ANKS3

Chr 16

ankyrin repeat and sterile alpha motif domain containing 3

NCBI Gene: 124401 ENSG00000168096 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be located in cytoplasm. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.73

Clinical Summary— ANKS3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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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 OE?0.48 (0.33–0.73)

0≤0.351.4

Missense OE?1.25 (1.16–1.34)

0≤0.61.4

Synonymous OE?1.38

0≤1.21.6

LoF obs/exp: 17 / 35.1Missense obs/exp: 497 / 398.3Syn Z: -3.89

This gene — mechanism propensity

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.