Cone-rod dystrophy 21

disease

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Also known as cone-rod dystrophy caused by mutation in DRAM2cone-rod dystrophy type 21CORD21DRAM2 cone-rod dystrophy

Summary

Cone-rod dystrophy 21 (MONDO:0014669) is a disease caused by DRAM2 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: DRAM2 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 21
Mondo ID	MONDO:0014669
OMIM	616502
DOID	DOID:0081447
UMLS	C4049066
MedGen	891534
GARD	0016125
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy 21 · cone-rod dystrophy caused by mutation in DRAM2 · cone-rod dystrophy type 21 · CORD21 · DRAM2 cone-rod dystrophy

Data availability: 15 ClinVar variants · 3 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 21

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

15 retrieved; paginated sample, class counts are floors:

6 pathogenic, 3 likely pathogenic, 3 uncertain significance, 2 benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1322768	NM_001349884.2(DRAM2):c.80dup (p.Tyr27Ter)	DRAM2	Pathogenic	criteria provided, multiple submitters, no conflicts
192233	NM_001349884.2(DRAM2):c.140del (p.Gly47fs)	DRAM2	Pathogenic	criteria provided, single submitter
192234	NM_001349884.2(DRAM2):c.61GCT[1] (p.Ala22del)	DRAM2	Pathogenic	criteria provided, single submitter
192237	NM_001349884.2(DRAM2):c.362A>T (p.His121Leu)	DRAM2	Pathogenic	criteria provided, single submitter
192238	NM_001349884.2(DRAM2):c.131G>A (p.Ser44Asn)	DRAM2	Pathogenic	criteria provided, single submitter
192239	NM_001349884.2(DRAM2):c.494G>A (p.Trp165Ter)	DRAM2	Pathogenic	criteria provided, multiple submitters, no conflicts
1299331	NM_001349884.2(DRAM2):c.98_99del (p.Leu33fs)	DRAM2	Likely pathogenic	criteria provided, single submitter
2093364	NM_001349884.2(DRAM2):c.601-1G>A	DRAM2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
369954	NM_001349884.2(DRAM2):c.568G>T (p.Glu190Ter)	DRAM2	Likely pathogenic	no assertion criteria provided
863836	NM_001349884.2(DRAM2):c.737T>C (p.Leu246Pro)	DRAM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1382952	NM_001349884.2(DRAM2):c.134A>G (p.Asp45Gly)	DRAM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1521035	NM_001349884.2(DRAM2):c.199+6T>G	DRAM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
943340	NM_001349884.2(DRAM2):c.5GGT[1] (p.Trp3del)	DRAM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
677168	NM_001349884.2(DRAM2):c.601-9A>G	DRAM2	Benign	criteria provided, multiple submitters, no conflicts
677169	NM_001349884.2(DRAM2):c.693+14A>G	DRAM2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
DRAM2	Strong	Autosomal recessive	cone-rod dystrophy 21	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DRAM2	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
DRAM2	HGNC:28769	ENSG00000156171	Q6UX65	DNA damage-regulated autophagy modulator protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DRAM2	DNA damage-regulated autophagy modulator protein 2	Plays a role in the initiation of autophagy.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DRAM2	Other/Unknown	no		CWH43_N, DRAM/TMEM150_Autophagy_Mod

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
leukocyte	1
monocyte	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DRAM2	260	ubiquitous	marker	monocyte, leukocyte, spleen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DRAM2	556

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DRAM2	Q6UX65	91.35

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
photoreceptor cell maintenance	1	358.6×	0.010	DRAM2
retina development in camera-type eye	1	255.3×	0.010	DRAM2
regulation of autophagy	1	240.7×	0.010	DRAM2
autophagy	1	110.1×	0.014	DRAM2
cell population proliferation	1	102.8×	0.014	DRAM2
visual perception	1	79.5×	0.015	DRAM2
apoptotic process	1	28.7×	0.035	DRAM2

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
DRAM2	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	DRAM2

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)
DRAM2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: DRAM2