ANKRD17

Chr 4

ankyrin repeat domain 17

Also known as: CAGS, GTAR, MASK2, NY-BR-16

NCBI Gene: 26057ENSG00000132466UniProt: O75179

The protein contains ankyrin repeats and localizes to the nucleus where it interacts with cyclin-dependent kinase 2 and functions in DNA replication and innate immune pathways. Loss-of-function mutations cause Chopra-Amiel-Gordon syndrome through an autosomal dominant inheritance pattern. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the disease mechanism.

GeneReviewsResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismLOEUF 0.06
Clinical Summary— ANKRD17
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Gene-Disease Validity (ClinGen)
syndromic complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 369 VUS of 509 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — ANKRD17
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.06LOEUF
pLI 1.000
Z-score 9.13
OE 0.02 (0.01–0.06)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
5.36Z-score
OE missense 0.59 (0.56–0.63)
802 obs / 1357.6 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.02 (0.01–0.06)
0≤0.351.4
Missense OE0.59 (0.56–0.63)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 2 / 101.0Missense obs/exp: 802 / 1357.6Syn Z: 0.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongANKRD17-related neurodevelopmental disorderLOFAD
DN
0.17100th %ile
GOF
0.2597th %ile
LOF
0.89top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 46% of P/LP variants are LoF · LOEUF 0.06

Literature Evidence

LOFHeterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism.PMID:33909992

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

509 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic24
VUS369
Likely Benign36
Benign4
Conflicting2
35
Pathogenic
24
Likely Pathogenic
369
VUS
36
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
20
0
35
Likely Pathogenic
12
11
1
0
24
VUS
4
345
19
1
369
Likely Benign
0
19
4
13
36
Benign
0
1
1
2
4
Conflicting
—2
Total313764516470

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

View in ClinVar →

Protein Context — Lollipop Plot

ANKRD17 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Novel ANKRD17 variants implicate synaptic and mitochondrial disruptions in intellectual disability and autism spectrum disorder.
Xia D et al.·J Neurodev Disord
2025Open Access
ANKRD17 induces pro-survival signaling pathways that enhance cellular invasion and migration during hepatocellular carcinoma tumorigenesis.
Keng VW et al.·iScience
2025Open Access
Case report: Whole exome sequencing reveals a novel splicing variant of ANKRD17 gene in a Chinese male juvenile with developmental delay and transient tic disorder.
Chen J et al.·Front Genet
2024Open AccessCase report
A case of Chopra-Amiel-Gordon syndrome with a novel heterozygous variant in the ANKRD17 gene: A case report.
Tinatin T et al.·SAGE Open Med Case Rep
2023Case report
Effect of miR-493-5p on proliferation and differentiation of myoblast by targeting ANKRD17.
Zhuang X et al.·Cell Tissue Res
2023
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