MUC1

mucin 1, cell surface associated, the group of CD molecules|Mucins

Basic information

Region (hg38): 1:155185824-155192916

Previous symbols: [ "PUM", "MCKD1" ]

Links

ENSG00000185499 ∙ NCBI:4582 ∙ OMIM:158340 ∙ HGNC:7508 ∙ Uniprot:P15941 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• tubulointerstitial kidney disease, autosomal dominant, 2 (Limited), mode of inheritance: Unknown
• tubulointerstitial kidney disease, autosomal dominant, 2 (Moderate), mode of inheritance: AD
• tubulointerstitial kidney disease, autosomal dominant, 2 (Supportive), mode of inheritance: AD
• tubulointerstitial kidney disease, autosomal dominant, 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tubulointerstitial kidney disease, autosomal dominant, 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Renal	15384011; 23396133
Renal transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MUC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MUC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			2	3		5
nonsense			2			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	4	4	0

Variants in MUC1

This is a list of pathogenic ClinVar variants found in the MUC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-155186146-C-G		Inborn genetic diseases	Uncertain significance (Aug 20, 2024)
1-155186148-G-C		Inborn genetic diseases	Uncertain significance (Jun 03, 2022)
1-155186157-G-C		MUC1-related disorder	Uncertain significance (Nov 22, 2023)
1-155186160-A-G		Inborn genetic diseases	Uncertain significance (Nov 13, 2023)
1-155186210-C-T		Tubulointerstitial kidney disease, autosomal dominant, 2	Likely pathogenic (Mar 26, 2024)
1-155187242-G-C		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
1-155187254-TA-T		Tubulointerstitial kidney disease, autosomal dominant, 2	Uncertain significance (Apr 04, 2024)
1-155187269-G-A		Inborn genetic diseases	Uncertain significance (Aug 26, 2022)
1-155187322-G-C		Tubulointerstitial kidney disease, autosomal dominant, 2	Uncertain significance (Jul 21, 2020)
1-155187344-C-T		MUC1-related disorder	Uncertain significance (Oct 28, 2023)
1-155187358-C-T		Inborn genetic diseases	Uncertain significance (May 26, 2023)
1-155187364-TGACA-T		Tubulointerstitial kidney disease, autosomal dominant, 2	Uncertain significance (Jul 30, 2021)
1-155187466-G-A		Inborn genetic diseases	Likely benign (Jun 23, 2021)
1-155187472-C-T		Inborn genetic diseases	Likely benign (Jun 29, 2023)
1-155187479-C-A		Inborn genetic diseases	Likely benign (Apr 04, 2024)
1-155187482-C-T		Inborn genetic diseases	Likely benign (May 20, 2024)
1-155187489-A-G			Uncertain significance (Dec 06, 2022)
1-155187499-C-T		Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
1-155187500-C-T		MUC1-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 27, 2025)
1-155187515-G-A		Tubulointerstitial kidney disease, autosomal dominant, 2 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 04, 2024)
1-155187525-C-T		Inborn genetic diseases	Uncertain significance (Jun 11, 2024)
1-155187538-C-A		Inborn genetic diseases	Likely benign (Dec 31, 2023)
1-155187538-C-T		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
1-155187540-C-T		Inborn genetic diseases	Uncertain significance (Aug 01, 2024)
1-155187729-G-A		MUC1-related disorder	Likely benign (Mar 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MUC1	protein_coding	protein_coding	ENST00000368395	8	4408

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0188	0.977	125177	0	24	125201	0.0000958

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.23	325	268	1.21	0.0000153	3015
Missense in Polyphen		140	118.41	1.1824		1380
Synonymous	-1.72	144	120	1.20	0.00000813	1069
Loss of Function	2.54	6	17.4	0.344	9.86e-7	180

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.000185	0.000185
European (Non-Finnish)	0.0000800	0.0000797
Middle Eastern	0.000435	0.000435
South Asian	0.00	0.00
Other	0.000164	0.000164

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.
• Disease: DISEASE: Note=MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes. {ECO:0000269|PubMed:20816948}.; DISEASE: Medullary cystic kidney disease 1 (MCKD1) [MIM:174000]: A form of tubulointerstitial nephropathy characterized by formation of renal cysts at the corticomedullary junction. It is characterized by adult onset of impaired renal function and salt wasting resulting in end-stage renal failure by the sixth decade. {ECO:0000269|PubMed:23396133}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Interleukin-4 and 13 signaling;Post-translational protein modification;Dectin-2 family;Metabolism of proteins;C-type lectin receptors (CLRs);TCR;Innate Immune System;Immune System;Fibroblast growth factor-1;Termination of O-glycan biosynthesis;O-linked glycosylation of mucins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.0717

Haploinsufficiency Scores

• pHI: 0.0248
• hipred: N
• hipred_score: 0.485
• ghis: 0.388

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.545

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Muc1
• Phenotype: digestive/alimentary phenotype; neoplasm; normal phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: stimulatory C-type lectin receptor signaling pathway;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator;negative regulation of transcription by competitive promoter binding;O-glycan processing;cytokine-mediated signaling pathway;negative regulation of cell adhesion mediated by integrin;positive regulation of transcription from RNA polymerase II promoter in response to stress;regulation of transcription from RNA polymerase II promoter in response to stress;positive regulation of histone H4 acetylation;negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
• Cellular component: nuclear chromatin;extracellular space;Golgi lumen;plasma membrane;integral component of plasma membrane;apical plasma membrane;vesicle;extracellular exosome
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;p53 binding;transcription coregulator activity;protein binding