Nephronophthisis 16

Summary

Nephronophthisis 16 (MONDO:0014158) is a disease caused by ANKS6 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ANKS6 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 440

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephronophthisis 16
Mondo ID	MONDO:0014158
OMIM	615382
DOID	DOID:0111124
SNOMED CT	444558002
UMLS	C3809320
MedGen	815650
GARD	0018183
Is cancer (heuristic)	no

Also known as: ANKS6 nephronophthisis (disease) · nephronophthisis (disease) caused by mutation in ANKS6 · nephronophthisis 16 · nephronophthisis type 16 · NPHP16

Data availability: 440 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 16

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 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

440 retrieved; paginated sample, class counts are floors:

215 uncertain significance, 133 likely benign, 22 conflicting classifications of pathogenicity, 21 benign/likely benign, 19 pathogenic, 15 benign, 12 likely pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031266	NM_173551.5(ANKS6):c.907+2T>A	ANKS6	Pathogenic	criteria provided, single submitter
1695916	NM_173551.5(ANKS6):c.1672_1675dup (p.Pro559fs)	ANKS6	Pathogenic	criteria provided, single submitter
1710087	NM_173551.5(ANKS6):c.1373G>A (p.Trp458Ter)	ANKS6	Pathogenic	no assertion criteria provided
2029697	NM_173551.5(ANKS6):c.1300del (p.Leu434fs)	ANKS6	Pathogenic	criteria provided, single submitter
2183268	NM_173551.5(ANKS6):c.639G>A (p.Trp213Ter)	ANKS6	Pathogenic	criteria provided, single submitter
2681749	NM_173551.5(ANKS6):c.651dup (p.Asn218fs)	ANKS6	Pathogenic	criteria provided, single submitter
2881274	NM_173551.5(ANKS6):c.189_190del (p.Ala64fs)	ANKS6	Pathogenic	criteria provided, single submitter
2883386	NM_173551.5(ANKS6):c.1683_1698dup (p.Phe567fs)	ANKS6	Pathogenic	criteria provided, single submitter
2982283	NM_173551.5(ANKS6):c.1096C>T (p.Gln366Ter)	ANKS6	Pathogenic	criteria provided, single submitter
3596087	NM_173551.5(ANKS6):c.864del (p.Asp288fs)	ANKS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3661824	NM_173551.5(ANKS6):c.1510dup (p.Gln504fs)	ANKS6	Pathogenic	criteria provided, single submitter
3686362	NM_173551.5(ANKS6):c.154del (p.Ala52fs)	ANKS6	Pathogenic	criteria provided, single submitter
4740223	NM_173551.5(ANKS6):c.433del (p.Ala145fs)	ANKS6	Pathogenic	criteria provided, single submitter
571622	NM_173551.5(ANKS6):c.727C>T (p.Gln243Ter)	ANKS6	Pathogenic	criteria provided, single submitter
574976	NM_173551.5(ANKS6):c.694_718dup (p.Val240fs)	ANKS6	Pathogenic	criteria provided, single submitter
579608	NM_173551.5(ANKS6):c.1381C>T (p.Arg461Ter)	ANKS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
591737	NM_173551.5(ANKS6):c.130_157del (p.Glu44fs)	ANKS6	Pathogenic	criteria provided, single submitter
64356	NM_173551.5(ANKS6):c.1973-3C>G	ANKS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
64357	NM_173551.5(ANKS6):c.2054_2064del (p.His685fs)	ANKS6	Pathogenic	no assertion criteria provided
64358	NM_173551.5(ANKS6):c.2370_2372del (p.Tyr790_Gln791delinsTer)	ANKS6	Pathogenic	criteria provided, multiple submitters, no conflicts
64359	NM_173551.5(ANKS6):c.2512-2A>C	ANKS6	Pathogenic	no assertion criteria provided
661012	NM_173551.5(ANKS6):c.539_540del (p.Leu180fs)	ANKS6	Pathogenic	criteria provided, single submitter
1175179	NM_173551.5(ANKS6):c.2420dup (p.Thr808fs)	ANKS6	Likely pathogenic	criteria provided, single submitter
1175180	NM_173551.5(ANKS6):c.1973-1G>A	ANKS6	Likely pathogenic	criteria provided, single submitter
1710088	NM_173551.5(ANKS6):c.2394+1G>A	ANKS6	Likely pathogenic	criteria provided, single submitter
2501784	NM_173551.5(ANKS6):c.2142G>T (p.Lys714Asn)	ANKS6	Likely pathogenic	criteria provided, single submitter
3596035	NM_173551.5(ANKS6):c.2041C>T (p.Gln681Ter)	ANKS6	Likely pathogenic	criteria provided, single submitter
3596039	NM_173551.5(ANKS6):c.1965_1966delinsA (p.Asn655fs)	ANKS6	Likely pathogenic	criteria provided, single submitter
3596071	NM_173551.5(ANKS6):c.1318C>T (p.Arg440Ter)	ANKS6	Likely pathogenic	criteria provided, single submitter
3596086	NM_173551.5(ANKS6):c.877C>T (p.Arg293Ter)	ANKS6	Likely pathogenic	criteria provided, single submitter

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
ANKS6	Definitive	Autosomal recessive	nephronophthisis 16	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANKS6	Orphanet:93591	Infantile nephronophthisis
ANKS6	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
ANKS6	HGNC:26724	ENSG00000165138	Q68DC2	Ankyrin repeat and SAM domain-containing protein 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANKS6	Ankyrin repeat and SAM domain-containing protein 6	Required for renal function.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANKS6	Scaffold/PPI	no		SAM, Ankyrin_rpt, SAM/pointed_sf

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANKS6	202	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANKS6	1,262

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANKS6	Q68DC2	1

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
determination of left/right symmetry	1	255.3×	0.014	ANKS6
kidney development	1	140.4×	0.014	ANKS6
heart development	1	78.8×	0.014	ANKS6
in utero embryonic development	1	72.0×	0.014	ANKS6

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
ANKS6	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	ANKS6

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)
ANKS6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.