Nephronophthisis 19

Summary

Nephronophthisis 19 (MONDO:0014537) is a disease caused by DCDC2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: DCDC2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 91

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephronophthisis 19
Mondo ID	MONDO:0014537
OMIM	616217
DOID	DOID:0111126
UMLS	C4015542
MedGen	863979
GARD	0018081
Is cancer (heuristic)	no

Also known as: DCDC2 nephronophthisis (disease) · nephronophthisis (disease) caused by mutation in DCDC2 · nephronophthisis 19 · nephronophthisis type 19 · NPHP19

Data availability: 91 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › nephronophthisis › nephronophthisis 19

Related subtypes (17): nephronophthisis 1, nephronophthisis 2, nephronophthisis 3, nephronophthisis 4, nephronophthisis 7, nephronophthisis-like nephropathy 1, nephronophthisis 11, nephronophthisis 12, nephronophthisis 9, nephronophthisis 13, nephronophthisis 14, nephronophthisis 15, nephronophthisis 16, nephronophthisis 18, nephronophthisis 20, late-onset nephronophthisis, nephronophthisis-like nephropathy 2

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

91 retrieved; paginated sample, class counts are floors:

61 uncertain significance, 7 pathogenic, 6 likely pathogenic, 4 benign, 4 benign/likely benign, 4 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
180687	NM_016356.5(DCDC2):c.649A>T (p.Lys217Ter)	DCDC2	Pathogenic	no assertion criteria provided
180689	NM_016356.5(DCDC2):c.349-2A>G	DCDC2	Pathogenic	criteria provided, multiple submitters, no conflicts
2634418	NM_016356.5(DCDC2):c.705-2A>G	DCDC2	Pathogenic	criteria provided, multiple submitters, no conflicts
417768	NM_016356.5(DCDC2):c.890T>A (p.Leu297Ter)	DCDC2	Pathogenic	criteria provided, multiple submitters, no conflicts
417769	NM_016356.5(DCDC2):c.529dup (p.Ile177fs)	DCDC2	Pathogenic	criteria provided, multiple submitters, no conflicts
501347	NM_016356.5(DCDC2):c.383C>G (p.Ser128Ter)	DCDC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
501471	NM_016356.5(DCDC2):c.942del (p.Gly315fs)	DCDC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
502281	NM_016356.5(DCDC2):c.294-2A>G	DCDC2	Pathogenic	criteria provided, multiple submitters, no conflicts
595088	NM_016356.5(DCDC2):c.970dup (p.Ala324fs)	DCDC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
180688	NM_016356.5(DCDC2):c.123_124del (p.Ser42fs)	KAAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
3064075	NM_016356.5(DCDC2):c.901C>T (p.Gln301Ter)	DCDC2	Likely pathogenic	criteria provided, single submitter
3593426	NM_016356.5(DCDC2):c.604G>T (p.Glu202Ter)	DCDC2	Likely pathogenic	criteria provided, single submitter
3593429	NM_016356.5(DCDC2):c.289_292del (p.Leu97fs)	DCDC2	Likely pathogenic	criteria provided, single submitter
804454	NM_016356.5(DCDC2):c.549dup (p.Val184fs)	DCDC2	Likely pathogenic	criteria provided, single submitter
917935	NM_016356.5(DCDC2):c.223_293del (p.Arg75fs)	DCDC2	Likely pathogenic	no assertion criteria provided
3593435	NM_016356.5(DCDC2):c.38dup (p.Pro14fs)	KAAG1	Likely pathogenic	criteria provided, single submitter
2175411	NM_016356.5(DCDC2):c.1327-15T>A	DCDC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3351296	NM_016356.5(DCDC2):c.558G>C (p.Arg186Ser)	DCDC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
596110	NM_016356.5(DCDC2):c.1066G>A (p.Ala356Thr)	DCDC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
838322	NM_016356.5(DCDC2):c.349G>A (p.Val117Ile)	DCDC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033408	NM_016356.5(DCDC2):c.278C>A (p.Ala93Asp)	DCDC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1035839	NM_016356.5(DCDC2):c.685A>G (p.Thr229Ala)	DCDC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1175738	NM_016356.5(DCDC2):c.1018G>A (p.Asp340Asn)	DCDC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1338443	NM_016356.5(DCDC2):c.840AGA[1] (p.Glu281del)	DCDC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1342839	NM_016356.5(DCDC2):c.967G>C (p.Gly323Arg)	DCDC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1416245	NM_016356.5(DCDC2):c.1071C>A (p.Asn357Lys)	DCDC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1704142	NM_016356.5(DCDC2):c.1028C>T (p.Pro343Leu)	DCDC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2066584	NM_016356.5(DCDC2):c.1165G>A (p.Glu389Lys)	DCDC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2187708	NM_016356.5(DCDC2):c.1056T>G (p.Asp352Glu)	DCDC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2336708	NM_016356.5(DCDC2):c.209C>A (p.Thr70Asn)	DCDC2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 3 · 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
DCDC2	Strong	Autosomal recessive	nephronophthisis 19	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DCDC2	Orphanet:480556	Isolated neonatal sclerosing cholangitis
DCDC2	Orphanet:84081	Senior-Boichis syndrome
DCDC2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

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
DCDC2	HGNC:18141	ENSG00000146038	Q9UHG0	Doublecortin domain-containing protein 2	gencc,clinvar
KAAG1	HGNC:21031	ENSG00000146049	Q9UBP8	Kidney-associated antigen 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCDC2	Doublecortin domain-containing protein 2	Protein that plays a role in the inhibition of canonical Wnt signaling pathway.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DCDC2	Other/Unknown	no		Doublecortin_dom, DCDC2_DCX_dom2, Doublecortin_dom_sf
KAAG1	Other/Unknown	no		KAAG1

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
oviduct epithelium	1
secondary oocyte	1
buccal mucosa cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
metanephros cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCDC2	156	broad	marker	secondary oocyte, oocyte, oviduct epithelium
KAAG1	40		yes	male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DCDC2	1,025
KAAG1	169

Intra-cohort edges

A	B	Sources
DCDC2	KAAG1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DCDC2	Q9UHG0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KAAG1	Q9UBP8	60.43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of Wnt signaling pathway	1	443.5×	0.012	DCDC2
regulation of cilium assembly	1	300.9×	0.012	DCDC2
dendrite morphogenesis	1	216.1×	0.012	DCDC2
positive regulation of smoothened signaling pathway	1	210.7×	0.012	DCDC2
cellular defense response	1	159.0×	0.013	DCDC2
neuron migration	1	66.9×	0.025	DCDC2
sensory perception of sound	1	50.5×	0.028	DCDC2
cilium assembly	1	36.8×	0.034	DCDC2
immune response	1	23.5×	0.047	KAAG1
intracellular signal transduction	1	19.1×	0.052	DCDC2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
DCDC2	0	0
KAAG1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	DCDC2, KAAG1

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)
DCDC2	0	—
KAAG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.