Dent disease type 2

Summary

Dent disease type 2 (MONDO:0010359) is a disease caused by OCRL (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: OCRL (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 100

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Dent disease type 2
Mondo ID	MONDO:0010359
MeSH	C564487
OMIM	300555
Orphanet	93623
DOID	DOID:0081454
ICD-11	2053330521
SNOMED CT	717790004
UMLS	C1845167
MedGen	336867
GARD	0010645
Is cancer (heuristic)	no

Also known as: dent disease 2, X-linked recessive · Dent disease caused by mutation in OCRL · Dent disease type 2 · nephrolithiasis type 2 · OCRL Dent disease

Data availability: 100 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › renal tubular transport disease › Dent disease › Dent disease type 2

Related subtypes (1): Dent disease type 1

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

100 retrieved; paginated sample, class counts are floors:

36 uncertain significance, 18 conflicting classifications of pathogenicity, 16 pathogenic, 13 likely pathogenic, 7 benign/likely benign, 6 pathogenic/likely pathogenic, 2 likely benign, 1 not provided, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
10857	NM_000276.4(OCRL):c.2530C>T (p.Arg844Ter)	OCRL	Pathogenic	criteria provided, multiple submitters, no conflicts
10860	NM_000276.4(OCRL):c.1436A>G (p.Tyr479Cys)	OCRL	Pathogenic	no assertion criteria provided
10861	NM_000276.4(OCRL):c.952C>T (p.Arg318Cys)	OCRL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1413179	NM_000276.4(OCRL):c.2083C>T (p.Arg695Ter)	OCRL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455667	NM_000276.4(OCRL):c.953G>A (p.Arg318His)	OCRL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685996	NM_000276.4(OCRL):c.217_218del (p.Leu73fs)	OCRL	Pathogenic	criteria provided, single submitter
1685997	NM_000276.4(OCRL):c.1458G>A (p.Trp486Ter)	OCRL	Pathogenic	criteria provided, single submitter
208012	Single allele	OCRL	Pathogenic	no assertion criteria provided
208013	NG_008638.1:g.(5550_9683)_(13328_22050)del	OCRL	Pathogenic	no assertion criteria provided
2504612	NM_000276.4(OCRL):c.1467-1G>A	OCRL	Pathogenic	no assertion criteria provided
2506950	NM_000276.4(OCRL):c.1056+1G>A	OCRL	Pathogenic	no assertion criteria provided
2633832	NM_000276.4(OCRL):c.260del (p.Gln87fs)	OCRL	Pathogenic	criteria provided, multiple submitters, no conflicts
279859	NM_000276.4(OCRL):c.940-11G>A	OCRL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29972	NM_000276.4(OCRL):c.1598T>C (p.Ile533Thr)	OCRL	Pathogenic	no assertion criteria provided
29973	NM_000276.4(OCRL):c.167_168del (p.Ile56fs)	OCRL	Pathogenic	no assertion criteria provided
578751	NM_000276.4(OCRL):c.560+1G>C	OCRL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
594148	NM_000276.4(OCRL):c.2428C>T (p.Arg810Ter)	OCRL	Pathogenic	criteria provided, multiple submitters, no conflicts
641377	NM_000276.4(OCRL):c.2464C>T (p.Arg822Ter)	OCRL	Pathogenic	criteria provided, multiple submitters, no conflicts
68712	NM_000276.4(OCRL):c.1477C>T (p.Arg493Trp)	OCRL	Pathogenic	criteria provided, multiple submitters, no conflicts
932947	NM_000276.4(OCRL):c.2078C>T (p.Pro693Leu)	OCRL	Pathogenic	no assertion criteria provided
960576	NM_000276.4(OCRL):c.1244+1G>A	OCRL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
975017	NM_000276.4(OCRL):c.1245-1083G>A	OCRL	Pathogenic	no assertion criteria provided
548655	NM_005540.3(INPP5B):c.152C>T (p.Ala51Val)	INPP5B	Likely pathogenic	no assertion criteria provided
1685388	NM_000276.4(OCRL):c.1713+2T>C	OCRL	Likely pathogenic	criteria provided, single submitter
2412679	NM_000276.4(OCRL):c.108del (p.Asn36fs)	OCRL	Likely pathogenic	criteria provided, single submitter
2412785	NM_000276.4(OCRL):c.2209G>A (p.Glu737Lys)	OCRL	Likely pathogenic	criteria provided, single submitter
2500926	NM_000276.4(OCRL):c.111del (p.Gln38fs)	OCRL	Likely pathogenic	criteria provided, single submitter
3066348	NM_000276.4(OCRL):c.300del (p.Asp100fs)	OCRL	Likely pathogenic	criteria provided, single submitter
3598012	NM_000276.4(OCRL):c.561-1G>A	OCRL	Likely pathogenic	criteria provided, single submitter
3598025	NM_000276.4(OCRL):c.2136_2139delinsCT (p.Glu712fs)	OCRL	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · 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
OCRL	Definitive	X-linked	Dent disease type 2	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OCRL	Orphanet:534	Oculocerebrorenal syndrome of Lowe
OCRL	Orphanet:93623	Dent disease type 2

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
OCRL	HGNC:8108	ENSG00000122126	Q01968	Inositol polyphosphate 5-phosphatase OCRL	gencc,clinvar
INPP5B	HGNC:6077	ENSG00000204084	P32019	Type II inositol 1,4,5-trisphosphate 5-phosphatase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OCRL	Inositol polyphosphate 5-phosphatase OCRL	Catalyzes the hydrolysis of the 5-position phosphate of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-bisphosphate (PtdIns(3,4,5)P3), with the greatest catalytic activity towards PtdIns(4,5)P2.
INPP5B	Type II inositol 1,4,5-trisphosphate 5-phosphatase	Regulates phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) cellular levels by cleaving the phosphate at the 5-position producing PtdIns(4)P.

Protein-family classification

Druggable: 2 · 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
Antibody/Immunoglobulin	2	29.2×	0.001

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OCRL	Antibody/Immunoglobulin	yes	3.1.3.36	RhoGAP_dom, IPPc, Rho_GTPase_activation_prot
INPP5B	Antibody/Immunoglobulin	yes	3.1.3.36	RhoGAP_dom, IPPc, Rho_GTPase_activation_prot

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 10	1
endometrium epithelium	1
lower esophagus muscularis layer	1
endothelial cell	1
left ovary	1
mucosa of stomach	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OCRL	225	ubiquitous	marker	endometrium epithelium, Brodmann (1909) area 10, lower esophagus muscularis layer
INPP5B	228	ubiquitous	marker	endothelial cell, left ovary, mucosa of stomach

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OCRL	2,269
INPP5B	963

Intra-cohort edges

A	B	Sources
INPP5B	OCRL	intact

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OCRL	Q01968	5
INPP5B	P32019	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of IP2, IP, and Ins in the cytosol	2	761.3×	1e-05	OCRL, INPP5B
Synthesis of IP3 and IP4 in the cytosol	2	423.0×	2e-05	OCRL, INPP5B
Synthesis of PIPs at the Golgi membrane	1	317.2×	0.008	OCRL
Synthesis of PIPs at the plasma membrane	1	105.7×	0.013	OCRL
Golgi Associated Vesicle Biogenesis	1	100.2×	0.013	OCRL
RHOJ GTPase cycle	1	100.2×	0.013	OCRL
RAC3 GTPase cycle	1	59.5×	0.019	OCRL
Clathrin-mediated endocytosis	1	42.6×	0.023	OCRL

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
inositol phosphate metabolic process	2	991.3×	1e-05	OCRL, INPP5B
phosphatidylinositol dephosphorylation	2	648.1×	1e-05	OCRL, INPP5B
in utero embryonic development	2	72.0×	7e-04	OCRL, INPP5B
regulation of protein processing	1	766.0×	0.004	INPP5B
membrane organization	1	255.3×	0.007	OCRL
signal transduction	2	16.1×	0.007	OCRL, INPP5B
phosphatidylinositol biosynthetic process	1	183.2×	0.009	OCRL
flagellated sperm motility	1	58.5×	0.023	INPP5B
lipid metabolic process	1	45.8×	0.027	OCRL
cilium assembly	1	36.8×	0.030	OCRL
spermatogenesis	1	17.6×	0.056	INPP5B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
OCRL	0	0
INPP5B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
INPP5B	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
OCRL	3.1.3.36	phosphoinositide 5-phosphatase
INPP5B	3.1.3.36	phosphoinositide 5-phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	OCRL, INPP5B
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
OCRL	0	—
INPP5B	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.