Nephronophthisis 7

Summary

Nephronophthisis 7 (MONDO:0012680) is a disease caused by GLIS2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GLIS2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 189

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephronophthisis 7
Mondo ID	MONDO:0012680
MeSH	C566930
OMIM	611498
DOID	DOID:0111116
UMLS	C1969092
MedGen	369409
GARD	0024879
Is cancer (heuristic)	no

Also known as: GLIS2 nephronophthisis (disease) · nephronophthisis (disease) caused by mutation in GLIS2 · nephronophthisis 7 · nephronophthisis type 7 · NPHP7

Data availability: 189 ClinVar variants · 4 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 7

Related subtypes (17): nephronophthisis 1, nephronophthisis 2, nephronophthisis 3, nephronophthisis 4, nephronophthisis-like nephropathy 1, nephronophthisis 11, nephronophthisis 12, nephronophthisis 9, nephronophthisis 13, nephronophthisis 14, nephronophthisis 15, nephronophthisis 16, nephronophthisis 18, nephronophthisis 19, 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

189 retrieved; paginated sample, class counts are floors:

136 uncertain significance, 17 conflicting classifications of pathogenicity, 14 benign, 11 likely benign, 9 benign/likely benign, 1 not provided, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
242364	NM_032575.3(GLIS2):c.775+1G>T	GLIS2	Pathogenic	no assertion criteria provided
1299703	NM_032575.3(GLIS2):c.570_584del (p.Asn190_Val194del)	GLIS2	Conflicting classifications of pathogenicity	no assertion criteria provided
195389	NM_032575.3(GLIS2):c.239A>T (p.Asp80Val)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216802	NM_032575.3(GLIS2):c.1105G>A (p.Gly369Ser)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
220046	NM_032575.3(GLIS2):c.1180G>A (p.Gly394Ser)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241704	NM_032575.3(GLIS2):c.1539G>A (p.Pro513=)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
282353	NM_032575.3(GLIS2):c.693C>T (p.Asn231=)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
319210	NM_032575.3(GLIS2):c.291G>A (p.Ser97=)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
319217	NM_032575.3(GLIS2):c.1128C>T (p.Pro376=)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
319218	NM_032575.3(GLIS2):c.1326C>T (p.Ala442=)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
319224	NM_032575.3(GLIS2):c.1431C>T (p.Pro477=)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
319226	NM_032575.3(GLIS2):c.1569G>A (p.Val523=)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3520579	NM_032575.3(GLIS2):c.1338G>T (p.Lys446Asn)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3580730	NM_032575.3(GLIS2):c.1414T>C (p.Cys472Arg)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
885386	NM_032575.3(GLIS2):c.346-4C>G	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
887478	NM_032575.3(GLIS2):c.546G>A (p.Leu182=)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
887666	NM_032575.3(GLIS2):c.903C>T (p.His301=)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
887667	NM_032575.3(GLIS2):c.1033G>A (p.Gly345Ser)	GLIS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1025251	NM_032575.3(GLIS2):c.1559C>T (p.Pro520Leu)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1028964	NM_032575.3(GLIS2):c.1244C>T (p.Pro415Leu)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1367895	NM_032575.3(GLIS2):c.1129G>A (p.Gly377Ser)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1416713	NM_032575.3(GLIS2):c.100C>T (p.Arg34Cys)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1430984	NM_032575.3(GLIS2):c.164C>T (p.Pro55Leu)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1441797	NM_032575.3(GLIS2):c.1564G>A (p.Val522Met)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1520723	NM_032575.3(GLIS2):c.1475C>T (p.Thr492Met)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1946694	NM_032575.3(GLIS2):c.1111C>A (p.Pro371Thr)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2047699	NM_032575.3(GLIS2):c.628G>A (p.Ala210Thr)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2065864	NM_032575.3(GLIS2):c.1327G>A (p.Glu443Lys)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2143453	NM_032575.3(GLIS2):c.1004C>G (p.Pro335Arg)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2244525	NM_032575.3(GLIS2):c.275C>T (p.Pro92Leu)	GLIS2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
GLIS2	Strong	Autosomal recessive	nephronophthisis 7	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GLIS2	Orphanet:329469	Acute megakaryoblastic leukemia in children without Down syndrome
GLIS2	Orphanet:93592	Juvenile nephronophthisis

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
GLIS2	HGNC:29450	ENSG00000126603	Q9BZE0	Zinc finger protein GLIS2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GLIS2	Zinc finger protein GLIS2	Can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context.

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)
GLIS2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like

Expression context

Cohort genes with no expression data: 0.

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
ascending aorta	1
metanephros cortex	1
right coronary artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GLIS2	134	ubiquitous	yes	right coronary artery, metanephros cortex, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GLIS2	1,690

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GLIS2	Q9BZE0	55.47

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
cell differentiation involved in kidney development	1	5617.3×	0.002	GLIS2
hematopoietic stem cell homeostasis	1	561.7×	0.006	GLIS2
negative regulation of smoothened signaling pathway	1	455.5×	0.006	GLIS2
positive regulation of protein localization to nucleus	1	391.9×	0.006	GLIS2
central nervous system development	1	115.4×	0.016	GLIS2
negative regulation of DNA-templated transcription	1	31.6×	0.046	GLIS2
positive regulation of DNA-templated transcription	1	27.9×	0.046	GLIS2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.063	GLIS2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	GLIS2

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
GLIS2	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	GLIS2

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)
GLIS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.