MS4A7

Chr 11

membrane spanning 4-domains A7

Also known as: 4SPAN2, CD20L4, CFFM4, MS4A8

NCBI Gene: 58475ENSG00000166927UniProt: Q9GZW8

This gene encodes a member of the membrane-spanning 4A gene family, members of which are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns in hematopoietic cells and nonlymphoid tissues. This family member is associated with mature cellular function in the monocytic lineage, and it may be a component of a receptor complex involved in signal transduction. This gene is localized to 11q12, in a cluster of other family members. At least four alternatively spliced transcript variants encoding two distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

59
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MS4A7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 45 VUS of 59 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.
1.51LOEUF
pLI 0.000
Z-score 0.38
OE 0.87 (0.52–1.51)
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.
-0.02Z-score
OE missense 1.01 (0.87–1.17)
123 obs / 122.2 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.0.87 (0.52–1.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.87–1.17)
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: 9 / 10.3Missense obs/exp: 123 / 122.2Syn Z: 0.18

ClinVar Variant Classifications

59 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic4
VUS45
Likely Benign4
6
Pathogenic
4
Likely Pathogenic
45
VUS
4
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
42
3
0
45
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total04514059

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

View in ClinVar →

Protein Context — Lollipop Plot

MS4A7 · 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
Hepatic danger signaling triggers TREM2(+) macrophage induction and drives steatohepatitis via MS4A7-dependent inflammasome activation.
Zhou L et al.·Sci Transl Med
2024
Lipid droplet efferocytosis attenuates proinflammatory signaling in macrophages via TREM2- and MS4A7-dependent mechanisms.
Zhou L et al.·Cell Rep
2025Functional
The short isoform of MS4A7 is a novel player in glioblastoma microenvironment, M2 macrophage polarization, and tumor progression.
Ni B et al.·J Neuroinflammation
2023
Model for predicting immunotherapy based on M2 macrophage infiltration in TNBC.
Wu H et al.·Front Immunol
2023Functional
Molecular autopsy in maternal-fetal medicine.
Shamseldin HE et al.·Genet Med
2018
Specific expression and common potential therapeutic drugs in different brain regions of major depressive disorder patients: bioinformatics analysis.
Chen N et al.·J Affect Disord
2025Cohort
A single-cell atlas of RNA alternative splicing in the glioma-immune ecosystem.
Song X et al.·Genome Biol
2025
A novel iTreg-related signature for prognostic prediction in lung adenocarcinoma.
Zhang J et al.·Cancer Sci
2024
Integrated analysis of tumor-associated macrophage infiltration and prognosis in ovarian cancer.
Tan Q et al.·Aging (Albany NY)
2021
Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to Treatment.
Lefaucheur C et al.·J Am Soc Nephrol
2018
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