ANKS6

Chr 9AR

ankyrin repeat and sterile alpha motif domain containing 6

Also known as: ANKRD14, NPHP16, PKDR1, SAMD6

The protein contains multiple ankyrin repeats and a SAM domain, localizes to the proximal region of the primary cilium, and is required for renal function and renal/cardiovascular development. Mutations cause nephronophthisis 16, a chronic tubulo-interstitial nephritis that leads to progressive kidney disease. This follows autosomal recessive inheritance.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.691 OMIM phenotype
Clinical SummaryANKS6
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Gene-Disease Validity (ClinGen)
nephronophthisis 16 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — ANKS6
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 2.89
OE 0.44 (0.290.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.08Z-score
OE missense 1.01 (0.941.09)
463 obs / 458.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.44 (0.290.69)
00.351.4
Missense OE1.01 (0.941.09)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 14 / 31.5Missense obs/exp: 463 / 458.4Syn Z: 0.12
DN
0.6551th %ile
GOF
0.6930th %ile
LOF
0.3941th %ile

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

GOFprediction above median
DNprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ANKS6 · 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

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗