ANKRD54

Chr 22

ankyrin repeat domain 54

Also known as: LIAR

The ANKRD54 protein regulates intracellular signaling events during erythroid terminal differentiation and is predicted to have protein kinase regulator activity. Mutations cause autosomal recessive intellectual disability with seizures and growth retardation, typically presenting in early childhood. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.83
Clinical SummaryANKRD54
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.002
Z-score 2.06
OE 0.44 (0.250.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.93Z-score
OE missense 0.78 (0.670.92)
117 obs / 149.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.250.83)
00.351.4
Missense OE0.78 (0.670.92)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 7 / 15.9Missense obs/exp: 117 / 149.1Syn Z: -0.86
DN
0.6743th %ile
GOF
0.6931th %ile
LOF
0.3453th %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

ANKRD54 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗