Age related macular degeneration 6

Summary

Age related macular degeneration 6 (MONDO:0013406) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 69

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	age related macular degeneration 6
Mondo ID	MONDO:0013406
MeSH	C563674
OMIM	613757
DOID	DOID:0110018
UMLS	C3151060
MedGen	462410
GARD	0024919
Is cancer (heuristic)	no

Also known as: age related macular degeneration type 6 · age-related macular degeneration caused by mutation in RAX2 · ARMD6 · macular degeneration, age-related, 6 · macular Degeneration, age-related, type 6 · RAX2 age-related macular degeneration

Data availability: 69 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › degeneration of macula and posterior pole › age-related macular degeneration › age related macular degeneration 6

Related subtypes (14): wet macular degeneration, age related macular degeneration 2, age related macular degeneration 1, macular degeneration, age-related, 3, age related macular degeneration 7, age related macular degeneration 4, age related macular degeneration 9, age related macular degeneration 10, age related macular degeneration 11, age related macular degeneration 8, age related macular degeneration 12, age related macular degeneration 14, macular dystrophy with central cone involvement, dry age related macular degeneration

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

69 retrieved; paginated sample, class counts are floors:

36 uncertain significance, 14 benign, 10 benign/likely benign, 9 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
262101	NM_001319074.4(RAX2):c.432G>A (p.Ala144=)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
328967	NM_001319074.4(RAX2):c.217-8C>A	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
328969	NM_001319074.4(RAX2):c.156G>A (p.Pro52=)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
328971	NM_001319074.4(RAX2):c.76A>C (p.Lys26Gln)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
328972	NM_001319074.4(RAX2):c.19G>A (p.Glu7Lys)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
834258	NM_001319074.4(RAX2):c.236G>A (p.Arg79Gln)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889123	NM_001319074.4(RAX2):c.385G>A (p.Val129Met)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889200	NM_001319074.4(RAX2):c.49G>C (p.Gly17Arg)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
892560	NM_001319074.4(RAX2):c.131G>A (p.Arg44Gln)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1240	NM_001319074.4(RAX2):c.260G>A (p.Arg87Gln)	RAX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
328940	NM_001319074.4(RAX2):c.*1523T>C	RAX2	Uncertain significance	criteria provided, single submitter
328941	NM_001319074.4(RAX2):c.*1483C>T	RAX2	Uncertain significance	criteria provided, single submitter
328949	NM_001319074.4(RAX2):c.*972T>A	RAX2	Uncertain significance	criteria provided, single submitter
328950	NM_001319074.4(RAX2):c.*949C>T	RAX2	Uncertain significance	criteria provided, single submitter
328959	NM_001319074.4(RAX2):c.*624G>A	RAX2	Uncertain significance	criteria provided, single submitter
328963	NM_001319074.4(RAX2):c.*88C>T	RAX2	Uncertain significance	criteria provided, single submitter
328965	NM_001319074.4(RAX2):c.*7C>T	RAX2	Uncertain significance	criteria provided, single submitter
328970	NM_001319074.4(RAX2):c.83G>A (p.Arg28Gln)	RAX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
328973	NM_001319074.4(RAX2):c.-269+8C>T	RAX2	Uncertain significance	criteria provided, single submitter
328976	NM_001319074.4(RAX2):c.-286G>T	RAX2	Uncertain significance	criteria provided, single submitter
328978	NM_001319074.4(RAX2):c.-319C>A	RAX2	Uncertain significance	criteria provided, single submitter
3892258	NM_001319074.4(RAX2):c.537G>C (p.Arg179Ser)	RAX2	Uncertain significance	criteria provided, single submitter
888997	NM_001319074.4(RAX2):c.*918G>A	RAX2	Uncertain significance	criteria provided, single submitter
888998	NM_001319074.4(RAX2):c.*897C>T	RAX2	Uncertain significance	criteria provided, single submitter
889062	NM_001319074.4(RAX2):c.*552C>T	RAX2	Uncertain significance	criteria provided, single submitter
889063	NM_001319074.4(RAX2):c.*501C>T	RAX2	Uncertain significance	criteria provided, single submitter
889122	NM_001319074.4(RAX2):c.413C>T (p.Pro138Leu)	RAX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
889124	NM_001319074.4(RAX2):c.320C>T (p.Pro107Leu)	RAX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
889690	NM_001319074.4(RAX2):c.*784C>T	RAX2	Uncertain significance	criteria provided, single submitter
889691	NM_001319074.4(RAX2):c.*776C>T	RAX2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAX2	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
RAX2	HGNC:18286	ENSG00000173976	Q96IS3	Retina and anterior neural fold homeobox protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAX2	Retina and anterior neural fold homeobox protein 2	May be involved in modulating the expression of photoreceptor specific genes.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RAX2	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_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
buccal mucosa cell	1
tendon of biceps brachii	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAX2	39	tissue_specific	marker	tendon of biceps brachii, buccal mucosa cell, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAX2	754

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RAX2	Q96IS3	71.72

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
visual perception	1	79.5×	0.038	RAX2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.086	RAX2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	RAX2

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
RAX2	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	RAX2

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)
RAX2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.