ANKRD17

Chr 4AD

ankyrin repeat domain 17

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

NCBI Gene: 26057 ENSG00000132466 UniProt: O75179 OMIM: 615929

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene belongs to the family of ankyrin repeat-containing proteins, and contains two distinct arrays of ankyrin repeats in its amino-terminal region, one with 15 ankyrin repeats, and the other with 10 ankyrin repeats. It also contains a nuclear export signal, nuclear localization signal, and a cyclin-binding RXL motif. Localization of this protein to the nucleus has been shown experimentally, and interactions between this protein and cyclin-dependent kinase 2 have been observed. It has been suggested that this protein plays a role in both DNA replication and in both anti-viral and anti-bacterial innate immune pathways. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.061 OMIM phenotype

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

48 unique Pathogenic / Likely Pathogenic· 427 VUS of 581 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 ↗

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 OE?0.02 (0.01–0.06)

0≤0.351.4

Missense OE?0.59 (0.56–0.63)

0≤0.61.4

Synonymous OE?0.99

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

This gene — mechanism propensity

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 · 73% of P/LP variants are LoF · LOEUF 0.06 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFHeterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism.1

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

References

1.PMID 33909992 ↗

ClinVar Variant Classifications

581 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic28

VUS427

Likely Benign55

Benign9

Conflicting3

Pathogenic

Likely Pathogenic

427

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	20	0	0	0	20
Likely Pathogenic	15	13	0	0	28
VUS	4	409	12	2	427
Likely Benign	0	30	6	19	55
Benign	0	2	1	6	9
Conflicting	—				3
Total	39	454	19	27	542

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap ANKRD17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →