MS4A6A

Chr 11

membrane spanning 4-domains A6A

Also known as: 4SPAN3, 4SPAN3.2, CD20L3, CDA01, MS4A6, MST090, MSTP090

NCBI Gene: 64231ENSG00000110077UniProt: Q9H2W1

This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. The gene encoding this protein is localized to 11q12.1, among a cluster of family members. Alternative splicing of this gene results in several transcript variants that encode different protein isoforms. [provided by RefSeq, Oct 2011]

54
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MS4A6A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 19 VUS of 54 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.
1.95LOEUF
pLI 0.000
Z-score -1.84
OE 1.66 (1.06–1.95)
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.
-0.46Z-score
OE missense 1.11 (0.97–1.28)
144 obs / 129.4 exp
Tolerant

Tolerant to missense variation

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.1.66 (1.06–1.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (0.97–1.28)
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.1.07
0≤1.21.6
LoF obs/exp: 15 / 9.0Missense obs/exp: 144 / 129.4Syn Z: -0.38

ClinVar Variant Classifications

54 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic4
VUS19
Likely Benign7
6
Pathogenic
4
Likely Pathogenic
19
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
4
0
4
VUS
0
16
3
0
19
Likely Benign
0
6
1
0
7
Benign
0
0
0
0
0
Total02214036

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

View in ClinVar →

Protein Context — Lollipop Plot

MS4A6A · 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
MS4A6A/Ms4a6d deficiency disrupts neuroprotective microglia functions and promotes inflammation in Alzheimer's disease model.
Jiao HS et al.·Mol Neurodegener
2025Functional
MS4A6A regulates ox-LDL-induced endothelial dysfunction and monocyte adhesion in atherosclerosis via the IKK/NF-kappaB pathway.
Lu-Chen et al.·Int Immunopharmacol
2025
Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes.
Novikova G et al.·Nat Commun
2021
MS4A6A is a new prognostic biomarker produced by macrophages in glioma patients.
Zhang C et al.·Front Immunol
2022Cohort
The prevalence of CD33 and MS4A6A variant in Chinese Han population with Alzheimer's disease.
Deng YL et al.·Hum Genet
2012
Clinical features and shared mechanisms of chronic gastritis and osteoporosis.
Han T et al.·Sci Rep
2023Functional
The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer's disease risk.
Deming Y et al.·Sci Transl Med
2019
Genome-wide association study identifies Alzheimer's risk variant in MS4A6A influencing cerebrospinal fluid sTREM2 levels.
Hou XH et al.·Neurobiol Aging
2019
APOE and MS4A6A interact with GnRH signaling in Alzheimer's disease: Enrichment of epistatic effects.
Cáceres A et al.·Alzheimers Dement
2017
The GBA, DYRK1A and MS4A6A polymorphisms influence the age at onset of Chinese Parkinson patients.
Fan K et al.·Neurosci Lett
2016Cohort
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