congenital disorder of glycosylation, type IIr

Summary

congenital disorder of glycosylation, type IIr (MONDO:0026765) is a disease caused by ATP6AP2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ATP6AP2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital disorder of glycosylation, type IIr
Mondo ID	MONDO:0026765
OMIM	301045
DOID	DOID:0051048
UMLS	C5393313
MedGen	1717186
GARD	0025491
Is cancer (heuristic)	no

Also known as: CDG2R · congenital disorder of glycosylation, type IIr, X-linked recessive

Data availability: 9 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › congenital disorder of glycosylation type II › congenital disorder of glycosylation, type IIr

Related subtypes (25): MGAT2-congenital disorder of glycosylation, leukocyte adhesion deficiency type II, SLC35A2-congenital disorder of glycosylation, SLC35A1-congenital disorder of glycosylation, MOGS-congenital disorder of glycosylation, B4GALT1-congenital disorder of glycosylation, COG7-congenital disorder of glycosylation, COG8-congenital disorder of glycosylation, COG1-congenital disorder of glycosylation, COG4-congenital disorder of glycosylation, COG5-congenital disorder of glycosylation, COG6-congenital disorder of glycosylation, TMEM165-congenital disorder of glycosylation, SLC39A8-CDG, CCDC115-CDG, TMEM199-CDG, congenital disorder of glycosylation, type iit, congenital disorder of glycosylation, type 2v, congenital disorder of glycosylation, type IIw, congenital disorder of glycosylation, type IIq, congenital disorder of glycosylation, type IIy, congenital disorder of glycosylation, type IIz, congenital disorder of glycosylation, type IIaa, congenital disorder of glycosylation, type IIbb, congenital disorder of glycosylation, type IIcc

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

9 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
869366	NM_005765.3(ATP6AP2):c.293T>C (p.Leu98Ser)	ATP6AP2	Pathogenic	no assertion criteria provided
204912	NM_005765.3(ATP6AP2):c.490G>A (p.Val164Ile)	ATP6AP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
533691	NM_005765.3(ATP6AP2):c.858G>A (p.Ala286=)	ATP6AP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1493867	NM_005765.3(ATP6AP2):c.122G>A (p.Arg41Gln)	ATP6AP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1698994	NM_005765.3(ATP6AP2):c.1028C>G (p.Thr343Arg)	ATP6AP2	Uncertain significance	criteria provided, single submitter
389602	NM_005765.3(ATP6AP2):c.212G>A (p.Arg71His)	ATP6AP2	Uncertain significance	criteria provided, single submitter
1192374	NM_005765.3(ATP6AP2):c.534+45G>C	ATP6AP2	Benign	criteria provided, multiple submitters, no conflicts
136465	NM_005765.3(ATP6AP2):c.38-5T>C	ATP6AP2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
199113	NM_005765.3(ATP6AP2):c.1050T>C (p.Asp350=)	ATP6AP2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 2 · 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
ATP6AP2	Strong	X-linked	congenital disorder of glycosylation, type IIr	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP6AP2	Orphanet:363654	X-linked parkinsonism-spasticity syndrome
ATP6AP2	Orphanet:93952	X-linked intellectual disability, Hedera type

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
ATP6AP2	HGNC:18305	ENSG00000182220	O75787	Renin receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP6AP2	Renin receptor	Multifunctional protein which functions as a renin, prorenin cellular receptor and is involved in the assembly of the lysosomal proton-transporting V-type ATPase (V-ATPase) and the acidification of the endo-lysosomal system.

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)
ATP6AP2	Other/Unknown	no		Renin_rcpt, Renin_r_C, RENR_N

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
germinal epithelium of ovary	1
tibia	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP6AP2	295	ubiquitous	marker	visceral pleura, tibia, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP6AP2	2,236

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP6AP2	O75787	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	671.8×	0.002	ATP6AP2
Metabolism of Angiotensinogen to Angiotensins	1	634.4×	0.002	ATP6AP2
Neutrophil degranulation	1	23.1×	0.043	ATP6AP2

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
eye pigmentation	1	16852.0×	9e-04	ATP6AP2
central nervous system maturation	1	8426.0×	9e-04	ATP6AP2
rostrocaudal neural tube patterning	1	5617.3×	9e-04	ATP6AP2
positive regulation of transforming growth factor beta1 production	1	2808.7×	0.001	ATP6AP2
head morphogenesis	1	2106.5×	0.001	ATP6AP2
Golgi lumen acidification	1	1685.2×	0.001	ATP6AP2
angiotensin maturation	1	1296.3×	0.001	ATP6AP2
endosomal lumen acidification	1	1203.7×	0.001	ATP6AP2
intracellular pH reduction	1	1203.7×	0.001	ATP6AP2
synaptic vesicle lumen acidification	1	936.2×	0.002	ATP6AP2
vacuolar acidification	1	732.7×	0.002	ATP6AP2
lysosomal lumen acidification	1	674.1×	0.002	ATP6AP2
regulation of MAPK cascade	1	455.5×	0.003	ATP6AP2
positive regulation of Wnt signaling pathway	1	383.0×	0.003	ATP6AP2
proton transmembrane transport	1	312.1×	0.003	ATP6AP2
positive regulation of canonical Wnt signaling pathway	1	154.6×	0.006	ATP6AP2

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
ATP6AP2	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	ATP6AP2

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)
ATP6AP2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.