MUC4

Chr 3

mucin 4, cell surface associated

Also known as: ASGP, HSA276359, MUC-4

NCBI Gene: 4585ENSG00000145113UniProt: Q99102

This protein is a membrane-bound mucin that forms the major component of mucus covering epithelial surfaces and regulates epithelial cell proliferation and differentiation through interactions with ERBB2 receptor signaling. The gene is extremely tolerant to loss-of-function variants in the general population, and pathogenic variants have not been established to cause human disease. MUC4 contains highly variable tandem repeat regions that complicate genetic analysis and may contribute to its apparent tolerance to sequence variation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
102
Pubs (1 yr)
41
P/LP submissions
0%
P/LP missense
0.99
LOEUF
DN
Mechanism· predicted
Clinical Summary— MUC4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 18 VUS of 488 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.61
OE 0.84 (0.70–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-18.87Z-score
OE missense 2.03 (1.96–2.00)
5424 obs / 2676.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.84 (0.70–0.99)
0≤0.351.4
Missense OE2.03 (1.96–2.00)
0≤0.61.4
Synonymous OE1.76
0≤1.21.6
LoF obs/exp: 93 / 111.3Missense obs/exp: 5424 / 2676.2Syn Z: -20.51
DN
0.6260th %ile
GOF
0.3788th %ile
LOF
0.4528th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

488 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic1
VUS18
Likely Benign222
Benign14
40
Pathogenic
1
Likely Pathogenic
18
VUS
222
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
40
0
40
Likely Pathogenic
0
0
1
0
1
VUS
3
1
14
0
18
Likely Benign
2
58
13
149
222
Benign
2
7
2
3
14
Total76670152295

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

View in ClinVar →

Protein Context — Lollipop Plot

MUC4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Novel EPS15 :: KLF17 and EPS15L1 :: KLF17 Fusions Define a Distinctive Group of MUC4-Positive Spindled to Epithelioid Sarcomas.
Malik F et al.·Am J Surg Pathol
2026
APC-Mutated MUC4-Positive Fibroblastoma With Cytoplasmic β-Catenin: A Novel Variant Expanding Its Immunophenotypic Spectrum.
Onalaja-Underwood A et al.·Cureus
2026Open Access
Immunohistochemical Analysis of MUC1 and MUC4 Co-expression in Oral Leukoplakia and Oral Squamous Cell Carcinoma.
Abidullah M.·Ann Afr Med
2026
Correction: Althenayyan et al. Alternatively Spliced Isoforms of MUC4 and ADAM12 as Biomarkers for Colorectal Cancer Metastasis. J. Pers. Med. 2023, 13, 135.
Althenayyan S et al.·J Pers Med
2026Open Access
An update on the diagnostic and prognostic value of MUC4 expression in gastric cancers.
Aithal A et al.·Expert Rev Mol Diagn
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients