MARCKS

Chr 6

myristoylated alanine rich protein kinase C substrate

Also known as: 80K-L, MACS, PKCSL, PRKCSL

NCBI Gene: 4082ENSG00000277443UniProt: P29966

The protein encoded by this gene is a substrate for protein kinase C. It is localized to the plasma membrane and is an actin filament crosslinking protein. Phosphorylation by protein kinase C or binding to calcium-calmodulin inhibits its association with actin and with the plasma membrane, leading to its presence in the cytoplasm. The protein is thought to be involved in cell motility, phagocytosis, membrane trafficking and mitogenesis. [provided by RefSeq, Jul 2008]

115
ClinVar variants
23
Pathogenic / LP
0.33
pLI score
0
Active trials
Clinical Summary— MARCKS
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 86 VUS of 115 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.10LOEUF
pLI 0.326
Z-score 1.47
OE 0.23 (0.08–1.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.29Z-score
OE missense 0.92 (0.79–1.09)
104 obs / 112.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.23 (0.08–1.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.79–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 1 / 4.3Missense obs/exp: 104 / 112.7Syn Z: 0.80

ClinVar Variant Classifications

115 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic4
VUS86
Likely Benign3
Benign3
19
Pathogenic
4
Likely Pathogenic
86
VUS
3
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
1
0
3
0
4
VUS
0
82
4
0
86
Likely Benign
0
1
0
2
3
Benign
0
2
1
0
3
Total185272115

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

View in ClinVar →

Protein Context — Lollipop Plot

MARCKS · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis.
Huang XZ et al.·Nat Commun
2023
Integrating single-cell and bulk RNA sequencing data unveils antigen presentation and process-related CAFS and establishes a predictive signature in prostate cancer.
Wang W et al.·J Transl Med
2024
MARCKS and Lung Disease.
Sheats MK et al.·Am J Respir Cell Mol Biol
2019Review
Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders.
Kaiyrzhanov R et al.·Brain
2024
Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes.
Mei Z et al.·Alzheimers Dement
2025
Shared genetic risk loci between Alzheimer's disease and related dementias, Parkinson's disease, and amyotrophic lateral sclerosis.
Wainberg M et al.·Alzheimers Res Ther
2023
Neurobiology of lithium: an update.
Lenox RH et al.·J Clin Psychiatry
1998Review
Investigating cellular similarities and differences between upper tract urothelial carcinoma and bladder urothelial carcinoma using single-cell sequencing.
Zhang Q et al.·Front Immunol
2024
Optogenetic modulation in stroke recovery.
Pendharkar AV et al.·Neurosurg Focus
2016Review
Treatment of airway mucus hypersecretion.
Rogers DF et al.·Ann Med
2006Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools