ANKRD23

Chr 2

ankyrin repeat domain 23

Also known as: DARP, MARP3

NCBI Gene: 200539ENSG00000163126UniProt: Q86SG2

The protein is a nuclear transcriptional regulator that may link myofibrillar stretch-induced signaling to muscle gene expression and energy metabolism. Mutations cause autosomal recessive dilated cardiomyopathy with left ventricular noncompaction. This gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
31
P/LP submissions
0%
P/LP missense
1.88
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ANKRD23
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 84 VUS of 129 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
1.88LOEUF
pLI 0.000
Z-score -1.62
OE 1.43 (1.03–1.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.58Z-score
OE missense 0.88 (0.77–1.00)
154 obs / 175.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.43 (1.03–1.88)
0≤0.351.4
Missense OE0.88 (0.77–1.00)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 24 / 16.8Missense obs/exp: 154 / 175.6Syn Z: 0.51
DN
0.6357th %ile
GOF
0.72top 25%
LOF
0.4134th %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

129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic10
VUS84
Likely Benign6
21
Pathogenic
10
Likely Pathogenic
84
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
10
0
10
VUS
0
54
30
0
84
Likely Benign
0
4
2
0
6
Benign
0
0
0
0
0
Total058630121

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

View in ClinVar →

Protein Context — Lollipop Plot

ANKRD23 · protein map & ClinVar variants

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

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
Molecular Profiling of DNA Methylation and Alternative Splicing of Genes in Skeletal Muscle of Obese Rabbits
Li Y et al.·Curr Issues Mol Biol
2021
Preliminary Results about Lamb Meat Tenderness Based on the Study of Novel Isoforms and Alternative Splicing Regulation Pathways Using Iso-seq, RNA-seq and CTCF ChIP-seq Data
Yuan Z et al.·Foods
2022
Shared and Sex-Specific Genetic Risk for Parkinson's Disease Risk Across European Populations.
Global Parkinson’s Genetics Program (GP2) et al.·medRxiv
2026
Association between dietary fructose and human colon DNA methylation: implication for racial disparities in colorectal cancer risk using a cross-sectional study.
Devall MA et al.·Am J Clin Nutr
2025
Weighted gene co-expression network-based approach to identify key genes associated with anthracycline-induced cardiotoxicity and construction of miRNA-transcription factor-gene regulatory network
Wan G et al.·Mol Med
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 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