MS4A4E

Chr 11

membrane spanning 4-domains A4E

NCBI Gene: 643680ENSG00000214787UniProt: Q96PG1

Most MS4A genes, including MS4A4E, encode proteins with at least 4 potential transmembrane domains and N- and C-terminal cytoplasmic domains encoded by distinct exons.[supplied by OMIM, Apr 2004]

14
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MS4A4E
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 3 VUS of 14 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.
1.89LOEUF
pLI 0.001
Z-score -0.31
OE 1.18 (0.55–1.89)
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.
0.21Z-score
OE missense 0.90 (0.69–1.20)
34 obs / 37.6 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.1.18 (0.55–1.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.69–1.20)
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.0.97
0≤1.21.6
LoF obs/exp: 4 / 3.4Missense obs/exp: 34 / 37.6Syn Z: 0.09

ClinVar Variant Classifications

14 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic4
VUS3
Likely Benign1
6
Pathogenic
4
Likely Pathogenic
3
VUS
1
Likely Benign

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————6
Likely Pathogenic
————4
VUS
————3
Likely Benign
————1
Benign
————0
Total—14

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MS4A4E · 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
Genomics of Alzheimer Disease: A Review.
Rosenberg RN et al.·JAMA Neurol
2016Review
Population-based analysis of Alzheimer's disease risk alleles implicates genetic interactions.
Ebbert MT et al.·Biol Psychiatry
2014
Pharmacogenomics of Alzheimer's Disease: Novel Strategies for Drug Utilization and Development.
Cacabelos R et al.·Methods Mol Biol
2022
Association of genetic risk factors with cognitive decline: the PATH through life project.
Andrews SJ et al.·Neurobiol Aging
2016
Late Onset Alzheimer's Disease Risk Variants in Cognitive Decline: The PATH Through Life Study.
Andrews SJ et al.·J Alzheimers Dis
2017
Relationship between Alzheimer's disease GWAS-linked top hits and risk of Parkinson's disease with or without cognitive decline: a Chinese population-based study.
Wang YQ et al.·Neurobiol Aging
2016
Genome-wide association study identifies multiple novel loci associated with disease progression in subjects with mild cognitive impairment.
Hu X et al.·Transl Psychiatry
2011
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