Retinitis pigmentosa 67

Summary

Retinitis pigmentosa 67 (MONDO:0014256) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 67
Mondo ID	MONDO:0014256
OMIM	615565
DOID	DOID:0110359
UMLS	C3809954
MedGen	816284
GARD	0015988
Is cancer (heuristic)	no

Also known as: NEK2 retinitis pigmentosa · retinitis pigmentosa 67 · retinitis pigmentosa caused by mutation in NEK2 · retinitis pigmentosa type 67 · RP67

Data availability: 6 ClinVar variants · 4 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 67

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 26, 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 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

6 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 conflicting classifications of pathogenicity, 1 benign, 1 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
91391	NM_002497.4(NEK2):c.617_624delinsA (p.Leu206fs)	NEK2	Pathogenic	no assertion criteria provided
1961655	NM_002497.4(NEK2):c.803del (p.Asn268fs)	NEK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032832	NM_002497.4(NEK2):c.97-2A>G	NEK2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1420570	NM_002497.4(NEK2):c.725A>C (p.Asp242Ala)	NEK2	Uncertain significance	criteria provided, multiple submitters, no conflicts
403228	NM_002497.4(NEK2):c.504T>C (p.His168=)	NEK2	Benign	criteria provided, multiple submitters, no conflicts
709034	NM_002497.4(NEK2):c.863G>A (p.Arg288Gln)	NEK2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
NEK2	Moderate	Autosomal recessive	retinitis pigmentosa 67	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NEK2	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NEK2	HGNC:7745	ENSG00000117650	P51955	Serine/threonine-protein kinase Nek2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NEK2	Serine/threonine-protein kinase Nek2	Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells.

Protein-family classification

Druggable: 1 · 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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NEK2	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ cell	1
sperm	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NEK2	206	ubiquitous	marker	sperm, ventricular zone, male germ cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NEK2	3,608

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NEK2	P51955	30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 1 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
APC-Cdc20 mediated degradation of Nek2A	1	423.0×	0.012	NEK2
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1	423.0×	0.012	NEK2
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1	407.9×	0.012	NEK2
APC/C:Cdc20 mediated degradation of mitotic proteins	1	356.9×	0.012	NEK2
APC/C-mediated degradation of cell cycle proteins	1	335.9×	0.012	NEK2
Regulation of mitotic cell cycle	1	335.9×	0.012	NEK2
Centrosome maturation	1	253.8×	0.012	NEK2
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	1	237.9×	0.012	NEK2
Loss of Nlp from mitotic centrosomes	1	158.6×	0.012	NEK2
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.012	NEK2
AURKA Activation by TPX2	1	152.3×	0.012	NEK2
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.012	NEK2
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.012	NEK2
Mitotic G2-G2/M phases	1	126.9×	0.012	NEK2
G2/M Transition	1	126.9×	0.012	NEK2
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.012	NEK2
Anchoring of the basal body to the plasma membrane	1	113.1×	0.012	NEK2
Cilium Assembly	1	108.8×	0.012	NEK2
Mitotic Prometaphase	1	69.2×	0.017	NEK2
Organelle biogenesis and maintenance	1	66.0×	0.017	NEK2
M Phase	1	66.0×	0.017	NEK2
Cell Cycle, Mitotic	1	48.2×	0.023	NEK2
Dengue Virus-Host Interactions	1	45.7×	0.023	NEK2
Cell Cycle	1	36.0×	0.028	NEK2

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of centriole-centriole cohesion	1	16852.0×	8e-04	NEK2
centrosome separation	1	5617.3×	0.001	NEK2
regulation of mitotic centrosome separation	1	3370.4×	0.001	NEK2
regulation of attachment of spindle microtubules to kinetochore	1	1685.2×	0.002	NEK2
blastocyst development	1	674.1×	0.003	NEK2
regulation of mitotic nuclear division	1	624.1×	0.003	NEK2
positive regulation of telomere maintenance	1	510.7×	0.004	NEK2
spindle assembly	1	443.5×	0.004	NEK2
mitotic spindle assembly	1	343.9×	0.004	NEK2
meiotic cell cycle	1	244.2×	0.005	NEK2
chromosome segregation	1	173.7×	0.007	NEK2
mitotic cell cycle	1	133.8×	0.008	NEK2
cell division	1	46.2×	0.022	NEK2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
NEK2	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NEK2	23	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	NEK2
FEDRATINIB	4	NEK2
NERATINIB	4	NEK2
PALBOCICLIB	4	NEK2
BOSUTINIB	4	NEK2
GILTERITINIB	4	NEK2
PAZOPANIB	4	NEK2
SUNITINIB	4	NEK2
DASATINIB	4	NEK2
DACTOLISIB	3	NEK2
QUERCETIN	3	NEK2
DOVITINIB	3	NEK2
LESTAURTINIB	3	NEK2
SU-014813	2	NEK2
CENISERTIB	2	NEK2
ADAVOSERTIB	2	NEK2
ILORASERTIB	2	NEK2
R-406	2	NEK2
BI-2536	2	NEK2
PELITINIB	2	NEK2
GSK-461364	1	NEK2
KW-2449	1	NEK2
CYC-116	1	NEK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
NEK2	471	Binding:469, Functional:1, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NEK2	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
NEK2	471

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

23 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.

Compound	Max phase	Cohort target (bioactivity)
VEMURAFENIB	4	NEK2
FEDRATINIB	4	NEK2
NERATINIB	4	NEK2
PALBOCICLIB	4	NEK2
BOSUTINIB	4	NEK2
GILTERITINIB	4	NEK2
PAZOPANIB	4	NEK2
SUNITINIB	4	NEK2
DASATINIB	4	NEK2
DACTOLISIB	3	NEK2
QUERCETIN	3	NEK2
DOVITINIB	3	NEK2
LESTAURTINIB	3	NEK2
SU-014813	2	NEK2
CENISERTIB	2	NEK2
ADAVOSERTIB	2	NEK2
ILORASERTIB	2	NEK2
R-406	2	NEK2
BI-2536	2	NEK2
PELITINIB	2	NEK2
GSK-461364	1	NEK2
KW-2449	1	NEK2
CYC-116	1	NEK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	NEK2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.