CRX

cone-rod homeobox, the group of PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 19:47819779-47843330

Previous symbols: [ "CORD2" ]

Links

ENSG00000105392

∙ NCBI:1406 ∙ OMIM:602225 ∙ HGNC:2383 ∙ Uniprot:O43186 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Leber congenital amaurosis 7 (Definitive), mode of inheritance: AD
Leber congenital amaurosis 7 (Definitive), mode of inheritance: Semidominant
cone-rod dystrophy 2 (Definitive), mode of inheritance: AD
retinitis pigmentosa (Supportive), mode of inheritance: AD
cone-rod dystrophy (Supportive), mode of inheritance: AD
Leber congenital amaurosis (Supportive), mode of inheritance: AD
Leber congenital amaurosis 7 (Strong), mode of inheritance: AR
Leber congenital amaurosis 7 (Strong), mode of inheritance: AD
Leber congenital amaurosis 7 (Limited), mode of inheritance: AR
hereditary macular dystrophy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leber congenital amaurosis 7; Cone-rod dystrophy 2	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	9390563; 9390562; 9537410; 9931337; 12208271; 15531334; 20301475; 20301590; 20513135; 22960069

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRX gene.

Leber_congenital_amaurosis_7 (333 variants)
Cone-rod_dystrophy_2 (329 variants)
not_provided (80 variants)
Retinal_dystrophy (61 variants)
Retinitis_pigmentosa (33 variants)
Inborn_genetic_diseases (32 variants)
CRX-related_disorder (9 variants)
not_specified (8 variants)
Leber_congenital_amaurosis_1 (5 variants)
Stargardt_disease (3 variants)
Cone-rod_dystrophy (3 variants)
Autosomal_dominant_retinitis_pigmentosa (3 variants)
Benign_concentric_annular_macular_dystrophy (3 variants)
Leber_congenital_amaurosis (2 variants)
Macular_dystrophy (1 variants)
See_cases (1 variants)
Central_core_myopathy (1 variants)
Prostate_cancer (1 variants)
maculopathy (1 variants)
Usher_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRX gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000554.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar	1 clinvar	4 clinvar	76 clinvar	4 clinvar	86
missense	5 clinvar	17 clinvar	139 clinvar	17 clinvar		178
nonsense	9 clinvar	13 clinvar	2 clinvar			24
start loss			1			1
frameshift	66 clinvar	21 clinvar	13 clinvar			100
splice donor/acceptor (+/-2bp)	3 clinvar	2 clinvar	2 clinvar			7
Total	84	54	161	93	4

Highest pathogenic variant AF is 0.000016108308

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRX	protein_coding	protein_coding	ENST00000221996	3	23885

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.510	0.486	125741	0	5	125746	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.329	171	184	0.932	0.0000112	1900
Missense in Polyphen		52	60.794	0.85534		693
Synonymous	-0.690	92	84.0	1.10	0.00000557	662
Loss of Function	2.43	2	10.5	0.190	5.36e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000638	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with other transcription factors, such as NRL, RORB and RAX, to regulate photoreceptor cell-specific gene transcription. Essential for the maintenance of mammalian photoreceptors. {ECO:0000269|PubMed:10625658}.;
Disease: DISEASE: Cone-rod dystrophy 2 (CORD2) [MIM:120970]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:10887186, ECO:0000269|PubMed:9390563, ECO:0000269|PubMed:9427255, ECO:0000269|PubMed:9792858}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa (RP) [MIM:268000]: 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. {ECO:0000269|PubMed:11139241, ECO:0000269|PubMed:9427255, ECO:0000269|PubMed:9792858}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.338

Intolerance Scores

loftool: 0.114
rvis_EVS: 0.08
rvis_percentile_EVS: 60.31

Haploinsufficiency Scores

pHI: 0.785
hipred: Y
hipred_score: 0.592
ghis: 0.460

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.775

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Crx
Phenotype: pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: otx5
Affected structure: pineal complex
Phenotype tag: abnormal
Phenotype quality: process quality

Gene ontology

Biological process: regulation of transcription, DNA-templated;visual perception;circadian rhythm;animal organ morphogenesis;positive regulation of transcription by RNA polymerase II;positive regulation of photoreceptor cell differentiation;response to stimulus
Cellular component: nucleus
Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;nuclear hormone receptor binding;leucine zipper domain binding