NRL

Summary

NRL (neural retina leucine zipper, HGNC:8002) is a protein-coding gene on chromosome 14q11.2-q12, encoding Neural retina-specific leucine zipper protein (P54845). Acts as a transcriptional activator which regulates the expression of several rod-specific genes, including RHO and PDE6B.

This gene encodes a basic motif-leucine zipper transcription factor of the Maf subfamily. The encoded protein is conserved among vertebrates and is a critical intrinsic regulator of photoceptor development and function. Mutations in this gene have been associated with retinitis pigmentosa and retinal degenerative diseases.

Source: NCBI Gene 4901 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 27 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 487 total — 20 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 57
• Transcription factor: yes — 20 downstream targets (CollecTRI)
• MANE Select transcript: NM_001354768

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8002
Approved symbol	NRL
Name	neural retina leucine zipper
Location	14q11.2-q12
Locus type	gene with protein product
Status	Approved
Aliases	D14S46E, RP27, NRL-MAF
Ensembl gene	ENSG00000129535
Ensembl biotype	protein_coding
OMIM	162080
Entrez	4901

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000396995, ENST00000396997, ENST00000397002, ENST00000558280, ENST00000560550, ENST00000561028, ENST00000905081, ENST00000905082, ENST00000905083, ENST00000905084, ENST00000933893, ENST00000947384

RefSeq mRNA: 4 — MANE Select: NM_001354768 NM_001354768, NM_001354769, NM_001354770, NM_006177

CCDS: CCDS9608

Canonical transcript exons

ENST00000561028 — 3 exons

Exon	Start	End
ENSE00000889335	24082468	24082875
ENSE00002539633	24114722	24114949
ENSE00002555259	24078662	24081568

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 75.70.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9263 / max 766.0078, expressed in 600 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142528	0.8343	458
142524	0.7200	15
142526	0.2350	109
142527	0.0825	35
142522	0.0365	8
142525	0.0101	5
142523	0.0079	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.23	gold quality
cortical plate	UBERON:0005343	70.66	gold quality
right lobe of liver	UBERON:0001114	70.59	gold quality
granulocyte	CL:0000094	70.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	69.78	gold quality
prefrontal cortex	UBERON:0000451	69.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.14	gold quality
apex of heart	UBERON:0002098	69.12	gold quality
adult mammalian kidney	UBERON:0000082	68.74	gold quality
amygdala	UBERON:0001876	68.72	gold quality
right adrenal gland	UBERON:0001233	68.68	gold quality
temporal lobe	UBERON:0001871	68.68	gold quality
nucleus accumbens	UBERON:0001882	68.48	gold quality
substantia nigra	UBERON:0002038	68.38	gold quality
putamen	UBERON:0001874	68.37	gold quality
left adrenal gland	UBERON:0001234	68.22	gold quality
gastrocnemius	UBERON:0001388	68.21	gold quality
muscle of leg	UBERON:0001383	67.84	gold quality
frontal cortex	UBERON:0001870	67.75	gold quality
left adrenal gland cortex	UBERON:0035825	67.70	gold quality
caudate nucleus	UBERON:0001873	67.67	gold quality
Ammon’s horn	UBERON:0001954	67.59	gold quality
right adrenal gland cortex	UBERON:0035827	67.38	gold quality
anterior cingulate cortex	UBERON:0009835	67.12	gold quality
cerebral cortex	UBERON:0000956	66.90	gold quality
adrenal gland	UBERON:0002369	66.68	gold quality
liver	UBERON:0002107	66.61	gold quality
hypothalamus	UBERON:0001898	66.42	gold quality
heart left ventricle	UBERON:0002084	66.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	7883.10
E-GEOD-137537	yes	6883.59
E-MTAB-7316	yes	72.93
E-ANND-3	no	4.04

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

20 targets.

Target	Regulation
ADAM2
ALDH7A1
CISH
CRYZ
FSCN2	Activation
GRB10
KCNV2
KNTC1
MEF2C	Unknown
NR2E3	Activation
NRL
OPN1SW
PAX6
PDE6A	Unknown
PDE6B	Unknown
PIAS3
PPP2R5C
RBP3	Repression
RHO	Repression
SAG

JASPAR motifs

Motif	Name	Family
MA0842.1	NRL	Maf-related
MA0842.2	NRL	Maf-related
MA0842.3	NRL	Maf-related

JASPAR matrix evidence (PMIDs): PMID:8552602

Upstream regulators (CollecTRI, top): CRX, JUN, NR1D1, NR2E3, NR2F1, NRL, OTX2, RORB

Literature-anchored findings (GeneRIF, showing 23)

• six isoforms of NRL (29-35 kDa) are generated by phosphorylation and expressed specifically in the mammalian retina. (PMID:11477108)
• The disease caused by NRL mutations found in this study appears to be more severe (PMID:11879142)
• Mutation screening of patients with Leber Congenital Amaurosis or the enhanced S-Cone Syndrome reveals a lack of sequence variations in the NRL gene. (PMID:12552256)
• the function of NRL is modulated by its interaction with specific repressor proteins, related to cross-talk between signaling pathways in the retina (PMID:12566383)
• The NRL Ser50Thr mutation is associated with selective loss of scotopic function before age 20 years. With time, however, the photopic system becomes affected, leading to loss of the photopic visual field and of visual acuity. (PMID:12796249)
• both Nrl and Crx are required for full transcriptional activity of the PDE6A gene (PMID:15001570)
• the function of NRL-MTD is to activate transcription by recruiting or stabilizing TBP (and consequently other components of the general transcription complex) at the promoter of target genes (PMID:15328344)
• Mutation analysis of the NRL gene, in patients with Enhanced S Cone Syndrome (PMID:15459973)
• an unusual clinical phenotype in humans with loss-of-function mutations in NRL (PMID:15591106)
• signaling by RA via RA receptors regulates the expression of NRL, providing a framework for delineating early steps in photoreceptor cell fate determination (PMID:16854989)
• Gain-of-function mutations in the NRL gene cause autosomal dominant retinitis pigmentosa[RP] while loss-of-function mutations cause autosomal recessive RP. Differential phosphorylation of NRL fine-tunes its transcriptional regulatory activity. (PMID:17335001)
• In this study, NR2E3 mutations were found to be responsible for approximately 2.9% of overall retinitis pigmentosa (RP) in Chinese patients, NRL was not associated with RP. (PMID:19933183)
• Studies suggest an important role of sumoylation in fine-tuning the activity of NRL and thereby incorporating yet another layer of control in gene regulatory networks involved in photoreceptor development and homeostasis. (PMID:20551322)
• This novel p.M96T mutant activated the RHO promoter more intensely than did wild-type NRL in a family with autosomal dominant retinitis pigmentosa. (PMID:21981118)
• In another family a variant, p.M96T in the NRL gene was detected as a retinitis pigmentosa-causing mutation. (PMID:23534816)
• The c.146 C>T mutation in NRL gene causes autosomal dominant retinitis pigmentosa for this family. (PMID:27081294)
• This report expands the spectrum of NRL recessive mutations, as well as the genetic spectrum of ESCS, and indicates a new syndrome of OPMD with an ESCS-like phenotype. (PMID:27732723)
• We identified a novel NRL mutation (c.147_149del, p.Ser50del) leading to adRP in a Chinese family with retinitis pigmenntosa. (PMID:28106895)
• investigated the prevalence of the NRL mutation among Bukhara Jews with oculopharyngeal muscular dystrophy (OPMD) (PMID:28590779)
• that two photoreceptor-specific transcription factors, NRL and CRX, are master regulators of this program and are required for tumor maintenance in this subgroup (PMID:29533784)
• Investigating cone photoreceptor development using patient-derived NRL null retinal organoids. (PMID:32081919)
• NRL(-/-) gene edited human embryonic stem cells generate rod-deficient retinal organoids enriched in S-cone-like photoreceptors. (PMID:33400844)
• Novel homozygous mutations in the transcription factor NRL cause non-syndromic retinitis pigmentosa. (PMID:35693422)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrl	ENSDARG00000100466
mus_musculus	Nrl	ENSMUSG00000040632
rattus_norvegicus	Nrl	ENSRNOG00000018528
drosophila_melanogaster	tj	FBGN0000964
drosophila_melanogaster	maf-S	FBGN0034534
caenorhabditis_elegans	maf-1	WBGENE00077521

Paralogs (6): MAF (ENSG00000178573), MAFA (ENSG00000182759), MAFF (ENSG00000185022), MAFG (ENSG00000197063), MAFK (ENSG00000198517), MAFB (ENSG00000204103)

Protein

Protein identifiers

Neural retina-specific leucine zipper protein — P54845 (reviewed: P54845)

All UniProt accessions (2): P54845, H0YNW2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional activator which regulates the expression of several rod-specific genes, including RHO and PDE6B. Also functions as a transcriptional coactivator, stimulating transcription mediated by the transcription factor CRX and NR2E3. Binds to the rhodopsin promoter in a sequence-specific manner.

Subunit / interactions. Interacts with FIZ1; this interaction represses transactivation. Interacts (via the leucine-zipper domain) with CRX.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in the brain and the retina. Expressed strongly in rod and cone cells (at protein level).

Post-translational modifications. Phosphorylated. Disumoylated at Lys-20. Sumoylation modulates the transcriptional activity of NRL on RHO and NR2E3 promoters, and is required for normal rod differentiation.

Disease relevance. Retinitis pigmentosa 27 (RP27) [MIM:613750] 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. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry. Retinal degeneration autosomal recessive clumped pigment type (RDCP) [MIM:613750] A retinopathy characterized by night blindness since early childhood, consistent with a severe reduction in rod function. Color vision is normal although there is a relatively enhanced function of short-wavelength-sensitive cones in the macula. Signs of retinal degeneration and clusters of clumped pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium are present. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The minimal transactivation domain (MTD) is conserved across the MAF family, it may activate transcription by recruiting TBP and associated factors at the promoters of target genes.

Similarity. Belongs to the bZIP family.

Isoforms (2)

UniProt ID	Names	Canonical?
P54845-1	1	yes
P54845-2	2

RefSeq proteins (4): NP_001341697, NP_001341698, NP_001341699, NP_006168 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004826	bZIP_Maf	Domain
IPR004827	bZIP	Domain
IPR008917	TF_DNA-bd_sf	Homologous_superfamily
IPR013592	Maf_TF_N	Domain
IPR024874	Transcription_factor_Maf_fam	Family
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF03131, PF08383

UniProt features (22 total): sequence variant 13, region of interest 4, cross-link 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54845-F1	72.42	0.40

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 (2): 20, 24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 213 (showing top): MODULE_255, RORA1_01, NKX25_02, MODULE_317, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, LHX3_01, chr14q12, PUJANA_CHEK2_PCC_NETWORK, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EYE_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_PHOTORECEPTOR_CELL_DEVELOPMENT, GOBP_CAMERA_TYPE_EYE_PHOTORECEPTOR_CELL_DIFFERENTIATION, ATGCTGG_MIR338

GO Biological Process (6): regulation of transcription by RNA polymerase II (GO:0006357), visual perception (GO:0007601), positive regulation of gene expression (GO:0010628), positive regulation of transcription by RNA polymerase II (GO:0045944), retinal rod cell development (GO:0046548), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), leucine zipper domain binding (GO:0043522), sequence-specific double-stranded DNA binding (GO:1990837), promoter-specific chromatin binding (GO:1990841), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of gene expression	2
regulation of transcription by RNA polymerase II	2
sensory perception of light stimulus	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of DNA-templated transcription	1
eye photoreceptor cell development	1
retinal rod cell differentiation	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
LRR domain binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
chromatin binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRL	CRX	O43186	986
NRL	NR2E3	Q9Y5X4	936
NRL	RHO	P08100	871
NRL	FIZ1	Q96SL8	846
NRL	FSCN2	O14926	812
NRL	RPE65	Q16518	798
NRL	PDE6B	P35913	779
NRL	RP9	Q8TA86	738
NRL	PRPF31	Q8WWY3	734
NRL	IMPG2	Q9BZV3	733
NRL	PDE6A	P16499	731
NRL	GNAT1	P11488	729
NRL	EYS	Q5T1H1	727
NRL	PRPF3	O43395	726
NRL	IMPDH1	P20839	720

IntAct

10 interactions, top by confidence:

A	B	Type	Score
NRL	CRX	psi-mi:“MI:0915”(physical association)	0.650
CRX	NRL	psi-mi:“MI:0915”(physical association)	0.650
NRL	Rax	psi-mi:“MI:0915”(physical association)	0.400
	NRL	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (17): NRL (Affinity Capture-Western), OPTN (Affinity Capture-Western), NRL (Co-localization), NRL (FRET), NRL (FRET), NR2E3 (FRET), NRL (Biochemical Activity), NRL (Biochemical Activity), FIZ1 (Two-hybrid), FIZ1 (Reconstituted Complex), CRX (Two-hybrid), CRX (Reconstituted Complex), NRL (Two-hybrid), NRL (Positive Genetic), NRL (Biochemical Activity)

ESM2 similar proteins: A5PJV0, A5PKJ4, A7YY73, O15525, O42290, O42406, O54790, O54791, O57337, O57342, O60675, O73916, O93307, O95343, O95475, P10360, P13097, P35428, P50538, P54845, P54846, Q01068, Q01069, Q04666, Q13164, Q14469, Q14582, Q2KIN4, Q3ZBG4, Q5FWS6, Q5TA89, Q5ZK92, Q60948, Q61827, Q62232, Q62233, Q674X7, Q69ZS8, Q6P730, Q76MX4

Diamond homologs: A3KMR8, A5PJV0, A7YY73, A7Z017, D3ZNT6, O15525, O42290, O54790, O54791, O57342, O60675, O75444, P23091, P54841, P54842, P54843, P54844, P54845, P54846, Q0V9K1, Q2PFS4, Q4U1U2, Q504L8, Q61827, Q6DE84, Q76MX4, Q789F3, Q8CF90, Q8NHW3, Q90370, Q90595, Q90596, Q90888, Q90889, Q98UK4, Q98UK5, Q9ULX9, Q9Y5Q3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NRL	“down-regulates quantity by repression”	RBP3	“transcriptional regulation”
NRL	“down-regulates quantity by repression”	RHO	“transcriptional regulation”
FIZ1	“up-regulates activity”	NRL	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	11
Uncertain significance	302
Likely benign	105
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1369271	NM_001354768.3(NRL):c.21_24del (p.Leu8fs)	Pathogenic
1395570	NM_001354768.3(NRL):c.348del (p.Ser117fs)	Pathogenic
14042	NM_001354768.3(NRL):c.148T>A (p.Ser50Thr)	Pathogenic
14043	NM_001354768.3(NRL):c.223dup (p.Leu75fs)	Pathogenic
1452628	NM_001354768.3(NRL):c.15dup (p.Ser6fs)	Pathogenic
1515397	NM_001354768.3(NRL):c.459_477dup (p.Leu160fs)	Pathogenic
154806	GRCh38/hg38 14q11.2-12(chr14:23984065-25374494)x1	Pathogenic
1919840	NM_001354768.3(NRL):c.76dup (p.Glu26fs)	Pathogenic
1976736	NM_001354768.3(NRL):c.474_475insA (p.Arg159fs)	Pathogenic
1996526	NM_001354768.3(NRL):c.381+1G>A	Pathogenic
3721479	NM_001354768.3(NRL):c.235C>T (p.Gln79Ter)	Pathogenic
3769791	NM_001354768.3(NRL):c.146C>T (p.Pro49Leu)	Pathogenic
4278921	NRL, ARG170SER	Pathogenic
4278922	NRL, 1-BP DEL, NT654	Pathogenic
4278924	NRL, 1-BP DEL, 22C	Pathogenic
4722074	NM_001354768.3(NRL):c.67del (p.Glu22_Val23insTer)	Pathogenic
560472	NM_001354768.3(NRL):c.104dup (p.Thr36fs)	Pathogenic
812356	NM_001354768.3(NRL):c.444_445insGCTGCGGG (p.Leu149fs)	Pathogenic
938373	NM_001354768.3(NRL):c.151C>A (p.Pro51Thr)	Pathogenic
995879	NM_001354768.3(NRL):c.238C>T (p.Gln80Ter)	Pathogenic
14044	NM_001354768.3(NRL):c.479T>C (p.Leu160Pro)	Likely pathogenic
143133	NM_001354768.3(NRL):c.23del (p.Leu8fs)	Likely pathogenic
3028276	NM_001354768.3(NRL):c.371A>C (p.Gln124Pro)	Likely pathogenic
3250313	NM_001354768.3(NRL):c.452_459dup (p.Arg154fs)	Likely pathogenic
3767337	NM_001354768.3(NRL):c.152C>G (p.Pro51Arg)	Likely pathogenic
3780043	NM_001354768.3(NRL):c.22del (p.Leu8fs)	Likely pathogenic
4291979	NM_001354768.3(NRL):c.147_149del (p.Ser50del)	Likely pathogenic
4849279	NM_004563.4(PCK2):c.652_653del (p.Leu218fs)	Likely pathogenic
559132	NM_004563.4(PCK2):c.451_452dup (p.Met152fs)	Likely pathogenic
559134	NM_004563.4(PCK2):c.457del (p.Gln153fs)	Likely pathogenic

SpliceAI

2151 predictions. Top by Δscore:

Variant	Effect	Δscore
14:24081564:GCCAG:G	acceptor_gain	1.0000
14:24081565:CCAG:C	acceptor_gain	1.0000
14:24081565:CCAGC:C	acceptor_gain	1.0000
14:24081566:CAG:C	acceptor_gain	1.0000
14:24081566:CAGC:C	acceptor_gain	1.0000
14:24081567:AG:A	acceptor_gain	1.0000
14:24081569:C:A	acceptor_loss	1.0000
14:24081569:C:CC	acceptor_gain	1.0000
14:24081572:C:CT	acceptor_gain	1.0000
14:24081573:G:T	acceptor_gain	1.0000
14:24084518:A:AC	donor_gain	1.0000
14:24084519:C:CT	donor_gain	1.0000
14:24084519:CTT:C	donor_gain	1.0000
14:24097138:G:GC	donor_loss	1.0000
14:24097138:G:GG	donor_gain	1.0000
14:24097139:T:G	donor_loss	1.0000
14:24098676:AAGGT:A	donor_loss	1.0000
14:24098677:AGG:A	donor_loss	1.0000
14:24098678:GGT:G	donor_loss	1.0000
14:24098679:GT:G	donor_loss	1.0000
14:24098680:T:G	donor_loss	1.0000
14:24099167:G:GT	donor_gain	1.0000
14:24099549:A:AG	acceptor_gain	1.0000
14:24099549:AAT:A	acceptor_gain	1.0000
14:24099550:A:G	acceptor_gain	1.0000
14:24099551:T:TA	acceptor_gain	1.0000
14:24099553:CACA:C	acceptor_loss	1.0000
14:24099554:ACAG:A	acceptor_loss	1.0000
14:24099555:C:G	acceptor_gain	1.0000
14:24099555:CA:C	acceptor_loss	1.0000

AlphaMissense

1480 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:24081443:G:C	N169K	1.000
14:24081443:G:T	N169K	1.000
14:24081445:T:C	N169D	1.000
14:24081446:C:A	K168N	1.000
14:24081446:C:G	K168N	1.000
14:24081435:T:C	Y172C	0.999
14:24081436:A:G	Y172H	0.999
14:24081442:G:T	R170S	0.999
14:24081444:T:A	N169I	0.999
14:24081444:T:C	N169S	0.999
14:24081444:T:G	N169T	0.999
14:24081447:T:A	K168M	0.999
14:24081448:T:C	K168E	0.999
14:24081457:G:T	R165S	0.999
14:24081460:G:T	R164S	0.999
14:24081467:C:A	K161N	0.999
14:24081467:C:G	K161N	0.999
14:24081516:A:G	L145P	0.999
14:24081421:G:T	R177S	0.998
14:24081441:C:G	R170P	0.998
14:24081445:T:G	N169H	0.998
14:24081447:T:G	K168T	0.998
14:24081450:A:G	L167P	0.998
14:24081469:T:C	K161E	0.998
14:24081413:C:A	K179N	0.997
14:24081413:C:G	K179N	0.997
14:24081424:A:G	C176R	0.997
14:24081448:T:G	K168Q	0.996
14:24081468:T:A	K161M	0.996
14:24081504:A:G	L149P	0.996

dbSNP variants (sampled 300 via entrez): RS1000064420 (14:24106591 C>T), RS1000079743 (14:24116661 T>C,G), RS1000139909 (14:24113970 G>T), RS1000300047 (14:24105072 T>A), RS1000352017 (14:24104762 C>T), RS1000436978 (14:24080807 G>A), RS1000474004 (14:24078968 A>G), RS1000635926 (14:24103842 G>A), RS1000817259 (14:24106658 T>G), RS1000849859 (14:24104355 T>C,G), RS1000897770 (14:24109621 C>A,T), RS1000955429 (14:24116453 C>T), RS1001063675 (14:24093569 C>A), RS1001094305 (14:24093288 G>C), RS1001205680 (14:24109853 A>G,T)

Disease associations

OMIM: gene MIM:162080 | disease phenotypes: MIM:261650, MIM:613750, MIM:268000, MIM:621371, MIM:268100, MIM:136520

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 27	Definitive	Autosomal dominant
enhanced S-cone syndrome	Definitive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
retinitis pigmentosa 27	Definitive	AD

Mondo (10): phosphoenolpyruvate carboxykinase deficiency, mitochondrial (MONDO:0009864), retinitis pigmentosa 27 (MONDO:0013402), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa (MONDO:0019200), enhanced S-cone syndrome 2 (MONDO:0700386), enhanced S-cone syndrome (MONDO:0100288), phosphoenolpyruvate carboxykinase deficiency (MONDO:0017320), albinism (MONDO:0043209), foveal hypoplasia (MONDO:0044203), choroidal neovascularization (MONDO:0810000)

Orphanet (5): Phosphoenolpyruvate carboxykinase deficiency (Orphanet:2880), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Goldmann-Favre syndrome (Orphanet:53540), OBSOLETE: Phosphoenolpyruvate carboxykinase 2 deficiency (Orphanet:79317)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000533	Chorioretinal atrophy
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000550	Undetectable electroretinogram
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000580	Pigmentary retinopathy
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001133	Constriction of peripheral visual field
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0003829	Typified by incomplete penetrance
HP:0007401	Macular atrophy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003264_949	Post bronchodilator FEV1/FVC ratio	5.000000e-06
GCST003657_8	Attention deficit hyperactivity disorder symptom score	9.000000e-06
GCST010418_3	Liver fibrosis and steatohepatitis severity (MRI cT1 measure)	3.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0007860	ADHD symptom measurement
EFO:0006845	liver disease biomarker
EFO:0010821	liver fat measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D000417	Albinism	C11.270.040; C16.320.290.040; C16.320.565.100.102; C16.320.850.080; C17.800.621.440.102; C17.800.827.080; C18.452.648.100.102
D020256	Choroidal Neovascularization	C11.941.160.244; C23.550.589.500.145
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C564835	Enhanced S-Cone Syndrome (supp.)
C564890	Phosphoenolpyruvate Carboxykinase Deficiency, Mitochondrial (supp.)
C536654	Phosphoenolpyruvate carboxykinase deficiency (supp.)
C563526	Retinitis Pigmentosa 27 (supp.)

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
Benzo(a)pyrene	decreases expression, affects methylation	3
sodium arsenite	increases expression, affects methylation	2
bisphenol A	increases methylation	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Gefitinib	decreases expression	1
Sunitinib	decreases expression	1
Alitretinoin	increases expression	1
Cisplatin	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Rifampin	increases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B5ZI	WAe009-A-R	Embryonic stem cell	Female

Clinical trials (associated diseases)

259 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)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
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