Retinitis pigmentosa 26

Summary

Retinitis pigmentosa 26 (MONDO:0012024) is a disease caused by CERKL (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CERKL (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 279

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 26
Mondo ID	MONDO:0012024
MeSH	C564249
OMIM	608380
DOID	DOID:0110368
UMLS	C1842127
MedGen	333996
GARD	0010397
Is cancer (heuristic)	no

Also known as: CERKL retinitis pigmentosa · retinitis pigmentosa 26 · retinitis pigmentosa caused by mutation in CERKL · retinitis pigmentosa type 26 · RP 26 · RP26

Data availability: 279 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › retinitis pigmentosa › retinitis pigmentosa 26

Related subtypes (101): retinitis pigmentosa 6, cone-rod dystrophy 2, retinitis pigmentosa 1, retinitis pigmentosa 9, retinitis pigmentosa 10, dominant pericentral pigmentary retinopathy, late-adult onset retinitis pigmentosa, autosomal recessive pericentral pigmentary retinopathy, retinitis pigmentosa 3, retinitis pigmentosa 24, retinitis pigmentosa 23, retinitis pigmentosa 34, retinitis pigmentosa 2, retinitis pigmentosa Y-linked, retinitis pigmentosa 13, retinitis pigmentosa 12, retinitis pigmentosa 14, retinitis pigmentosa 11, retinitis pigmentosa 17, retinitis pigmentosa 18, retinitis pigmentosa 19, retinitis pigmentosa 22, retinitis pigmentosa 25, retinitis pigmentosa 28, retinitis pigmentosa 30, retinitis pigmentosa 7, retinitis pigmentosa 32, retinitis pigmentosa 31, retinitis pigmentosa 35, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 37, retinitis pigmentosa 41, retinitis pigmentosa 29, retinitis pigmentosa 46, retinitis pigmentosa 42, retinitis pigmentosa 50, retinitis pigmentosa 54, retinitis pigmentosa 51, retinitis pigmentosa 55, retinitis pigmentosa 56, retinitis pigmentosa 57, retinitis pigmentosa 58, cone-rod dystrophy 15, retinitis pigmentosa 4, retinitis pigmentosa 27, retinitis pigmentosa 49, retinitis pigmentosa 47, retinitis pigmentosa 45, retinitis pigmentosa 44, retinitis pigmentosa 20, retinitis pigmentosa 40, retinitis pigmentosa 39, retinitis pigmentosa 43, retinitis pigmentosa 48, retinitis pigmentosa 59, retinitis pigmentosa 38, retinitis pigmentosa 60, retinitis pigmentosa 61, retinitis pigmentosa 62, retinitis pigmentosa 63, cone-rod dystrophy 16, retinitis pigmentosa 66, retinitis pigmentosa with or without situs inversus, retinitis pigmentosa 67, retinitis pigmentosa 68, retinitis pigmentosa 69, retinitis pigmentosa 70, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, retinitis pigmentosa 74, retinitis pigmentosa 75, retinitis pigmentosa 76, retinitis pigmentosa 77, retinitis pigmentosa 92, retinitis pigmentosa 93, retinitis pigmentosa 83, retinitis pigmentosa 84, retinitis pigmentosa 85, retinitis pigmentosa 86, retinitis pigmentosa 87 with choroidal involvement, retinitis pigmentosa 88, retinitis pigmentosa 90, retinitis pigmentosa 81, retinitis pigmentosa 78, retinitis pigmentosa 79, retinitis pigmentosa 80, retinitis pigmentosa 94, variable age at onset, retinitis pigmentosa 53, retinitis pigmentosa 65, retinitis pigmentosa 64, retinitis pigmentosa 95, retinitis pigmentosa 96, retinitis pigmentosa 97, retinitis pigmentosa 98, retinitis pigmentosa 99, retinitis pigmentosa 100, retinitis pigmentosa 101, retinitis pigmentosa 7, digenic

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

279 retrieved; paginated sample, class counts are floors:

87 uncertain significance, 64 likely pathogenic, 44 pathogenic/likely pathogenic, 32 conflicting classifications of pathogenicity, 21 pathogenic, 16 likely benign, 14 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
424768	NM_201548.4(CERKL):c.[674A>T];[769C>T]		Pathogenic	criteria provided, single submitter
1065700	NM_201548.5(CERKL):c.109C>T (p.Gln37Ter)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065714	NM_201548.5(CERKL):c.366_367del (p.Phe123fs)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066420	NM_201548.5(CERKL):c.820+2C>G	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068911	NM_201548.5(CERKL):c.758del (p.Met253fs)	CERKL	Pathogenic	criteria provided, multiple submitters, no conflicts
1068912	NM_201548.5(CERKL):c.156_157insT (p.Glu53Ter)	CERKL	Pathogenic	criteria provided, multiple submitters, no conflicts
1069741	NM_201548.5(CERKL):c.526C>T (p.Gln176Ter)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072011	NM_201548.5(CERKL):c.1389_1392del (p.Tyr464fs)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072129	NM_201548.5(CERKL):c.954_961dup (p.Ser321fs)	CERKL	Pathogenic	criteria provided, multiple submitters, no conflicts
1075279	NM_201548.5(CERKL):c.8G>A (p.Trp3Ter)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075776	NM_201548.5(CERKL):c.1389_1392dup (p.Thr465fs)	CERKL	Pathogenic	criteria provided, multiple submitters, no conflicts
1076445	NM_201548.5(CERKL):c.397_401del (p.Leu133fs)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1302082	NM_201548.5(CERKL):c.112C>T (p.Gln38Ter)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1308275	NM_201548.5(CERKL):c.316C>T (p.Arg106Cys)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1425842	NM_201548.5(CERKL):c.848_849del (p.Leu283fs)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1442655	NM_201548.5(CERKL):c.1392C>G (p.Tyr464Ter)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453528	NM_201548.5(CERKL):c.677+562del	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455683	NM_201548.5(CERKL):c.1361dup (p.Asn454fs)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457258	NM_201548.5(CERKL):c.1227C>A (p.Cys409Ter)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1494511	NM_201548.5(CERKL):c.182T>A (p.Val61Glu)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1723321	NM_201548.5(CERKL):c.568del (p.Val190fs)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2017481	NM_201548.5(CERKL):c.271G>T (p.Glu91Ter)	CERKL	Pathogenic	criteria provided, multiple submitters, no conflicts
2071035	NM_201548.5(CERKL):c.678-1G>C	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2085599	NM_201548.5(CERKL):c.294_295del (p.Phe99fs)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2364	NM_201548.5(CERKL):c.769C>T (p.Arg257Ter)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236491	NM_201548.5(CERKL):c.967_968del (p.Met323fs)	CERKL	Pathogenic	criteria provided, multiple submitters, no conflicts
236492	NM_201548.5(CERKL):c.193G>T (p.Glu65Ter)	CERKL	Pathogenic	criteria provided, multiple submitters, no conflicts
2680671	NM_201548.5(CERKL):c.93del (p.Leu32fs)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2793570	NM_201548.5(CERKL):c.426_430del (p.Asn142fs)	CERKL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280382	NM_201548.5(CERKL):c.1012C>T (p.Arg338Ter)	CERKL	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CERKL	Definitive	Autosomal recessive	retinitis pigmentosa 26	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CERKL	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CERKL	HGNC:21699	ENSG00000188452	Q49MI3	Ceramide kinase-like protein	gencc,clinvar
ITGA4	HGNC:6140	ENSG00000115232	P13612	Integrin alpha-4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CERKL	Ceramide kinase-like protein	Has no detectable ceramide-kinase activity.
ITGA4	Integrin alpha-4	Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	14.6×	0.071
Kinase	1	13.9×	0.071

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CERKL	Kinase	yes		Diacylglycerol_kinase_cat_dom, NAD/diacylglycerol_kinase_sf, ATP-NAD_kinase_N
ITGA4	Antibody/Immunoglobulin	yes		Integrin_alpha, FG-GAP, Int_alpha_beta-p

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
islet of Langerhans	1
male germ line stem cell (sensu Vertebrata) in testis	1
olfactory segment of nasal mucosa	1
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CERKL	122	tissue_specific	marker	islet of Langerhans, olfactory segment of nasal mucosa, male germ line stem cell (sensu Vertebrata) in testis
ITGA4	220	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGA4	3,089
CERKL	959

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGA4	P13612	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CERKL	Q49MI3	79.82

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX3 Regulates Immune Response and Cell Migration	1	1903.3×	0.009	ITGA4
Transcriptional regulation by RUNX3	1	271.9×	0.031	ITGA4
Integrin cell surface interactions	1	134.3×	0.033	ITGA4
Potential therapeutics for SARS	1	114.2×	0.033	ITGA4
Cell surface interactions at the vascular wall	1	95.2×	0.033	ITGA4
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.033	ITGA4
Extracellular matrix organization	1	63.1×	0.038	ITGA4
SARS-CoV Infections	1	55.4×	0.038	ITGA4
Hemostasis	1	36.0×	0.052	ITGA4
Viral Infection Pathways	1	30.8×	0.052	ITGA4
Adaptive Immune System	1	29.8×	0.052	ITGA4
Infectious disease	1	24.8×	0.057	ITGA4
RNA Polymerase II Transcription	1	22.5×	0.058	ITGA4
Gene expression (Transcription)	1	17.8×	0.068	ITGA4
Generic Transcription Pathway	1	15.1×	0.075	ITGA4
Disease	1	13.1×	0.077	ITGA4
Immune System	1	13.0×	0.077	ITGA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete negative regulation of protein homodimerization activity	1	8426.0×	0.002	ITGA4
clathrin-dependent extracellular exosome endocytosis	1	8426.0×	0.002	ITGA4
immune response in gut-associated lymphoid tissue	1	4213.0×	0.002	ITGA4
cell-matrix adhesion involved in ameboidal cell migration	1	4213.0×	0.002	ITGA4
diapedesis	1	1685.2×	0.003	ITGA4
negative regulation of vasoconstriction	1	842.6×	0.004	ITGA4
axonogenesis involved in innervation	1	842.6×	0.004	ITGA4
cell-cell adhesion mediated by integrin	1	766.0×	0.004	ITGA4
positive regulation of leukocyte tethering or rolling	1	766.0×	0.004	ITGA4
sphingolipid metabolic process	1	495.6×	0.005	CERKL
leukocyte tethering or rolling	1	421.3×	0.005	ITGA4
positive regulation of vascular endothelial cell proliferation	1	421.3×	0.005	ITGA4
positive regulation of endothelial cell apoptotic process	1	366.4×	0.005	ITGA4
positive regulation of T cell migration	1	366.4×	0.005	ITGA4
receptor clustering	1	312.1×	0.006	ITGA4
heterotypic cell-cell adhesion	1	290.6×	0.006	ITGA4
cellular response to cytokine stimulus	1	271.8×	0.006	ITGA4
neuron projection extension	1	263.3×	0.006	ITGA4
endodermal cell differentiation	1	247.8×	0.006	ITGA4
leukocyte cell-cell adhesion	1	234.1×	0.006	ITGA4
cellular response to amyloid-beta	1	195.9×	0.007	ITGA4
sphingolipid biosynthetic process	1	179.3×	0.007	CERKL
substrate adhesion-dependent cell spreading	1	172.0×	0.007	ITGA4
B cell differentiation	1	109.4×	0.011	ITGA4
cell-matrix adhesion	1	81.8×	0.013	ITGA4
integrin-mediated signaling pathway	1	80.2×	0.013	ITGA4
cell-cell adhesion	1	50.8×	0.020	ITGA4
negative regulation of apoptotic process	1	17.4×	0.057	CERKL

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CERKL	0	0
ITGA4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ITGA4	299	Binding:282, Functional:17

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ITGA4	299

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ITGA4
D	Druggable family + AlphaFold only, no drug	1	CERKL
E	Difficult family or no structure, no drug	0

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ITGA4	299	—
CERKL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.