Cone-rod dystrophy 20

Summary

Cone-rod dystrophy 20 (MONDO:0014427) is a disease caused by POC1B (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: POC1B (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 82

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 20
Mondo ID	MONDO:0014427
OMIM	615973
DOID	DOID:0111026
UMLS	C4014856
MedGen	863293
GARD	0016036
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy 20 · cone-rod dystrophy caused by mutation in POC1B · cone-rod dystrophy type 20 · CORD20 · POC1B cone-rod dystrophy

Data availability: 82 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 › cone-rod dystrophy › cone-rod dystrophy 20

Related subtypes (27): cone-rod dystrophy 2, macular degeneration, X-linked atrophic, cone-rod dystrophy 1, cone-rod dystrophy 5, cone-rod dystrophy 6, cone dystrophy 3, cone-rod dystrophy 7, cone-rod dystrophy 3, Leber congenital amaurosis 4, cone-rod dystrophy 8, Newfoundland cone-rod dystrophy, cone-rod dystrophy 13, cone-rod dystrophy 10, cone-rod dystrophy 11, retinal cone dystrophy 4, cone-rod dystrophy 12, cone-rod dystrophy 9, cone-rod dystrophy 15, cone-rod dystrophy 16, cone-rod dystrophy 17, cone-rod dystrophy 18, cone-rod dystrophy 19, cone-rod dystrophy 21, X-linked cone-rod dystrophy, cone-rod dystrophy 22, cone-rod dystrophy 14, cone-rod dystrophy 24

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

82 retrieved; paginated sample, class counts are floors:

58 uncertain significance, 9 conflicting classifications of pathogenicity, 5 pathogenic, 5 likely pathogenic, 3 pathogenic/likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029264	NM_172240.3(POC1B):c.144del (p.Lys48fs)	POC1B	Pathogenic	criteria provided, multiple submitters, no conflicts
1323482	NM_172240.3(POC1B):c.417del (p.Leu140fs)	POC1B	Pathogenic	criteria provided, single submitter
155769	NM_172240.3(POC1B):c.317G>C (p.Arg106Pro)	POC1B	Pathogenic	criteria provided, multiple submitters, no conflicts
155770	NM_172240.3(POC1B):c.199_201del (p.Gln67del)	POC1B	Pathogenic	no assertion criteria provided
155771	NM_172240.3(POC1B):c.810+1G>T	POC1B	Pathogenic	criteria provided, multiple submitters, no conflicts
859104	NM_172240.3(POC1B):c.676+1G>A	POC1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
859795	NM_172240.3(POC1B):c.101-3T>G	POC1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
987339	NM_172240.3(POC1B):c.1332_1333dup (p.Thr445fs)	POC1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
992468	NM_172240.3(POC1B):c.52A>T (p.Lys18Ter)	LOC130008356	Likely pathogenic	criteria provided, single submitter
1066266	NM_172240.3(POC1B):c.453-7_453-2del	POC1B	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3575510	NM_172240.3(POC1B):c.1054del (p.Ile352fs)	POC1B	Likely pathogenic	criteria provided, single submitter
3575511	NM_172240.3(POC1B):c.1032+1G>A	POC1B	Likely pathogenic	criteria provided, single submitter
3575517	NM_172240.3(POC1B):c.750dup (p.Thr251fs)	POC1B	Likely pathogenic	criteria provided, single submitter
1078187	NM_172240.3(POC1B):c.132A>T (p.Leu44=)	POC1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1106634	NM_172240.3(POC1B):c.1259G>C (p.Ser420Thr)	POC1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1121607	NM_172240.3(POC1B):c.250G>A (p.Val84Met)	POC1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1172722	NM_172240.3(POC1B):c.1332+5G>A	POC1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1639201	NM_172240.3(POC1B):c.1113+13_1113+14insG	POC1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3575508	NM_172240.3(POC1B):c.1185C>T (p.Ser395=)	POC1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3775701	NM_172240.3(POC1B):c.1354C>T (p.Arg452Ter)	POC1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
961472	NM_172240.3(POC1B):c.923G>A (p.Gly308Asp)	POC1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
964371	NM_172240.3(POC1B):c.424C>T (p.Arg142Ter)	POC1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1519783	NM_172240.3(POC1B):c.88G>A (p.Gly30Ser)	LOC130008356	Uncertain significance	criteria provided, multiple submitters, no conflicts
1949676	NM_172240.3(POC1B):c.46G>A (p.Gly16Ser)	LOC130008356	Uncertain significance	criteria provided, multiple submitters, no conflicts
3575531	NM_172240.3(POC1B):c.76C>G (p.Leu26Val)	LOC130008356	Uncertain significance	criteria provided, single submitter
3575532	NM_172240.3(POC1B):c.47G>T (p.Gly16Val)	LOC130008356	Uncertain significance	criteria provided, single submitter
3575533	NM_172240.3(POC1B):c.15+5G>C	LOC130008357	Uncertain significance	criteria provided, single submitter
3575534	NM_172240.3(POC1B):c.8C>T (p.Ser3Leu)	LOC130008357	Uncertain significance	criteria provided, single submitter
855489	NM_172240.3(POC1B):c.10G>A (p.Ala4Thr)	LOC130008357	Uncertain significance	criteria provided, multiple submitters, no conflicts
1009822	NM_172240.3(POC1B):c.1239G>A (p.Met413Ile)	POC1B	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
POC1B	Definitive	Autosomal recessive	cone-rod dystrophy 20	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POC1B	Orphanet:1872	Cone rod dystrophy

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
POC1B	HGNC:30836	ENSG00000139323	Q8TC44	POC1 centriolar protein homolog B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POC1B	POC1 centriolar protein homolog B	Plays an important role in centriole assembly and/or stability and ciliogenesis.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POC1B	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS

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
corpus callosum	1
epithelial cell of pancreas	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POC1B	248	ubiquitous	marker	epithelial cell of pancreas, sperm, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POC1B	2,545

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
POC1B	Q8TC44	77.62

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
positive regulation of centriole elongation	1	2407.4×	0.003	POC1B
retina homeostasis	1	1123.5×	0.003	POC1B
centriole replication	1	732.7×	0.003	POC1B
homeostasis of number of cells	1	674.1×	0.003	POC1B
sperm flagellum assembly	1	674.1×	0.003	POC1B
acrosome assembly	1	455.5×	0.004	POC1B
single fertilization	1	183.2×	0.008	POC1B
cell morphogenesis	1	157.5×	0.008	POC1B
cell population proliferation	1	102.8×	0.011	POC1B
cilium assembly	1	73.6×	0.014	POC1B

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
POC1B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	POC1B

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
POC1B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.