MUC12

Summary

MUC12 (mucin 12, cell surface associated, HGNC:7510) is a protein-coding gene on chromosome 7q22.1, encoding Mucin-12 (Q9UKN1). Involved in epithelial cell protection, adhesion modulation, and signaling.

This gene encodes an integral membrane glycoprotein 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 and have been implicated in epithelial renewal and differentiation. These glycoproteins also play a role in intracellular signaling. This protein is expressed on the apical membrane surface of epithelial cells that line the mucosal surfaces of many different tissues including the colon, pancreas, prostate, and uterus. The expression of this gene is downregulated in colorectal cancer tissue.

Source: NCBI Gene 10071 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 61 total — 1 pathogenic
• MANE Select transcript: NM_001164462

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7510
Approved symbol	MUC12
Name	mucin 12, cell surface associated
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205277
Ensembl biotype	protein_coding
OMIM	604609
Entrez	10071

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000305119, ENST00000379442, ENST00000467414, ENST00000473098, ENST00000474482, ENST00000536621, ENST00000895813

RefSeq mRNA: 1 — MANE Select: NM_001164462 NM_001164462

CCDS: CCDS55139

Canonical transcript exons

ENST00000536621 — 12 exons

Exon	Start	End
ENSE00001167374	101015615	101015691
ENSE00001167377	101013913	101014074
ENSE00001167381	101012980	101013142
ENSE00001167383	101012819	101012890
ENSE00001167384	101012296	101012447
ENSE00001167389	101009095	101009159
ENSE00001167397	101008634	101008761
ENSE00001167404	101006471	101006572
ENSE00002260277	100990631	101005519
ENSE00003657657	101017575	101017663
ENSE00003675713	101018595	101018936
ENSE00003918676	100969565	100969689

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 98.96.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1153 / max 60.5127, expressed in 500 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80099	0.9695	455
80098	0.1458	75

Top tissues by expression

255 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	98.96	gold quality
mucosa of transverse colon	UBERON:0004991	98.59	gold quality
colonic mucosa	UBERON:0000317	98.42	gold quality
rectum	UBERON:0001052	97.86	gold quality
tendon of biceps brachii	UBERON:0008188	95.98	gold quality
ileal mucosa	UBERON:0000331	93.48	gold quality
transverse colon	UBERON:0001157	92.15	gold quality
colonic epithelium	UBERON:0000397	90.28	gold quality
large intestine	UBERON:0000059	85.26	gold quality
colon	UBERON:0001155	84.88	gold quality
intestine	UBERON:0000160	82.15	gold quality
oocyte	CL:0000023	78.89	silver quality
hypothalamus	UBERON:0001898	78.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.59	gold quality
prostate gland	UBERON:0002367	77.17	gold quality
anterior cingulate cortex	UBERON:0009835	77.17	gold quality
smooth muscle tissue	UBERON:0001135	76.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.70	gold quality
small intestine	UBERON:0002108	75.05	gold quality
right frontal lobe	UBERON:0002810	74.69	gold quality
ventricular zone	UBERON:0003053	74.61	gold quality
vermiform appendix	UBERON:0001154	74.58	gold quality
amygdala	UBERON:0001876	73.78	gold quality
muscle layer of sigmoid colon	UBERON:0035805	73.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	72.37	gold quality
caecum	UBERON:0001153	72.12	gold quality
stromal cell of endometrium	CL:0002255	70.41	gold quality
secondary oocyte	CL:0000655	67.80	gold quality
endocervix	UBERON:0000458	66.91	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	3021.63
E-GEOD-125970	yes	828.56
E-ANND-3	yes	19.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting MUC12, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Literature-anchored findings (GeneRIF, showing 6)

• Reflux laryngitis is associated with down-regulation of mucin gene expression. (PMID:18834073)
• Multivariate analysis disclosed that MUC12 expression status was an independent prognostic factor in Stages II and III CRC (relative risk, 8.236; 95% confidence interval, 1.702-39.849 p = 0.009). (PMID:20162577)
• Patients with active ulcerative colitis(UC) showed no significant expression of MUC12 gene in mucosa compared to the group of patients with UC in remission (PMID:26770020)
• Mucin12 is a protein that shows common antigenicity in both A. lumbricoides and its human host. (PMID:30481538)
• The oncogenic role of MUC12 in RCC progression depends on c-Jun/TGF-beta signalling. (PMID:32596961)
• piRNA-1742 promotes renal cell carcinoma malignancy by regulating USP8 stability through binding to hnRNPU and thereby inhibiting MUC12 ubiquitination. (PMID:37332045)

Cross-species orthologs

0 orthologs

Paralogs (1): SRRM2 (ENSG00000167978)

Protein

Protein identifiers

Mucin-12 — Q9UKN1 (reviewed: Q9UKN1)

Alternative names: Mucin-11

All UniProt accessions (2): Q9UKN1, H7BXN1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in epithelial cell protection, adhesion modulation, and signaling. May be involved in epithelial cell growth regulation. Stimulated by both cytokine TNF and TGF-beta in intestinal epithelium.

Subcellular location. Membrane.

Tissue specificity. Ubiquitous, with higher expression in colon. Down-regulated in colorectal cancer as well as in the colon of patients with ulcerative colitis (UC) and Crohn’s disease (CD).

Domain organisation. The proteolytic cleavage occurs within the SEA domain. This domain is not interchangeable, suggesting that it is insufficient to mediate efficient cleavage.

Induction. By listeriolysin O.

Miscellaneous. Infection by L.monocytogenes induces increases in mucin secretion and MUC4 and MUC12 transcription. This may constitute a host cell defense response that inhibits the entry of listeria monocytogenes in the cell.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UKN1-1	1	yes
Q9UKN1-2	2

RefSeq proteins (1): NP_001157934* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000082	SEA_dom	Domain
IPR000742	EGF	Domain
IPR036364	SEA_dom_sf	Homologous_superfamily
IPR052504	Mucin_signaling_protection	Family

Pfam: PF01390

UniProt features (218 total): compositionally biased region 146, repeat 28, glycosylation site 14, sequence conflict 12, region of interest 6, topological domain 2, domain 2, signal peptide 1, chain 1, site 1, disulfide bond 1, splice variant 1, sequence variant 1, transmembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q9UKN1 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 5229–5230 (cleavage)

Disulfide bonds (1): 5144–5153

Glycosylation sites (14): 154, 170, 176, 382, 738, 1793, 3350, 4433, 4571, 5169, 5182, 5197, 5228, 5264

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-5083625	Defective GALNT3 causes HFTC
R-HSA-5083632	Defective C1GALT1C1 causes TNPS
R-HSA-5083636	Defective GALNT12 causes CRCS1
R-HSA-5621480	Dectin-2 family
R-HSA-913709	O-linked glycosylation of mucins
R-HSA-977068	Termination of O-glycan biosynthesis
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-3781865	Diseases of glycosylation
R-HSA-3906995	Diseases associated with O-glycosylation of proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-5621481	C-type lectin receptors (CLRs)
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 31 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_GROWTH, GOBP_CELL_GROWTH, GOBP_REGULATION_OF_GROWTH, GOCC_GOLGI_LUMEN, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, REACTOME_DISEASES_OF_GLYCOSYLATION, REACTOME_DISEASES_ASSOCIATED_WITH_O_GLYCOSYLATION_OF_PROTEINS, REACTOME_DEFECTIVE_GALNT3_CAUSES_HFTC, REACTOME_DEFECTIVE_C1GALT1C1_CAUSES_TNPS, REACTOME_O_LINKED_GLYCOSYLATION, REACTOME_DECTIN_2_FAMILY, REACTOME_C_TYPE_LECTIN_RECEPTORS_CLRS, REACTOME_DISEASES_OF_METABOLISM, SUPT16H_TARGET_GENES

GO Biological Process (1): regulation of cell growth (GO:0001558)

GO Molecular Function (0):

GO Cellular Component (4): Golgi lumen (GO:0005796), plasma membrane (GO:0005886), membrane (GO:0016020), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	3
C-type lectin receptors (CLRs)	1
O-linked glycosylation	1
O-linked glycosylation of mucins	1
Immune System	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Innate Immune System	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1053 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MUC12	MUC13	Q9H3R2	960
MUC12	MUC15	Q8N387	905
MUC12	MUC2	Q02817	885
MUC12	MUC20	Q8N307	881
MUC12	MUC1	P13931	869
MUC12	MUC5B	Q9HC84	860
MUC12	MUC17	Q685J3	849
MUC12	MUC16	Q8WXI7	845
MUC12	MUC5AC	P98088	843
MUC12	MUC7	Q8TAX7	797
MUC12	MUC6	Q6W4X9	791
MUC12	MUC19	Q7Z5P9	776
MUC12	MUC21	Q5SSG8	774
MUC12	MUC22	E2RYF6	737
MUC12	MUC4	Q99102	657

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MUC12	RPL36	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350
CDC42	MUC12	psi-mi:“MI:0915”(physical association)	0.000
MUC12	MAPK14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): RPL36 (Proximity Label-MS), MUC12 (Negative Genetic), MUC12 (Negative Genetic), MUC12 (Affinity Capture-Western), MUC12 (Affinity Capture-MS), MUC12 (Two-hybrid), MUC12 (Two-hybrid)

ESM2 similar proteins: A0A0J9YWL9, A0A0J9YY54, A0A0U1RQI7, A0A494C071, A6NNC1, A6QL64, B3KS81, D3YZV8, E2RYF7, E9Q6E9, F1LWT0, F8W0I5, O60732, P0C8Z4, P0DKJ7, P0DKJ8, P0DKL2, P0DPF3, P18751, P20930, P43537, P53353, P59797, P62521, Q01456, Q08AG5, Q12816, Q3BBV2, Q5H9R4, Q5HY64, Q5JPF3, Q6P902, Q6ZQX7, Q86T75, Q86VE3, Q86VQ3, Q8BGJ3, Q8N307, Q8N7U7, Q8N7X1

Diamond homologs: Q685J3, Q9UKN1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MUC12	“up-regulates activity”	JUN	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

61 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	0
Likely benign	51
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3062968	GRCh37/hg19 7q22.1(chr7:100454649-101886704)x1	Pathogenic

SpliceAI

1540 predictions. Top by Δscore:

Variant	Effect	Δscore
7:101006525:GC:G	donor_gain	1.0000
7:101008631:CA:C	acceptor_loss	1.0000
7:101008759:CGGG:C	donor_loss	1.0000
7:101008760:GG:G	donor_gain	1.0000
7:101008760:GGGTA:G	donor_loss	1.0000
7:101008761:GG:G	donor_gain	1.0000
7:101008761:GGT:G	donor_loss	1.0000
7:101008762:G:GG	donor_gain	1.0000
7:101008763:T:A	donor_loss	1.0000
7:101009092:CAG:C	acceptor_loss	1.0000
7:101009093:A:AG	acceptor_gain	1.0000
7:101009093:AG:A	acceptor_loss	1.0000
7:101009093:AGAT:A	acceptor_gain	1.0000
7:101009093:AGATG:A	acceptor_gain	1.0000
7:101009094:G:GG	acceptor_gain	1.0000
7:101009094:GAT:G	acceptor_gain	1.0000
7:101009094:GATG:G	acceptor_gain	1.0000
7:101009094:GATGG:G	acceptor_gain	1.0000
7:101009155:TTGCT:T	donor_gain	1.0000
7:101009157:GCT:G	donor_gain	1.0000
7:101009157:GCTGT:G	donor_loss	1.0000
7:101009159:TGTG:T	donor_loss	1.0000
7:101009160:G:GG	donor_gain	1.0000
7:101009160:GT:G	donor_loss	1.0000
7:101009161:T:A	donor_loss	1.0000
7:101009162:GAGTA:G	donor_loss	1.0000
7:101012294:A:AG	acceptor_gain	1.0000
7:101012295:G:GA	acceptor_gain	1.0000
7:101012295:GCAAC:G	acceptor_gain	1.0000
7:101012445:G:GT	donor_gain	1.0000

AlphaMissense

33935 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:101008751:T:C	F5202S	0.998
7:101008751:T:G	F5202C	0.998
7:101012830:T:A	C5282S	0.998
7:101012831:G:C	C5282S	0.998
7:101008693:T:C	F5183L	0.997
7:101008695:C:A	F5183L	0.997
7:101008695:C:G	F5183L	0.997
7:101008739:T:G	F5198C	0.997
7:101012313:T:A	V5233D	0.997
7:101012331:T:C	L5239P	0.997
7:101012830:T:C	C5282R	0.997
7:101012985:T:A	C5304S	0.997
7:101012986:G:C	C5304S	0.997
7:101013096:T:A	C5341S	0.997
7:101013097:G:C	C5341S	0.997
7:101008694:T:G	F5183C	0.996
7:101008739:T:C	F5198S	0.996
7:101008750:T:C	F5202L	0.996
7:101008752:C:A	F5202L	0.996
7:101008752:C:G	F5202L	0.996
7:101013066:T:A	C5331S	0.996
7:101013067:G:C	C5331S	0.996
7:101013105:G:T	G5344C	0.996
7:101013111:T:A	C5346S	0.996
7:101013112:G:C	C5346S	0.996
7:101013138:T:A	C5355S	0.996
7:101013139:G:C	C5355S	0.996
7:101013953:T:A	C5370S	0.996
7:101013954:G:A	C5370Y	0.996
7:101013954:G:C	C5370S	0.996

dbSNP variants (sampled 300 via entrez): RS1000056282 (7:101018863 G>GGCACCCCT), RS1000114300 (7:101005087 A>C), RS1000210596 (7:100981991 G>A,C), RS1000233306 (7:100969439 G>A), RS1000260461 (7:100992583 T>A,G), RS1000272291 (7:100986970 T>C), RS1000296258 (7:100975671 G>A,T), RS1000392483 (7:100988068 G>A,C), RS1000420873 (7:100981560 T>C), RS1000440580 (7:101007424 T>A), RS1000475547 (7:100981843 C>T), RS1000521137 (7:100970866 G>A), RS1000594386 (7:100973988 TA>T,TAA), RS1000814423 (7:100980445 A>C,G), RS1000833834 (7:101011558 A>T)

Disease associations

OMIM: gene MIM:604609 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007096_237	Pulse pressure	4.000000e-10
GCST007250_7	Nonunion in individuals with fractures	3.000000e-07
GCST010083_107	Hemoglobin levels	1.000000e-19
GCST012431_6	Parkinson’s disease	3.000000e-18
GCST90014033_82	Haemorrhoidal disease	1.000000e-22

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0009707	fractures, ununited
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation	2
benzo(e)pyrene	increases methylation	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1
Cadmium	decreases expression	1
Bucladesine	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Malathion	decreases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Medroxyprogesterone Acetate	affects cotreatment, decreases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.