CERKL

Chr 2AR

CERK like autophagy regulator

Also known as: RP26

NCBI Gene: 375298 ENSG00000188452 UniProt: Q49MI3 OMIM: 608381

This gene was initially identified as a locus (RP26) associated with an autosomal recessive form of retinitis pigmentosa (arRP) disease. This gene encodes a protein with ceramide kinase-like domains, however, the protein does not phosphorylate ceramide and its target substrate is currently unknown. This protein may be a negative regulator of apoptosis in photoreceptor cells. Mutations in this gene cause a form of retinitis pigmentosa characterized by autosomal recessive cone and rod dystrophy (arCRD). Alternative splicing of this gene results in multiple transcript variants encoding different isoforms and non-coding transcripts.[provided by RefSeq, May 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.541 OMIM phenotype

Clinical Summary— CERKL

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Gene-Disease Validity (ClinGen)

CERKL-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

213 unique Pathogenic / Likely Pathogenic· 323 VUS of 1089 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.54LOEUF

pLI 0.000

Z-score -0.80

OE 1.16 (0.88–1.54)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.27Z-score

OE missense 1.04 (0.95–1.15)

316 obs / 303.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.16 (0.88–1.54)

0≤0.351.4

Missense OE?1.04 (0.95–1.15)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 34 / 29.3Missense obs/exp: 316 / 303.0Syn Z: 0.17

ClinVar Variant Classifications

1089 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic79

Likely Pathogenic134

VUS323

Likely Benign459

Benign37

Conflicting50

Pathogenic

134

Likely Pathogenic

323

VUS

459

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	68	4	7	0	79
Likely Pathogenic	115	12	7	0	134
VUS	11	239	63	10	323
Likely Benign	1	7	201	250	459
Benign	0	3	30	4	37
Conflicting	—				50
Total	195	265	308	264	1,082

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

29 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap CERKL — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →