PALM2AKAP2

Chr 9

PALM2 and AKAP2 fusion

Also known as: AKAP-KL, AKAP2, AKAPKL, MISP2, PALM2, PALM2-AKAP2, PRKA2

The AKAP2 isoform binds to the regulatory subunit of protein kinase A and modulates actin cytoskeleton structure, potentially establishing cellular polarity and integrating PKA signaling with downstream effectors. This gene is highly constrained against loss-of-function variants (pLI nearly 1.0, LOEUF 0.527), but no specific disease associations have been established in the provided data. The gene produces three distinct protein isoforms including PALM2, AKAP2, and a PALM2-AKAP2 fusion protein of unknown biological significance.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.53
Clinical SummaryPALM2AKAP2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.000
Z-score 4.11
OE 0.35 (0.230.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.23Z-score
OE missense 0.97 (0.911.04)
601 obs / 616.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.230.53)
00.351.4
Missense OE0.97 (0.911.04)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 16 / 46.1Missense obs/exp: 601 / 616.7Syn Z: 0.10
DN
0.7326th %ile
GOF
0.77top 25%
LOF
0.3647th %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

PALM2AKAP2 · 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.

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Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found