MUC21

Chr 6

mucin 21, cell surface associated

Also known as: C6orf205, KMQK697, MUC-21

NCBI Gene: 394263ENSG00000204544UniProt: Q5SSG8

This gene encodes a large membrane-bound glycoprotein which is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. The encoded protein contains an N-terminal signal sequence, an extracellular mucin domain, a stem domain, a transmembrane domain, and a C-terminal cytoplasmic tail domain. The mucin domain contains O-glycosylation sites and is polymorphic with isoforms containing a variable number of nonidentical proline-, threonine-, and serine-rich tandem repeats of 15 amino acids each. The aberrent expression of this gene is associated with lung adenocarcinoma. [provided by RefSeq, May 2017]

162
ClinVar variants
6
Pathogenic / LP
0.08
pLI score
0
Active trials
Clinical Summary— MUC21
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.08) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 84 VUS of 162 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.
1.41LOEUF
pLI 0.080
Z-score 1.04
OE 0.46 (0.19–1.41)
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.
0.57Z-score
OE missense 0.90 (0.81–1.00)
253 obs / 279.7 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.0.46 (0.19–1.41)
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 (0.81–1.00)
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.1.11
0≤1.21.6
LoF obs/exp: 2 / 4.3Missense obs/exp: 253 / 279.7Syn Z: -0.94

ClinVar Variant Classifications

162 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic2
VUS84
Likely Benign71
Benign1
4
Pathogenic
2
Likely Pathogenic
84
VUS
71
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
2
0
2
VUS
0
79
5
0
84
Likely Benign
0
13
1
57
71
Benign
1
0
0
0
1
Total1921257162

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

View in ClinVar →

Protein Context — Lollipop Plot

MUC21 · 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
A CRISPR activation screen identifies MUC-21 as critical for resistance to NK and T cell-mediated cytotoxicity.
Lee DH et al.·J Exp Clin Cancer Res
2023
Mucin 21 in esophageal squamous epithelia and carcinomas: analysis with glycoform-specific monoclonal antibodies.
Tian Y et al.·Glycobiology
2012
Defining molecular signatures of the solid/pseudopapillary and pseudoglandular patterns in so-called "solid-tubulocystic intrahepatic cholangiocarcinoma vs. NIPBL::NACC1 fusion hepatic carcinoma".
Bajpai P et al.·Pathol Res Pract
2025
Mucin 21 is a key molecule involved in the incohesive growth pattern in lung adenocarcinoma.
Yoshimoto T et al.·Cancer Sci
2019Case report
Natural selection of immune and metabolic genes associated with health in two lowland Bolivian populations.
Lea AJ et al.·Proc Natl Acad Sci U S A
2023
Entamoeba gingivalis induces gingival cell death, collagen breakdown, and host immune response via VAMP8/-3-driven exocytosis pathways.
Rosenfeld L et al.·Infect Immun
2025
The underlying molecular mechanism and identification of transcription factor markers for laryngeal squamous cell carcinoma.
Mo BY et al.·Bioengineered
2021Functional
A dynamic mucin mRNA signature associates with COVID-19 disease presentation and severity.
Smet A et al.·JCI Insight
2021
Polymorphisms in microRNA binding sites of mucin genes as predictors of clinical outcome in colorectal cancer patients.
Vymetalkova V et al.·Carcinogenesis
2017Cohort
RSPO4 is a potential risk gene of stages III-IV, grade C periodontitis through effects on innate immune response and oral barrier integrity.
Chopra A et al.·J Clin Periodontol
2023
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