MS4A1

Chr 11AR

membrane spanning 4-domains A1

Also known as: B1, Bp35, CD20, CVID5, FMC7, LEU-16, S7

NCBI Gene: 931ENSG00000156738UniProt: P11836

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. This gene encodes a B-lymphocyte surface molecule which plays a role in the development and differentiation of B-cells into plasma cells. This family member is localized to 11q12, among a cluster of family members. Alternative splicing of this gene results in two transcript variants which encode the same protein. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Immunodeficiency, common variable, 5MIM #613495
AR
237
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MS4A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 154 VUS of 237 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

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.
1.27LOEUF
pLI 0.000
Z-score 0.93
OE 0.70 (0.41–1.27)
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.
0.14Z-score
OE missense 0.97 (0.85–1.11)
151 obs / 156.0 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.0.70 (0.41–1.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.85–1.11)
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: 8 / 11.4Missense obs/exp: 151 / 156.0Syn Z: -0.42

ClinVar Variant Classifications

237 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic4
VUS154
Likely Benign62
Benign8
6
Pathogenic
4
Likely Pathogenic
154
VUS
62
Likely Benign
8
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
8
132
14
0
154
Likely Benign
1
2
24
35
62
Benign
0
0
4
4
8
Total91345239234

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

View in ClinVar →

Protein Context — Lollipop Plot

MS4A1 · 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

?Immunodeficiency, common variable, 5

MIM #613495

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MS4A1 regulates M1-polarized tumor-associated macrophage infiltration, angiogenesis, and cancer progression through the HIPPO pathway in lung adenocarcinoma.
Gao W et al.·Cancer Immunol Immunother
2025
Evaluation of non-invasive biomarkers of kidney allograft rejection in a prospective multicenter unselected cohort study (EU-TRAIN).
Goutaudier V et al.·Kidney Int
2024Cohort
PerC B-Cells Activation via Thermogenetics-Based CXCL12 Generator for Intraperitoneal Immunity Against Metastatic Disseminated Tumor Cells.
Yin Z et al.·Adv Mater
2025
MS4A1 as a Potential Independent Prognostic Factor of Breast Cancer Related to Lipid Metabolism and Immune Microenvironment Based on TCGA Database Analysis.
Li S et al.·Med Sci Monit
2022
Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial.
Strømland PP et al.·Sci Rep
2025Clinical trial
Two inflammation-related genes model could predict risk in prognosis of patients with lung adenocarcinoma.
Yang W et al.·Clin Transl Oncol
2025Cohort
Pan-cancer analysis of phagocytosis regulators in female-specific cancers: a focus on HMGB2.
Lu X et al.·Front Immunol
2025
[Immunological alterations in common variable immunodeficiency].
Berrón-Ruiz L·Rev Alerg Mex
2017Review
TGF-β-induced apoptosis of B-cell lymphoma Ramos cells through reduction of MS4A1/CD20.
Kawabata KC et al.·Oncogene
2013
Current status of antibody therapy in ALL.
Ai J et al.·Br J Haematol
2015Review
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