Ensembl is currently experiencing issues

The Ensembl REST API is temporarily unavailable. Some gene data (transcript details, protein domains) may be incomplete. Other data sources are unaffected.

You can check Ensembl's status at status.ensembl.org

PALM2

Chr 9

paralemmin 2

Also known as: AKAP2

The protein binds to the regulatory subunit of protein kinase A and modulates actin cytoskeleton structure, functioning in cellular polarity and cAMP signaling pathways. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in early infancy. The gene shows tolerance to loss-of-function variants in the general population, suggesting complete loss of function may be required for disease manifestation.

OMIMResearchSummary from UniProt
MultiplemechanismLOEUF 0.74
Clinical SummaryPALM2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 400 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/PALM2?content-type=application/json&expand=1

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.001
Z-score 2.40
OE 0.41 (0.240.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.05Z-score
OE missense 0.81 (0.710.91)
184 obs / 228.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.240.74)
00.351.4
Missense OE0.81 (0.710.91)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 8 / 19.4Missense obs/exp: 184 / 228.5Syn Z: -0.12
DN
0.76top 25%
GOF
0.73top 25%
LOF
0.3065th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

PALM2 · 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 →