ANKS3

Chr 16

ankyrin repeat and sterile alpha motif domain containing 3

NCBI Gene: 124401ENSG00000168096UniProt: Q6ZW76OMIM: 617310

The ANKS3 protein is predicted to function in the cilium and may be involved in vasopressin signaling in the kidney. Mutations cause autosomal recessive nephronophthisis, a ciliopathy characterized by chronic kidney disease that typically progresses to end-stage renal disease in childhood or adolescence. This gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.73
Clinical Summary— ANKS3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 8 VUS of 39 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.73LOEUF
pLI 0.000
Z-score 2.83
OE 0.48 (0.33–0.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.76Z-score
OE missense 1.25 (1.16–1.34)
497 obs / 398.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.48 (0.33–0.73)
0≤0.351.4
Missense OE1.25 (1.16–1.34)
0≤0.61.4
Synonymous OE1.38
0≤1.21.6
LoF obs/exp: 17 / 35.1Missense obs/exp: 497 / 398.3Syn Z: -3.89
DN
0.6840th %ile
GOF
0.6735th %ile
LOF
0.3357th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

39 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
VUS8
Likely Benign2
Benign4
25
Pathogenic
8
VUS
2
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
24
0
25
Likely Pathogenic
0
0
0
0
0
VUS
0
2
6
0
8
Likely Benign
0
1
0
1
2
Benign
0
1
0
3
4
Total1430439

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ANKS3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients