NRL (neural retina leucine zipper)

Gene

• Entrez ID: 4901
• Gene name: Neural retina leucine zipper
• Gene symbol: NRL
• Synonyms (NCBI Gene): D14S46E, NRL-MAF, RP27
• Chromosome: 14
• Chromosome location: 14q11.2-q12
• Summary: 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 as

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894459	A>T	Pathogenic	Missense variant, intron variant, coding sequence variant
rs104894463	A>G	Pathogenic	Missense variant, coding sequence variant
rs397514516	A>G	Pathogenic	Coding sequence variant, intron variant, missense variant
rs527236087	A>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs762991211	G>A	Pathogenic	Stop gained, intron variant, coding sequence variant
rs763191889	->G	Pathogenic	Intron variant, frameshift variant, coding sequence variant
rs794727281	G>A	Pathogenic	Intron variant, coding sequence variant, missense variant
rs901811301	G>A	Pathogenic	Coding sequence variant, stop gained
rs1566560531	G>C	Likely-pathogenic	Stop gained, coding sequence variant, intron variant
rs1566561006	G>-,GG	Pathogenic	Coding sequence variant, intron variant, frameshift variant
rs1594246708	->CCGCAGCC	Pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT527429	hsa-miR-892a	PAR-CLIP	22012620
MIRT527428	hsa-miR-216b-3p	PAR-CLIP	22012620
MIRT527427	hsa-miR-1306-5p	PAR-CLIP	22012620
MIRT527426	hsa-miR-6760-3p	PAR-CLIP	22012620
MIRT527425	hsa-miR-1208	PAR-CLIP	22012620
MIRT527424	hsa-miR-361-3p	PAR-CLIP	22012620
MIRT527423	hsa-miR-2116-3p	PAR-CLIP	22012620
MIRT527422	hsa-miR-6879-3p	PAR-CLIP	22012620
MIRT527421	hsa-miR-597-5p	PAR-CLIP	22012620
MIRT527420	hsa-miR-197-3p	PAR-CLIP	22012620
MIRT527419	hsa-miR-181b-2-3p	PAR-CLIP	22012620
MIRT527418	hsa-miR-181b-3p	PAR-CLIP	22012620
MIRT527417	hsa-miR-4420	PAR-CLIP	22012620
MIRT527416	hsa-miR-653-3p	PAR-CLIP	22012620
MIRT527415	hsa-miR-4691-5p	PAR-CLIP	22012620
MIRT527414	hsa-miR-6792-3p	PAR-CLIP	22012620
MIRT527413	hsa-miR-592	PAR-CLIP	22012620
MIRT527429	hsa-miR-892a	PAR-CLIP	22012620
MIRT527428	hsa-miR-216b-3p	PAR-CLIP	22012620
MIRT527427	hsa-miR-1306-5p	PAR-CLIP	22012620
MIRT527426	hsa-miR-6760-3p	PAR-CLIP	22012620
MIRT527425	hsa-miR-1208	PAR-CLIP	22012620
MIRT527424	hsa-miR-361-3p	PAR-CLIP	22012620
MIRT527423	hsa-miR-2116-3p	PAR-CLIP	22012620
MIRT527422	hsa-miR-6879-3p	PAR-CLIP	22012620
MIRT527421	hsa-miR-597-5p	PAR-CLIP	22012620
MIRT527420	hsa-miR-197-3p	PAR-CLIP	22012620
MIRT527419	hsa-miR-181b-2-3p	PAR-CLIP	22012620
MIRT527418	hsa-miR-181b-3p	PAR-CLIP	22012620
MIRT527417	hsa-miR-4420	PAR-CLIP	22012620
MIRT527416	hsa-miR-653-3p	PAR-CLIP	22012620
MIRT527415	hsa-miR-4691-5p	PAR-CLIP	22012620
MIRT527414	hsa-miR-6792-3p	PAR-CLIP	22012620
MIRT527413	hsa-miR-592	PAR-CLIP	22012620
MIRT1194231	hsa-miR-1178	CLIP-seq
MIRT1194232	hsa-miR-1184	CLIP-seq
MIRT1194233	hsa-miR-1207-3p	CLIP-seq
MIRT1194234	hsa-miR-1207-5p	CLIP-seq
MIRT1194235	hsa-miR-1266	CLIP-seq
MIRT1194236	hsa-miR-1301	CLIP-seq
MIRT1194237	hsa-miR-1825	CLIP-seq
MIRT1194238	hsa-miR-197	CLIP-seq
MIRT1194239	hsa-miR-3135	CLIP-seq
MIRT1194240	hsa-miR-3153	CLIP-seq
MIRT1194241	hsa-miR-3663-3p	CLIP-seq
MIRT1194242	hsa-miR-3689a-3p	CLIP-seq
MIRT1194243	hsa-miR-3689c	CLIP-seq
MIRT1194244	hsa-miR-3689d	CLIP-seq
MIRT1194245	hsa-miR-3929	CLIP-seq
MIRT1194246	hsa-miR-4418	CLIP-seq
MIRT1194247	hsa-miR-4419b	CLIP-seq
MIRT1194248	hsa-miR-4478	CLIP-seq
MIRT1194249	hsa-miR-4518	CLIP-seq
MIRT1194250	hsa-miR-4525	CLIP-seq
MIRT1194251	hsa-miR-4646-5p	CLIP-seq
MIRT1194252	hsa-miR-4660	CLIP-seq
MIRT740170	hsa-miR-4667-3p	CLIP-seq
MIRT1194253	hsa-miR-4668-5p	CLIP-seq
MIRT1194254	hsa-miR-4716-3p	CLIP-seq
MIRT1194255	hsa-miR-4722-5p	CLIP-seq
MIRT1194256	hsa-miR-4728-5p	CLIP-seq
MIRT1194257	hsa-miR-4736	CLIP-seq
MIRT1194258	hsa-miR-4738-3p	CLIP-seq
MIRT1194259	hsa-miR-4763-3p	CLIP-seq
MIRT740171	hsa-miR-4772-3p	CLIP-seq
MIRT1194260	hsa-miR-5047	CLIP-seq
MIRT1194261	hsa-miR-509-3-5p	CLIP-seq
MIRT1194262	hsa-miR-509-5p	CLIP-seq
MIRT1194263	hsa-miR-542-3p	CLIP-seq
MIRT740172	hsa-miR-558	CLIP-seq
MIRT1194264	hsa-miR-645	CLIP-seq
MIRT2056373	hsa-miR-3152-3p	CLIP-seq
MIRT2056374	hsa-miR-3919	CLIP-seq
MIRT2056375	hsa-miR-5095	CLIP-seq
MIRT2056376	hsa-miR-552	CLIP-seq
MIRT2056377	hsa-miR-570	CLIP-seq
MIRT2284921	hsa-miR-1254	CLIP-seq
MIRT2284922	hsa-miR-2110	CLIP-seq
MIRT2284923	hsa-miR-3116	CLIP-seq
MIRT2284924	hsa-miR-3144-5p	CLIP-seq
MIRT2284925	hsa-miR-3150a-3p	CLIP-seq
MIRT2284926	hsa-miR-3175	CLIP-seq
MIRT2284927	hsa-miR-3191	CLIP-seq
MIRT2284928	hsa-miR-4652-5p	CLIP-seq
MIRT1194258	hsa-miR-4738-3p	CLIP-seq
MIRT2284929	hsa-miR-4786-5p	CLIP-seq
MIRT2284930	hsa-miR-635	CLIP-seq
MIRT2284931	hsa-miR-665	CLIP-seq
MIRT2284932	hsa-miR-939	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	8552602, 17335001
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	8552602
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	17335001
GO:0003677	Function	DNA binding	IEA
GO:0003677	Function	DNA binding	TAS	1729696
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005515	Function	Protein binding	IPI	10887186, 15028672, 23956131
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	11477108, 17335001
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	TAS	8939891
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IDA	11477108
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0007601	Process	Visual perception	IEA
GO:0007601	Process	Visual perception	TAS	1729696
GO:0010628	Process	Positive regulation of gene expression	IEA
GO:0043522	Function	Leucine zipper domain binding	IPI	10887186
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	8552602
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	17335001, 21981118
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	TAS	8939891
GO:0046548	Process	Retinal rod cell development	IBA
GO:0046548	Process	Retinal rod cell development	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536
GO:1990841	Function	Promoter-specific chromatin binding	IEA

Other IDs

• MIM: 162080
• HGNC: 8002
• e!Ensembl: ENSG00000129535

Protein

• UniProt ID: P54845
• Protein name: Neural retina-specific leucine zipper protein (NRL)
• Protein function: Acts as a transcriptional activator which regulates the expression of several rod-specific genes, including RHO and PDE6B (PubMed:21981118). Also functions as a transcriptional coactivator, stimulating transcription mediated by the transcription
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08383	Maf_N	67 → 101	Maf N-terminal region	Family
  PF03131	bZIP_Maf	132 → 223	bZIP Maf transcription factor	Coiled-coil

• Tissue specificity: TISSUE SPECIFICITY: Expressed in the brain and the retina (PubMed:11477108). Expressed strongly in rod and cone cells (at protein level) (PubMed:11477108). {ECO:0000269|PubMed:11477108}.
• Sequence:

  MALPPSPLAMEYVNDFDLMKFEVKREPSEGRPGPPTASLGSTPYSSVPPSPTFSEPGMVG
  ATEGTRPGLEELYWLATLQQQLGAGEALGLSPEEAMELLQGQGPVPVDGPHGYYPGSPEE
  TGAQHVQLAERFSDAALVSMSVRELNRQLRGCGRDEALRLKQRRRTLKNRGYAQACRSKR
  LQQRRGLEAERARLAAQLDALRAEVARLARERDLYKARCDRLTSSGPGSGDPSHLFL

• Sequence length: 237

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Enhanced S-cone syndrome	Likely pathogenic; Pathogenic	rs762991211	RCV000408517	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
ENHANCED S-CONE SYNDROME 2	Pathogenic; Likely pathogenic	rs763191889, rs104894463	RCV005861019 RCV005861020	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinal dystrophy	Likely pathogenic; Pathogenic	rs2036353653, rs104894459, rs1350116482, rs764142151, rs1566561006, rs768178406, rs2036353932	RCV004815501 RCV004817194 RCV003889645 RCV003889646 RCV004817919 RCV001073789 RCV003890340 RCV003887951	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinitis pigmentosa	Likely pathogenic; Pathogenic	rs527236087, rs1594246708, rs2138875137	RCV000132657 RCV001003097 RCV001535429	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis pigmentosa 27	Likely pathogenic; Pathogenic	rs2036353653, rs2036279881, rs794727281, rs104894459, rs763191889, rs762991211, rs1566561006, rs1566560531	RCV001376379 RCV001799579 RCV001376429 RCV000015086 RCV002476969 RCV001782861 RCV000678586 RCV000761516 RCV005648093	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NRL-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINAL DEGENERATION	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINAL DEGENERATION, AUTOSOMAL RECESSIVE, CLUMPED PIGMENT TYPE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINITIS PIGMENTOSA 1	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Retinitis Pigmentosa, Dominant	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	29935374		★☆☆☆☆ Found in Text Mining only
Adult Medulloblastoma	Medulloblastoma	BEFREE	29533784		★☆☆☆☆ Found in Text Mining only
Amaurosis congenita of Leber type 1	Leber congenital amaurosis	Pubtator	35693422	Associate	★☆☆☆☆ Found in Text Mining only
Amaurosis congenita of Leber, type 1	Leber congenital amaurosis	BEFREE	12552256		★☆☆☆☆ Found in Text Mining only
Atrophoderma maculatum	Anetoderma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	25472540		★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Childhood Medulloblastoma	Medulloblastoma	BEFREE	29533784		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	31184445		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	30509242, 30800188		★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of penis	Congenital Hypoplasia Of Penis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	31639404		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetic Retinopathy	Diabetic retinopathy	Pubtator	37318461	Associate	★☆☆☆☆ Found in Text Mining only
Disorder of eye	Disorder Of Eye	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Enhanced S-Cone Syndrome	Enhanced S-Cone Syndrome	BEFREE	15459973, 21659555, 27732723, 29385733, 29518905		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Enhanced S-Cone Syndrome	Enhanced S-Cone Syndrome	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Glaucoma	Glaucoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	29076002		★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Keratoconus	Keratoconus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leber Congenital Amaurosis	Leber congenital amaurosis	Pubtator	12552256, 20513135	Associate	★☆☆☆☆ Found in Text Mining only
Leber Congenital Amaurosis	Leber Congenital Amaurosis	BEFREE	20513135		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	25472540		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	BEFREE	29533784		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy, Oculopharyngeal	Oculopharyngeal Muscular Dystrophy	BEFREE	27732723, 28590779		★☆☆☆☆ Found in Text Mining only
Myopathies Nemaline	Nemaline myopathy	Pubtator	15591106	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29935374		★☆☆☆☆ Found in Text Mining only
Nyctalopia	Nyctalopia	CTD_human_DG	12796249, 15591106		★☆☆☆☆ Found in Text Mining only
Nyctalopia	Nyctalopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	HPO_DG			★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripapillary chorioretinal atrophy	Peripapillary chorioretinal atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Phosphoenolpyruvate Carboxykinase Deficiency, Mitochondrial	Phosphoenolpyruvate carboxykinase deficiency	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Retinal Degeneration	Retinal degeneration	Pubtator	15591106, 17356515	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Retinal Degeneration Autosomal Recessive Clumped Pigment Type	Retinal degeneration	Pubtator	39766861	Associate	★☆☆☆☆ Found in Text Mining only
Retinal Degeneration, Autosomal Recessive, Clumped Pigment Type	Retinal Degeneration	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Retinal Diseases	Retinal Diseases	BEFREE	12552256, 17335001, 9344665		★☆☆☆☆ Found in Text Mining only
Retinal Diseases	Retinal detachment	Pubtator	35693422	Associate	★☆☆☆☆ Found in Text Mining only
Retinal Dystrophies	Retinal Dystrophy	BEFREE	11039579, 28590779		★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	CTD_human_DG	10192380, 12796249		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	BEFREE	11385710, 11879142, 12796249, 17335001, 19933183, 21981118, 28291770		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis pigmentosa	Pubtator	12552256, 15591106, 15994872, 27081294, 32081919, 35693422, 39766861	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	LHGDN	17335001		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis pigmentosa	Retinitis Pigmentosa	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	GENOMICS_ENGLAND_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
RETINITIS PIGMENTOSA 27	Retinitis Pigmentosa	UNIPROT_DG	10192380, 11385710, 11879142, 15591106, 15994872, 17335001, 21981118, 22334370		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RETINITIS PIGMENTOSA 27	Retinitis Pigmentosa	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RETINITIS PIGMENTOSA 27	Retinitis Pigmentosa	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RETINITIS PIGMENTOSA 27	Retinitis Pigmentosa	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RHYNS syndrome	Rhyns syndrome	Pubtator	35693422	Associate	★☆☆☆☆ Found in Text Mining only
Rod-Cone Dystrophy	Rod-cone dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only