AKAIN1

Chr 18

A-kinase anchor inhibitor 1

Also known as: C18orf42

The AKAIN1 protein binds to type II regulatory subunits of protein kinase A and may interfere with A-kinase anchoring protein-mediated subcellular localization of PKA. Based on current evidence, no definitive disease associations have been established for AKAIN1 mutations. The gene shows moderate tolerance to loss-of-function variants (pLI = 0.49, LOEUF = 1.42), suggesting it may not be essential for normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
124
P/LP submissions
P/LP missense
1.42
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryAKAIN1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
119 unique Pathogenic / Likely Pathogenic· 11 VUS of 133 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.42LOEUF
pLI 0.489
Z-score 1.26
OE 0.00 (0.001.42)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.68Z-score
OE missense 0.69 (0.510.96)
26 obs / 37.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.001.42)
00.351.4
Missense OE0.69 (0.510.96)
00.61.4
Synonymous OE0.63
01.21.6
LoF obs/exp: 0 / 1.8Missense obs/exp: 26 / 37.7Syn Z: 1.10
DN
0.7132th %ile
GOF
0.82top 10%
LOF
0.3259th %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

133 submitted variants in ClinVar

Classification Summary

Pathogenic118
Likely Pathogenic1
VUS11
Likely Benign3
118
Pathogenic
1
Likely Pathogenic
11
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
118
Likely Pathogenic
1
VUS
11
Likely Benign
3
Benign
0
Total133

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AKAIN1 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found