CERKL

ceramide kinase like

Basic information

Region (hg38): 2:181535040-181680665

Previous symbols: [ "RP26" ]

Links

ENSG00000188452 ∙ NCBI:375298 ∙ OMIM:608381 ∙ HGNC:21699 ∙ Uniprot:Q49MI3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 26 (Definitive), mode of inheritance: AR
• retinitis pigmentosa 26 (Strong), mode of inheritance: AR
• CERKL-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 26	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	14681825

ClinVar

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

• not provided (857 variants)
• Retinitis pigmentosa 26 (167 variants)
• Retinitis pigmentosa (101 variants)
• Maturity-onset diabetes of the young type 6 (50 variants)
• Inborn genetic diseases (38 variants)
• not specified (25 variants)
• Retinal dystrophy (23 variants)
• Maturity-onset diabetes of the young type 6;Type 2 diabetes mellitus (14 variants)
• Type 2 diabetes mellitus;Maturity-onset diabetes of the young type 6 (14 variants)
• Maturity onset diabetes mellitus in young (9 variants)
• Retinitis Pigmentosa, Recessive (7 variants)
• Autosomal recessive retinitis pigmentosa (4 variants)
• Cone-rod dystrophy (4 variants)
• Monogenic diabetes (2 variants)
• NEUROD1-related condition (2 variants)
• Retinal pigment epithelial atrophy;Cone dystrophy (2 variants)
• Hypoinsulinemia (1 variants)
• Isolated macular dystrophy (1 variants)
• See cases (1 variants)
• Severe photosensitivity;Macular dystrophy;Adult-onset night blindness (1 variants)
• Stargardt disease (1 variants)
• CERKL-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CERKL 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			3	190	4	197
missense	1	5	179	2	3	190
nonsense	23	14	2			39
start loss	4					4
frameshift	34	22	6			62
inframe indel			5			5
splice donor/acceptor (+/-2bp)	4	29	1			34
splice region		3	14	46	2	65
non coding		3	186	143	31	363
Total	66	73	382	335	38

Highest pathogenic variant AF is 0.0000723

Variants in CERKL

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

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

Position	Type	Phenotype	Significance	ClinVar
2-181535420-T-TGCTATTTTC		ITGA4-related disorder	Likely benign (Dec 07, 2020)
2-181535451-A-G		not specified	Uncertain significance (Sep 17, 2021)
2-181536661-C-T		Retinitis Pigmentosa, Recessive	Likely benign (Jun 14, 2016)
2-181536766-A-ACAAT		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
2-181536813-G-A		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
2-181536839-C-T		Retinitis pigmentosa	Benign (Jan 13, 2018)
2-181536860-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
2-181536968-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
2-181536972-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
2-181536977-G-C		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
2-181537025-G-A		Retinitis pigmentosa	Benign (Jan 13, 2018)
2-181537126-A-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
2-181537139-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
2-181537140-G-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
2-181537161-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
2-181537205-G-A		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
2-181537230-G-T		Retinitis pigmentosa	Benign (Jan 13, 2018)
2-181537269-G-C		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
2-181537304-C-T		Retinitis pigmentosa	Benign (Jan 13, 2018)
2-181537315-G-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
2-181537404-A-G		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
2-181537441-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
2-181537489-C-CT		Retinitis Pigmentosa, Recessive	Likely benign (Jun 14, 2016)
2-181537611-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
2-181537617-A-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CERKL	protein_coding	protein_coding	ENST00000339098	14	143990

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.84e-25	0.0000676	125553	0	195	125748	0.000776

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.266	316	303	1.04	0.0000148	3626
Missense in Polyphen		83	92.682	0.89553		1137
Synonymous	0.173	107	109	0.979	0.00000549	1061
Loss of Function	-0.797	34	29.3	1.16	0.00000147	352

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00113	0.00113
Ashkenazi Jewish	0.00	0.00
East Asian	0.000550	0.000544
Finnish	0.00132	0.00129
European (Non-Finnish)	0.000888	0.000862
Middle Eastern	0.000550	0.000544
South Asian	0.000794	0.000784
Other	0.000494	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has no detectable ceramide-kinase activity. Overexpression of CERKL protects cells from apoptosis in oxidative stress conditions. {ECO:0000269|PubMed:15708351, ECO:0000269|PubMed:19158957}.
• Disease: DISEASE: Retinitis pigmentosa 26 (RP26) [MIM:608380]: 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:14681825, ECO:0000269|PubMed:18978954}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0976

Intolerance Scores

• loftool: 0.988
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.73

Haploinsufficiency Scores

• pHI: 0.345
• hipred: N
• hipred_score: 0.264
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.224

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cerkl
• Phenotype: cellular phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: cerkl
• Affected structure: retinal rod cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: phosphorylation;sphingolipid biosynthetic process
• Cellular component: photoreceptor outer segment;photoreceptor inner segment;nucleus;nucleolus;endoplasmic reticulum;Golgi apparatus;cytosol;perinuclear region of cytoplasm
• Molecular function: NAD+ kinase activity;sphingolipid binding