	SPATA7	psi-mi:“MI:0915”(physical association)	0.370
RPGR	SPATA7	psi-mi:“MI:0915”(physical association)	0.370
SPATA7	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
BNIP3L	HTRA2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
SPATA7	EEPD1	psi-mi:“MI:0914”(association)	0.350
N		psi-mi:“MI:0914”(association)	0.350
CBX2	LMNB1	psi-mi:“MI:0914”(association)	0.350
OGT	SMCHD1	psi-mi:“MI:0914”(association)	0.350
CFAP410	SPATA7	psi-mi:“MI:0915”(physical association)	0.000
RAF1	SPATA7	psi-mi:“MI:0915”(physical association)	0.000
RPGRIP1L	SPATA7	psi-mi:“MI:0915”(physical association)	0.000
NEK1	SPATA7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (32): SPATA7 (Two-hybrid), SPATA7 (Two-hybrid), SPATA7 (Affinity Capture-MS), SPATA7 (Affinity Capture-MS), SPATA7 (Affinity Capture-MS), SPATA7 (Affinity Capture-MS), SPATA7 (Affinity Capture-MS), SPATA7 (Affinity Capture-MS), SPATA7 (Affinity Capture-MS), SPATA7 (Co-fractionation), SPATA7 (Co-fractionation), CYB5R1 (Co-fractionation), SPATA7 (Affinity Capture-MS), SPATA7 (Affinity Capture-MS), C1orf21 (Affinity Capture-MS)

ESM2 similar proteins: A0AUZ9, A0JMF7, A1L2Y1, A3KMW7, A8MT70, A8MW92, A9JRX0, B0CM36, B0S6S9, B7ZS37, D3Z987, F1QB81, O95447, P40649, Q0IHW6, Q0P5X5, Q14B48, Q15468, Q3U285, Q3V089, Q49A88, Q4R815, Q4V9H5, Q5CZC0, Q5DTI6, Q5REF4, Q5T1N1, Q5ZJK5, Q66H35, Q6NRH7, Q6NRK3, Q6ZRS4, Q6ZU52, Q80VP2, Q80WQ8, Q8BLG0, Q8CB14, Q8CCJ9, Q8IUR6, Q8IX21

Diamond homologs: Q80VP2, Q9P0W8, Q9R0A3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	46
Likely pathogenic	15
Uncertain significance	249
Likely benign	124
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071024	NC_000014.8:g.(?88852143)(88904786_?)del	Pathogenic
1072160	NM_018418.5(SPATA7):c.1210G>T (p.Glu404Ter)	Pathogenic
1076482	NM_018418.5(SPATA7):c.265_268del (p.Leu89fs)	Pathogenic
1076992	NC_000014.8:g.(?88852163)(88862567_?)del	Pathogenic
1396	NM_018418.5(SPATA7):c.960dup (p.Pro321fs)	Pathogenic
1398	NM_018418.5(SPATA7):c.1395del (p.Gln465fs)	Pathogenic
1411536	NM_018418.5(SPATA7):c.969_975del (p.Gly324fs)	Pathogenic
1451496	NM_018418.5(SPATA7):c.418dup (p.Met140fs)	Pathogenic
1458662	NM_018418.5(SPATA7):c.700dup (p.Ser234fs)	Pathogenic
1686226	NM_018418.5(SPATA7):c.19+2T>A	Pathogenic
1713268	NM_018418.5(SPATA7):c.1418del (p.Met473fs)	Pathogenic
1802260	NM_018418.5(SPATA7):c.901_912+1del	Pathogenic
1967922	NM_018418.5(SPATA7):c.578_581dup (p.Ser195fs)	Pathogenic
2014731	NM_018418.5(SPATA7):c.864del (p.Thr289fs)	Pathogenic
2090160	NM_018418.5(SPATA7):c.1090G>T (p.Glu364Ter)	Pathogenic
2093809	NM_018418.5(SPATA7):c.1079_1080del (p.Tyr359_Ser360insTer)	Pathogenic
2100961	NM_018418.5(SPATA7):c.477_478del (p.Leu161fs)	Pathogenic
236497	NM_018418.5(SPATA7):c.1058dup (p.Ser354fs)	Pathogenic
2426472	NC_000014.8:g.(?88852163)(88904766_?)del	Pathogenic
2942222	NM_018418.5(SPATA7):c.1222del (p.Met408fs)	Pathogenic
30805	SPATA7, 3-BP DEL, 1227CAC	Pathogenic
3249373	NM_018418.5(SPATA7):c.487A>T (p.Lys163Ter)	Pathogenic
3249967	NM_018418.5:c.(912+1_913-1)_(1028+1_1029-1)del	Pathogenic
3250327	NM_018418.5(SPATA7):c.590_593dup (p.Tyr199fs)	Pathogenic
3751794	NM_018418.5(SPATA7):c.419del (p.Met140fs)	Pathogenic
3759255	NM_018418.5(SPATA7):c.296_297del (p.Glu99fs)	Pathogenic
3760323	NM_018418.5(SPATA7):c.224del (p.Ser75fs)	Pathogenic
427862	NM_018418.5(SPATA7):c.1215G>T (p.Glu405Asp)	Pathogenic
4784537	NM_018418.5(SPATA7):c.943G>T (p.Glu315Ter)	Pathogenic
4785847	NM_018418.5(SPATA7):c.168_169del (p.Tyr56_Asn57delinsTer)	Pathogenic

SpliceAI

2579 predictions. Top by Δscore:

Variant	Effect	Δscore
14:88385811:GAC:G	donor_gain	1.0000
14:88391379:A:AG	acceptor_gain	1.0000
14:88391380:G:GG	acceptor_gain	1.0000
14:88396154:A:AG	acceptor_gain	1.0000
14:88396155:G:GA	acceptor_gain	1.0000
14:88396155:GCT:G	acceptor_gain	1.0000
14:88396202:GT:G	donor_gain	1.0000
14:88396204:G:GG	donor_gain	1.0000
14:88416709:A:AG	acceptor_gain	1.0000
14:88416710:G:GG	acceptor_gain	1.0000
14:88416844:GGT:G	donor_loss	1.0000
14:88416846:T:A	donor_loss	1.0000
14:88427193:GAAAT:G	donor_gain	1.0000
14:88427197:T:G	donor_gain	1.0000
14:88427197:T:TG	donor_gain	1.0000
14:88429335:ATT:A	acceptor_gain	1.0000
14:88429337:T:A	acceptor_gain	1.0000
14:88429340:A:AG	acceptor_gain	1.0000
14:88429341:T:G	acceptor_gain	1.0000
14:88429342:CCCCA:C	acceptor_loss	1.0000
14:88429343:CCCAG:C	acceptor_loss	1.0000
14:88429344:CCA:C	acceptor_loss	1.0000
14:88429345:CAGGC:C	acceptor_loss	1.0000
14:88429346:A:AG	acceptor_gain	1.0000
14:88429346:A:T	acceptor_loss	1.0000
14:88429347:G:GA	acceptor_loss	1.0000
14:88429347:G:GG	acceptor_gain	1.0000
14:88429347:GGC:G	acceptor_gain	1.0000
14:88429459:CCAAG:C	donor_loss	1.0000
14:88429460:CAAG:C	donor_loss	1.0000

AlphaMissense

3956 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:88393483:C:A	A62D	0.997
14:88426577:T:C	F240L	0.996
14:88426579:C:A	F240L	0.996
14:88426579:C:G	F240L	0.996
14:88393482:G:C	A62P	0.995
14:88416726:G:C	R85P	0.995
14:88396182:A:C	S73R	0.994
14:88396184:C:A	S73R	0.994
14:88396184:C:G	S73R	0.994
14:88393461:C:G	H55D	0.992
14:88391449:A:C	S30R	0.991
14:88391451:T:A	S30R	0.991
14:88391451:T:G	S30R	0.991
14:88426617:T:A	L253Q	0.991
14:88396194:A:C	S77R	0.990
14:88396196:C:A	S77R	0.990
14:88396196:C:G	S77R	0.990
14:88426578:T:C	F240S	0.990
14:88426584:C:A	P242H	0.989
14:88433161:T:C	F370S	0.989
14:88393441:T:A	V48D	0.988
14:88393464:T:G	Y56D	0.988
14:88433160:T:C	F370L	0.988
14:88433162:C:A	F370L	0.988
14:88433162:C:G	F370L	0.988
14:88437866:T:C	L415P	0.988
14:88393487:A:C	K63N	0.987
14:88393487:A:T	K63N	0.987
14:88426593:T:C	L245S	0.987
14:88426634:T:G	Y259D	0.987

dbSNP variants (sampled 300 via entrez): RS1000002955 (14:88408034 G>C), RS1000047815 (14:88396537 T>A), RS1000058632 (14:88412708 G>T), RS1000075430 (14:88416555 T>C,G), RS1000087197 (14:88457233 TTAAAG>T), RS1000089473 (14:88441107 T>C), RS1000167783 (14:88404585 C>T), RS1000217444 (14:88454850 T>C), RS1000281815 (14:88398450 A>T), RS1000286188 (14:88402690 A>G), RS1000334485 (14:88465954 T>C), RS1000402543 (14:88446401 T>C,G), RS1000462700 (14:88420884 G>A), RS1000488003 (14:88409596 C>T), RS1000513952 (14:88470404 A>C,G)

Disease associations

OMIM: gene MIM:609868 | disease phenotypes: MIM:604232, MIM:204000, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber congenital amaurosis 3	Definitive	Autosomal recessive
severe early-childhood-onset retinal dystrophy	Supportive	Autosomal recessive
Leber congenital amaurosis	Supportive	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
inherited retinal dystrophy	Definitive	AR

Mondo (7): Leber congenital amaurosis 3 (MONDO:0011415), inherited retinal dystrophy (MONDO:0019118), Leber congenital amaurosis (MONDO:0018998), retinitis pigmentosa 94, variable age at onset (MONDO:0800328), retinitis pigmentosa (MONDO:0019200), optic atrophy (MONDO:0003608), severe early-childhood-onset retinal dystrophy (MONDO:0009549)

Orphanet (3): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber congenital amaurosis (Orphanet:65), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

72 total (30 of 72 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000533	Chorioretinal atrophy
HP:0000540	Hypermetropia
HP:0000541	Retinal detachment
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000550	Undetectable electroretinogram
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000572	Visual loss
HP:0000577	Exotropia
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000622	Blurred vision
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000729	Autistic behavior
HP:0000842	Hyperinsulinemia
HP:0001103	Abnormal macular morphology
HP:0001105	Retinal atrophy

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000905_5	Information processing speed	3.000000e-06
GCST002097_40	Coronary artery calcification	3.000000e-06
GCST006916_4	Attention deficit hyperactivity disorder	6.000000e-07
GCST007001_8	Cerebrospinal AB1-42 levels in normal cognition	5.000000e-07
GCST008058_147	Estimated glomerular filtration rate	1.000000e-14
GCST008059_171	Estimated glomerular filtration rate	2.000000e-13
GCST008747_171	Estimated glomerular filtration rate	3.000000e-07
GCST008747_25	Estimated glomerular filtration rate	7.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004363	information processing speed
EFO:0004723	coronary artery calcification
EFO:0004670	beta-amyloid 1-42 measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C565814	Leber Congenital Amaurosis 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
ochratoxin A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, 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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Decitabine	affects expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Coumestrol	affects cotreatment, decreases expression	1
Cytarabine	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Melphalan	decreases expression	1
Methyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

287 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
NCT05244304	PHASE3	COMPLETED	Phase 3, Randomized, Placebo-Controlled Study of Tinlarebant to Explore Safety and Efficacy in Adolescent Stargardt Disease
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
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
NCT04489511	PHASE2	COMPLETED	Study of STG-001 in Subjects With Stargardt Disease
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)