MUC1

Chr 1AD

mucin 1, cell surface associated

Also known as: ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3, EMA, H23AG

NCBI Gene: 4582ENSG00000185499OMIM: 158340

This gene encodes a membrane-bound protein that 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. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]

GeneReviewsOMIMResearchGenerating clinical summary…
MultiplemechanismADLOEUF 0.681 OMIM phenotype
Clinical Summary— MUC1
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Gene-Disease Validity (ClinGen)
tubulointerstitial kidney disease, autosomal dominant, 2 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
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ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 104 VUS of 161 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — MUC1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.68LOEUF
pLI 0.019
Z-score 2.54
OE 0.34 (0.19–0.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-1.23Z-score
OE missense 1.21 (1.11–1.33)
325 obs / 268.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.34 (0.19–0.68)
0≤0.351.4
Missense OE?1.21 (1.11–1.33)
0≤0.61.4
Synonymous OE?1.20
0≤1.21.6
LoF obs/exp: 6 / 17.4Missense obs/exp: 325 / 268.2Syn Z: -1.72

This gene — mechanism propensity

DN
0.85top 5%
GOF
0.94top 5%
LOF
0.2872th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

161 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic7
VUS104
Likely Benign25
Benign4
Conflicting2
3
Pathogenic
7
Likely Pathogenic
104
VUS
25
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
1
0
3
Likely Pathogenic
7
0
0
0
7
VUS
8
95
0
1
104
Likely Benign
0
13
0
12
25
Benign
0
0
2
2
4
Conflicting
—2
Total17108315145

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap MUC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

MUC1 · 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
Inflammatory Bowel DiseasesCrohn Disease

Predicting IBD Treatment Outcomes With Gut Microbiome Analysis

RECRUITING
NCT06453720University of British ColumbiaStarted 2024-08-01
Colonoscopy
Breast Cancer

Anti-Inflammatory Diet in BRC Patients on Aromatase Inhibitors

RECRUITING
NCT06214598Phase NAUniversity of BelgradeStarted 2024-03-01
SupplementAI dietPlacebo
Anaplastic Large Cell Lymphoma, ALK-NegativeAnaplastic Large Cell Lymphoma, ALK-PositiveApocrine Carcinoma

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

ACTIVE NOT RECRUITING
NCT02978625Phase PHASE2National Cancer Institute (NCI)Started 2017-09-27
Biopsy ProcedureBiospecimen CollectionComputed Tomography
Breast Cancer MetastaticBreast Carcinoma

Immun Checkpoint Washout in Patients With Invasive Ductal Breast Cancer

RECRUITING
NCT07003009Phase NAIstanbul Training and Research HospitalStarted 2024-01-01
Malign Lymph Node WashoutBenign Lymph Node Washout
Liver CancerLung CancerBreast Cancer

Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors

RECRUITING
NCT04842812Phase PHASE1Second Affiliated Hospital of Guangzhou Medical UniversityStarted 2021-01-01
TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3
CancerBreast CancerGastric Cancer

Predictive Value of Progastrin Titer at Diagnosis and of Progastrin Kinetics During Treatment in Cancer Patients

RECRUITING
NCT03787056Phase NAHospices Civils de LyonStarted 2018-12-04
Blood draws
Inflammatory Bowel Disease (IBD)

Personalized Exercise Coaching to Improve Quality of Life in Pediatric IBD

ACTIVE NOT RECRUITING
NCT07355101Phase NAUniversiteit AntwerpenStarted 2025-11-01
Intake session to define individualized physical activity goalsPersonalized Motivational Coaching24 Week Exercise Programme
Multiple Myeloma

A Clinical Study of TQB2029 for Injection in Subjects With Multiple Myeloma

RECRUITING
NCT06700395Phase PHASE1Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.Started 2024-11-28
TQB2029 injection
Acute Myeloid Leukemia

Multi-CAR T Cell Therapy for Acute Myeloid Leukemia

RECRUITING
NCT03222674Phase PHASE1, PHASE2Shenzhen Geno-Immune Medical InstituteStarted 2025-07-15
Muc1/CLL1/CD33/CD38/CD56/CD123-specific gene-engineered T cells
Malignant NeoplasmOrgan Damage

Construction and Evaluation of Tumor Immunotherapy and Organ Damage Early Warning System Based on Multi-omics

RECRUITING
NCT07131007Hebei Medical University Fourth HospitalStarted 2025-09-15
Immunotherapy Monitoring and Sample Collection
Sinusitis, ChronicSinus DiseaseSinus Infection

Microbiota Transfer for Chronic Rhinosinusitis

ACTIVE NOT RECRUITING
NCT05454072Phase NAAmin JaverStarted 2022-06-15
Sinonasal Microbiota TransferSham Sinonasal Microbiota Transfer
Type1diabetes

Crosstalk Between Mucosal-Associated Invariant T (MAIT) Cells and the Gut Microbiota and Mucosa in the Development of Type 1 Diabetes in Children

RECRUITING
NCT05054361Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2022-01-01
MAIT cells analysisMAIT cytokines production analysisLactulose/Mannitol Test

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