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

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;Cone-rod dystrophy 2 (17 variants)
• Cone-rod dystrophy 2;Leber congenital amaurosis 7 (17 variants)
• not provided (10 variants)
• Cone-rod dystrophy 2 (5 variants)
• Retinal dystrophy (5 variants)
• Leber congenital amaurosis 7 (4 variants)
• Retinitis pigmentosa (2 variants)
• Benign concentric annular macular dystrophy (2 variants)
• Cone-rod dystrophy (2 variants)
• Leber congenital amaurosis 1 (1 variants)
• See cases (1 variants)
• Leber congenital amaurosis (1 variants)
• Stargardt disease (1 variants)
• maculopathy (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	68	4	77
missense	7	5	122	8	1	143
nonsense	7	6	4			17
start loss						0
frameshift	25	14	25			64
inframe indel	1					1
splice donor/acceptor (+/-2bp)	2	2	1			5
splice region		1	3	4		8
non coding			50	24	42	116
Total	42	27	207	100	47

Highest pathogenic variant AF is 0.0000197

Variants in CRX

This is a list of pathogenic ClinVar variants found in the CRX region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-47821930-T-C		Cone-Rod Dystrophy, Dominant • Leber congenital amaurosis • Retinitis Pigmentosa, Dominant	Benign (Jun 14, 2016)
19-47821991-C-T		Leber congenital amaurosis 7 • Cone-rod dystrophy 2 • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
19-47822000-C-T		Leber congenital amaurosis 7 • Retinitis pigmentosa • Cone-rod dystrophy 2	Uncertain significance (Jan 12, 2018)
19-47822007-G-C		Cone-rod dystrophy 2 • Leber congenital amaurosis 7 • Retinitis pigmentosa	Benign/Likely benign (Jan 13, 2018)
19-47834259-T-C			Benign (Jun 18, 2021)
19-47834289-A-G			Benign (Nov 10, 2018)
19-47834415-T-A			Likely benign (May 29, 2018)
19-47834451-C-T		Leber congenital amaurosis 7;Cone-rod dystrophy 2 • Retinal dystrophy • CRX-related disorder	Uncertain significance (Dec 18, 2023)
19-47834452-G-A		Leber congenital amaurosis 7;Cone-rod dystrophy 2	Likely benign (Aug 30, 2023)
19-47834454-A-G		Cone-rod dystrophy 2;Leber congenital amaurosis 7	Uncertain significance (Aug 10, 2023)
19-47834463-C-T		Cone-rod dystrophy 2;Leber congenital amaurosis 7	Uncertain significance (Nov 20, 2023)
19-47834463-C-CG		Retinal dystrophy	Likely pathogenic (Jun 28, 2019)
19-47834464-G-A		Leber congenital amaurosis 7;Cone-rod dystrophy 2	Likely benign (Jul 07, 2023)
19-47834465-G-C		Cone-rod dystrophy 2;Leber congenital amaurosis 7	Likely benign (Jul 24, 2023)
19-47834468-C-T		Leber congenital amaurosis 7;Cone-rod dystrophy 2	Uncertain significance (Aug 04, 2021)
19-47834471-C-G		Cone-rod dystrophy 2 • Leber congenital amaurosis 7 • Retinitis pigmentosa • Leber congenital amaurosis 7;Cone-rod dystrophy 2	Conflicting classifications of pathogenicity (Jan 25, 2024)
19-47834472-A-G		Usher syndrome	Uncertain significance (Jun 05, 2020)
19-47834480-G-C		Cone-rod dystrophy 2;Leber congenital amaurosis 7	Uncertain significance (Jun 23, 2023)
19-47834485-C-A		Leber congenital amaurosis 7;Cone-rod dystrophy 2	Uncertain significance (Nov 19, 2021)
19-47834485-C-T		Leber congenital amaurosis 7;Cone-rod dystrophy 2	Likely benign (Jan 14, 2023)
19-47834486-G-A		Leber congenital amaurosis 7;Cone-rod dystrophy 2	Uncertain significance (Jul 10, 2023)
19-47834486-G-C		Retinal dystrophy • Leber congenital amaurosis 7;Cone-rod dystrophy 2	Uncertain significance (Oct 03, 2022)
19-47834495-C-T		Cone-rod dystrophy 2;Leber congenital amaurosis 7	Likely benign (Jul 03, 2023)
19-47834503-C-G		Cone-rod dystrophy 2;Leber congenital amaurosis 7	Uncertain significance (Oct 28, 2022)
19-47834503-C-T		Leber congenital amaurosis 7;Cone-rod dystrophy 2	Likely benign (Oct 17, 2022)

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