MUC16

Summary

MUC16 (mucin 16, cell surface associated, HGNC:15582) is a protein-coding gene on chromosome 19p13.2, encoding Mucin-16 (Q8WXI7). Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces.

This gene encodes a protein that is a member of the mucin family. Mucins are high molecular weight, O-glycosylated proteins that play an important role in forming a protective mucous barrier, and are found on the apical surfaces of the epithelia. The encoded protein is a membrane-tethered mucin that contains an extracellular domain at its amino terminus, a large tandem repeat domain, and a transmembrane domain with a short cytoplasmic domain. The amino terminus is highly glycosylated, while the repeat region contains 156 amino acid repeats unit that are rich in serines, threonines, and prolines. Interspersed within the repeats are Sea urchin sperm protein Enterokinase and Agrin (SEA) modules, leucine-rich repeats and ankyrin (ANK) repeats. These regions together form the ectodomain, and there is a potential cleavage site found near an SEA module close to the transmembrane domain. This protein is thought to play a role in forming a barrier, protecting epithelial cells from pathogens. Products of this gene have been used as a marker for different cancers, with higher expression levels associated with poorer outcomes.

Source: NCBI Gene 94025 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 700 total — 13 likely-pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes
• MANE Select transcript: NM_001401501

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15582
Approved symbol	MUC16
Name	mucin 16, cell surface associated
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	CA125, FLJ14303, CA-125
Ensembl gene	ENSG00000181143
Ensembl biotype	protein_coding
OMIM	606154
Entrez	94025

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000397910, ENST00000596768, ENST00000596956, ENST00000599436, ENST00000601404, ENST00000710609, ENST00000710610, ENST00000711672

RefSeq mRNA: 4 — MANE Select: NM_001401501 NM_001401501, NM_001414686, NM_001414687, NM_024690

CCDS: CCDS54212

Canonical transcript exons

ENST00000711671 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 97.66.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7659 / max 460.4618, expressed in 191 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178991	1.4988	177
178994	0.1875	8
178992	0.0509	19
178980	0.0166	5
178995	0.0122	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	97.66	gold quality
epithelium of bronchus	UBERON:0002031	96.69	gold quality
bronchus	UBERON:0002185	96.53	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.51	gold quality
bronchial epithelial cell	CL:0002328	96.31	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.08	gold quality
palpebral conjunctiva	UBERON:0001812	92.64	gold quality
trachea	UBERON:0003126	92.25	gold quality
epithelium of nasopharynx	UBERON:0001951	90.83	gold quality
right uterine tube	UBERON:0001302	88.66	gold quality
nasal cavity mucosa	UBERON:0001826	88.42	gold quality
minor salivary gland	UBERON:0001830	81.91	gold quality
omental fat pad	UBERON:0010414	77.59	gold quality
peritoneum	UBERON:0002358	77.53	gold quality
germinal epithelium of ovary	UBERON:0001304	77.02	gold quality
mouth mucosa	UBERON:0003729	76.47	gold quality
adipose tissue of abdominal region	UBERON:0007808	75.58	gold quality
saliva-secreting gland	UBERON:0001044	75.37	gold quality
endometrium	UBERON:0001295	75.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.30	gold quality
left uterine tube	UBERON:0001303	73.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.51	gold quality
fallopian tube	UBERON:0003889	71.03	gold quality
parietal pleura	UBERON:0002400	70.09	gold quality
pancreatic ductal cell	CL:0002079	66.49	silver quality
oviduct epithelium	UBERON:0004804	65.54	gold quality
decidua	UBERON:0002450	65.32	gold quality
sperm	CL:0000019	65.09	gold quality
male germ cell	CL:0000015	64.01	gold quality
pleura	UBERON:0000977	63.31	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	5228.51
E-GEOD-86618	yes	766.84
E-CURD-7	yes	309.73
E-CURD-114	yes	56.37
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• The CA 125 gene: a newly discovered extension of the glycosylated N-terminal domain doubles the size of this extracellular superstructure (PMID:12218296)
• ovarian carcinoma antigen CA125 may induce specific immunomodulatory effects by employing its carbohydrate sequences as functional groups, thereby promoting tumor progression (PMID:12734200)
• A correlation has been found between CA125 expression and prognosis in renal cell carcinoma patients who underwent nephrectomy. (PMID:12893366)
• might contribute to the metastasis of ovarian cancer to the peritoneum by initiating cell attachment to the mesothelial epithelium via binding to mesothelin (PMID:14676194)
• There was no significant difference between natural and stimulated cycles in concentrations of PP 14 and CA-125 in uterine flushings performed in the mid-luteal phase. (PMID:15016783)
• results showed the cell surface expression of CA125 in both adenocarcinoma and large cell carcinoma cell lines and the production of CA125 in culture medium (PMID:15599662)
• CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged (PMID:16174214)
• Eighty-six patients (43%) had elevated CA 125 levels and 35 (17.5%) had elevated mucin 1 levels at diagnosis (PMID:16194893)
• CA125 is expressed in patients with non-Hodgkin’s lymphoma but appears not to be secreted by lymphoma cells directly (PMID:16923563)
• With this in mind we can hypothesize that the development of ascites was the primary cause for the elevation of CA-125 in SLE patients with nephrotic syndrome rather than the nephrotic syndrome itself. (PMID:16979301)
• MUC16-Mesothelin binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors. (PMID:17067392)
• Results show that MUC16 is present in the whole lacrimal apparatus and its distribution pattern suggests different physiological functions with regard to tear film physiology and tear outflow. (PMID:17211626)
• This is th e first study to show that serum CA 125 is related to the presence and severity of heart failure and diastolic dysfunction in hypertrophic cardiomyopathy. (PMID:17285443)
• The most prominent delay in CA-125 decline was in patients given liposomal doxorubicin compared with those given topotecan or carboplatin. (PMID:17300679)
• The CA125 change after first course of inductiion chemotherapy was independent prognostic factors for both achievement of pathological complete response and overall survival. (PMID:17301071)
• Our results suggest that an immunohistochemical panel consisting of TTF-1, CEA, CA-125, and OCT-4 is helpful in distinguishing most pulmonary and ovarian carcinomas with clear cell features. (PMID:17413979)
• Overall survival was closely related with the 4-week CA125 tumor marker response. (PMID:17449138)
• This study shows that MUC1, MUC4, and MUC16 are regulated differently by dexamethasone in human corneal epithelial cells. (PMID:17592322)
• MUC16 is the major [(35)S]sulphate-labelled mucin in normal human bronchial epithelial cell secretions. (PMID:17604678)
• Both CA125 and brain natriuretic peptide (BNP) levels are significantly correlated with New York Heart Association (NYHA) class and outcome in patients with aortic stenosis. (PMID:17662495)
• A four-marker panel of CA-125, macrophage chemotactic protein-1, leptin, and macrophage migration inhibitory factor could diagnose the presence of endometriosis with 93% accuracy. (PMID:17706208)
• Measurement of CA 15-3 serum values in conjunction with sHER2 and CA 15-3 can increase sensitivity in metastasis detection. (PMID:17852076)
• Results show that measurements of AFP, CEA and CA125 are more readily affected by long-term frozen storage compared with frequent freezing-thawing. (PMID:17852813)
• These data indicate that MUC16 is a membrane component of the nonreceptive luminal uterine surface, which prevents cell adhesion, and that its removal during uterodome formation facilitates adhesion of the trophoblast. (PMID:17942799)
• The frequency of expression of Ca125…in invasive micropapillary carcinomas…was similar to the results in unselected mammary carcinoma. (PMID:18042071)
• In ovarian metastases from undiagnosed colorectal adenocarcinomas, elevated CA-125 levels and frequent coexpression of cytokeratin 7 are features that can contribute to misclassification of these metastases as primary ovarian neoplasms. (PMID:18317225)
• Expression and distribution of MUC16 in conjunctival and corneal epithelial cell lines is monitored by RTPCR and immunocytochemistry. (PMID:18342144)
• evaluate the usefulness of CA-125 normalized in time area under the curve (CA-125 AUC) to signalise epithelial ovarian cancer relapse (PMID:18503158)
• Neutrophil-to-lymphocyte ratio may be used as an adjunct to CA-125 for the diagnosis of endometriosis. (PMID:18555226)
• Serum CA-125 levels may serve as a useful predictor of pathological outcomes in patients undergoing cystectomy for urothelial carcinoma of the bladder (PMID:18555706)
• Serum samples were investigated for carcinoembryonic antigen (CEA), CA125 and MUC1, alpha-foetoprotein, neuron-specific enolase and CA19.9. (PMID:18609108)
• Changes in conjunctival epithelial MUC16 and MUC5AC mRNA expression is thought to be important in the pathogenesis of atopic ocular surface disease. (PMID:18782111)
• Women with intrauterine abortion hadsignificantly higher serum CA-125 and LDH levels compared to women with ectopic and normal intrauterine pregnancies;Ruptured tubal pregnancies resulted in significantly higher CA-125 (PMID:18797897)
• Risk of recurrence during follow-up for optimally treated advanced epithelial ovarian cancer with a low-level increase of serum CA125 levels is reported. (PMID:18820245)
• Reflux laryngitis is associated with down-regulation of mucin gene expression. (PMID:18834073)
• increased serum levels in a case of primary plasma cell leukemia (PMID:18854288)
• Serum CA125 was significantly higher in patients with ovarian cancer. (PMID:19060592)
• A binding domain on mesothelin for CA125/MUC16. (PMID:19075018)
• These results demonstrate that Sjogren’s syndrome subjects display a significant increase in both soluble MUC16 and MUC16 mRNA concentrations compared to other forms of aqueous deficient dry eye and non dry-eyed individuals. (PMID:19122828)
• Invasive micropapillary carcinoma more commonly showed immunoreactivity for MUC1, CA125, and Her2Neu compared to invasive urothelial carcinoma with retraction artifact (PMID:19270645)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Muc16	ENSMUSG00000109564
rattus_norvegicus		ENSRNOG00000072977

Protein

Protein identifiers

Mucin-16 — Q8WXI7 (reviewed: Q8WXI7)

Alternative names: Ovarian cancer-related tumor marker CA125, Ovarian carcinoma antigen CA125

All UniProt accessions (7): A0AA34QVW0, A0AA34QW05, A0AAA9YHI4, Q8WXI7, M0QZZ9, M0R2S7, M0R2Y5

UniProt curated annotations — full annotation on UniProt →

Function. Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces.

Subunit / interactions. Binds to MSLN. Binding to MSLN mediates heterotypic cell adhesion. This may contribute to the metastasis of ovarian cancer to the peritoneum by initiating cell attachment to the mesothelial epithelium via binding to MSLN.

Subcellular location. Cell membrane. Secreted. Extracellular space.

Tissue specificity. Expressed in corneal and conjunctival epithelia (at protein level). Overexpressed in ovarian carcinomas and ovarian low malignant potential (LMP) tumors as compared to the expression in normal ovarian tissue and ovarian adenomas.

Post-translational modifications. Heavily O-glycosylated; expresses both type 1 and type 2 core glycans. Heavily N-glycosylated; expresses primarily high mannose and complex bisecting type N-linked glycans. May be phosphorylated. Phosphorylation of the intracellular C-terminal domain may induce proteolytic cleavage and the liberation of the extracellular domain into the extracellular space. May contain numerous disulfide bridges. Association of several molecules of the secreted form may occur through interchain disulfide bridges providing an extraordinarily large gel-like matrix in the extracellular space or in the lumen of secretory ducts.

Domain organisation. Composed of three domains, a Ser-, Thr-rich N-terminal domain, a repeated domain containing between 12 and 60 partially conserved tandem repeats of 156 amino acids and a C-terminal transmembrane contain domain with a short cytoplasmic tail.

Induction. Up-regulated in ovarian cancer cells.

Polymorphism. The number of repeats is highly polymorphic and can be composed between 12 and 60 extracellular mucin repeats.

Miscellaneous. Antigen that is the basis for a widely used serum assay for the monitoring of patients with ovarian epithelial cancer. Due to lack of sensitivity for stage I disease and lack of specificity, it is of little value in the detection of early ovarian cancer. Due to its similarly elevated levels in some nonmalignant conditions, it is not specific enough to be used for population screening.

RefSeq proteins (4): NP_001388430, NP_001401615, NP_001401616, NP_078966 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000082	SEA_dom	Domain
IPR028850	MUC16	Family
IPR036364	SEA_dom_sf	Homologous_superfamily

Pfam: PF01390

UniProt features (535 total): compositionally biased region 151, region of interest 112, glycosylation site 102, sequence conflict 80, sequence variant 25, domain 16, disulfide bond 14, repeat 12, helix 10, strand 7, topological domain 2, turn 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7SA9	X-RAY DIFFRACTION	1.69
8VRS	X-RAY DIFFRACTION	2.47
8GKL	X-RAY DIFFRACTION	2.6
8VM1	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

No AlphaFold model available for Q8WXI7 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Antibody-complex structures (SAbDab): 2 — 8GKL, 8VRS

Functional residue map

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

Disulfide bonds (14): 12126–12146, 12282–12302, 12440–12460, 12596–12616, 12751–12771, 12907–12927, 13063–13083, 13219–13239, 13375–13395, 13531–13551, 13687–13707, 13976–13996, 14126–14146, 14373–14393

Glycosylation sites (102): 139, 434, 787, 930, 957, 1375, 1633, 1840, 1877, 1890, 2345, 2375, 2737, 3085, 3178, 3501, 4220, 4498, 4606, 4613 …

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: 86 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_CELL_SURFACE, MODULE_205, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOCC_SIDE_OF_MEMBRANE, SMID_BREAST_CANCER_LUMINAL_B_DN, GOCC_GOLGI_LUMEN, chr19p13, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, LIN_SILENCED_BY_TUMOR_MICROENVIRONMENT, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MARTENS_TRETINOIN_RESPONSE_UP

GO Biological Process (1): cell adhesion (GO:0007155)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): Golgi lumen (GO:0005796), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), vesicle (GO:0031982), extracellular exosome (GO:0070062), extracellular region (GO:0005576), membrane (GO:0016020)

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
cellular process	1
binding	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
membrane-bounded organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

1564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MUC16	MSLN	Q13421	994
MUC16	LGALS3	P17931	947
MUC16	MUC4	Q99102	930
MUC16	MUC1	P13931	897
MUC16	SIGLEC9	Q9Y336	885
MUC16	MUC17	Q685J3	854
MUC16	MUC12	Q9UKN1	845
MUC16	MUC3A	Q02505	839
MUC16	MUC13	Q9H3R2	819
MUC16	MUC5AC	P98088	818
MUC16	MUC15	Q8N387	813
MUC16	MUC6	Q6W4X9	785
MUC16	MUC2	Q02817	781
MUC16	CTNNB1	P35222	777
MUC16	LRP1B	Q9NZR2	774
MUC16	TTN	Q8WZ42	774

IntAct

3 interactions, top by confidence:

A	B	Type	Score
RAD21	PDS5B	psi-mi:“MI:0914”(association)	0.530
CEP170P1	PCYT1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): MUC16 (Affinity Capture-MS), MUC16 (Affinity Capture-MS), MUC16 (Affinity Capture-MS), MUC16 (Affinity Capture-MS), MUC16 (Affinity Capture-MS), MUC16 (Affinity Capture-MS), MUC16 (Affinity Capture-RNA), MUC16 (Affinity Capture-RNA), MUC16 (Affinity Capture-Western), MUC16 (Affinity Capture-MS), MUC16 (Proximity Label-MS), MUC16 (Proximity Label-MS), FYCO1 (Cross-Linking-MS (XL-MS)), GDAP2 (Cross-Linking-MS (XL-MS)), MUC16 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GUW6, A1EGX6, A6NM11, A6NMS7, A6QLF8, D3YU32, I3L273, J3KML8, O35930, O60309, Q08DY0, Q14242, Q2TBI7, Q32KG4, Q32L62, Q3MIW9, Q3TNW5, Q3V0E1, Q4R729, Q5VWK0, Q5VYM1, Q62170, Q659K0, Q68DN1, Q6AZ54, Q6MG22, Q6UXB8, Q6ZRG5, Q8BUE7, Q8K4E0, Q8N307, Q8N3K9, Q8TCU4, Q8WNU4, Q8WXI7, Q95JY5, Q96F05, Q96JA4, Q96M34, Q96M43

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	13
Uncertain significance	4
Likely benign	252
Benign	286

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
2584717	NM_001401501.2(MUC16):c.43669del (p.Ser14557fs)	Likely pathogenic
2584718	NM_001401501.2(MUC16):c.25861G>A (p.Glu8621Lys)	Likely pathogenic
2584720	NM_001401501.2(MUC16):c.23426C>T (p.Ser7809Phe)	Likely pathogenic
2584721	NM_001401501.2(MUC16):c.9849A>G (p.Glu3283=)	Likely pathogenic
2584722	NM_001401501.2(MUC16):c.4792C>A (p.Leu1598Ile)	Likely pathogenic
2584723	NM_001401501.2(MUC16):c.1098T>C (p.Ala366=)	Likely pathogenic
2584724	NM_001401501.2(MUC16):c.39435C>T (p.Cys13145=)	Likely pathogenic
2584725	NM_001401501.2(MUC16):c.39417_39418inv (p.Gly13140Arg)	Likely pathogenic
2584727	NM_001401501.2(MUC16):c.38195G>C (p.Ser12732Thr)	Likely pathogenic
2584728	NM_001401501.2(MUC16):c.33244G>A (p.Val11082Met)	Likely pathogenic
2584729	NM_001401501.2(MUC16):c.32216C>T (p.Pro10739Leu)	Likely pathogenic
2584730	NM_001401501.2(MUC16):c.26832T>G (p.Pro8944=)	Likely pathogenic
2584731	NM_001401501.2(MUC16):c.26738C>G (p.Ser8913Cys)	Likely pathogenic

SpliceAI

8717 predictions. Top by Δscore:

Variant	Effect	Δscore
19:8851265:T:TA	donor_gain	1.0000
19:8855970:TTACC:T	donor_loss	1.0000
19:8855971:TA:T	donor_loss	1.0000
19:8855973:C:A	donor_loss	1.0000
19:8856136:CAGAC:C	acceptor_gain	1.0000
19:8856138:GAC:G	acceptor_gain	1.0000
19:8858199:CTTA:C	donor_loss	1.0000
19:8858200:TTA:T	donor_loss	1.0000
19:8858201:TACC:T	donor_loss	1.0000
19:8858202:A:AC	donor_gain	1.0000
19:8858203:C:CA	donor_loss	1.0000
19:8858203:C:CC	donor_gain	1.0000
19:8858272:C:CC	acceptor_gain	1.0000
19:8858603:AT:A	donor_gain	1.0000
19:8858604:T:TA	donor_gain	1.0000
19:8858612:ATT:A	donor_gain	1.0000
19:8858614:T:TA	donor_gain	1.0000
19:8858623:T:TA	donor_gain	1.0000
19:8858747:CATTT:C	acceptor_gain	1.0000
19:8858749:TTT:T	acceptor_gain	1.0000
19:8858750:TT:T	acceptor_gain	1.0000
19:8858751:TCTA:T	acceptor_loss	1.0000
19:8858752:C:CC	acceptor_gain	1.0000
19:8858752:CTAG:C	acceptor_loss	1.0000
19:8858753:T:A	acceptor_loss	1.0000
19:8858758:T:C	acceptor_gain	1.0000
19:8860999:CCTG:C	donor_gain	1.0000
19:8861068:T:C	donor_gain	1.0000
19:8862871:A:AC	donor_gain	1.0000
19:8862872:C:CC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000007448 (19:8892537 G>T), RS1000017235 (19:8929936 G>T), RS1000042345 (19:8982567 T>A), RS1000053173 (19:8892795 G>A), RS1000085107 (19:8988440 G>A), RS1000088068 (19:8939708 T>C), RS1000090713 (19:8915647 G>A), RS1000090827 (19:8880156 C>A,T), RS1000117242 (19:8898107 CAG>C), RS1000123529 (19:8950986 G>A,T), RS1000130776 (19:8868385 C>T), RS1000140777 (19:8864320 C>T), RS1000199845 (19:8911985 C>A,T), RS1000227828 (19:8983247 C>G), RS1000265679 (19:9010320 G>A,T)

Disease associations

OMIM: gene MIM:606154 | disease phenotypes: MIM:167000, MIM:192500

GenCC curated gene-disease

Mondo (4): neutropenia (MONDO:0001475), lymphopenia (MONDO:0003783), ovarian cancer (MONDO:0008170), familial long QT syndrome (MONDO:0019171)

Orphanet (3): Rare ovarian cancer (Orphanet:213500), Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0001875	Decreased total neutrophil count
HP:0001888	Decreased total lymphocyte count

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003945_6	Hepcidin/transferrin saturation ratio	3.000000e-07
GCST007277_23	Tourette syndrome	4.000000e-07
GCST007798_109	Asthma	1.000000e-08
GCST009647_3	Serum cancer antigen 125 (CA 125) levels	2.000000e-17
GCST010042_138	Asthma	4.000000e-11
GCST010043_70	Asthma	1.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007902	hepcidin:transferrin saturation ratio
EFO:0010603	cancer antigen 125 measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008231	Lymphopenia	C15.378.243.750.605; C15.378.553.546.605; C20.673.627
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3580482 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11882256	Toxicity	3	opioids	Nausea;Vomiting

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11882256	MUC16	3	0.00	1	opioids

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
Cisplatin	decreases response to substance, affects cotreatment, decreases expression	2
Paclitaxel	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	increases expression	1
3,4-dichloroaniline	increases expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
necrostatin-1	decreases expression, decreases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
10-(6’-plastoquinonyl)decyltriphenylphosphonium	decreases expression, decreases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	increases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases expression	1
Boric Acids	decreases expression	1
Buserelin	affects cotreatment, increases expression	1
Caffeine	decreases phosphorylation	1
Diethylhexyl Phthalate	decreases expression	1
Diuron	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ozone	affects expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8L0	Abcam HCT 116 MUC16 KO	Cancer cell line	Male
CVCL_B8Z7	Abcam MCF-7 MUC16 KO	Cancer cell line	Female
CVCL_B9N7	Abcam A-549 MUC16 KO	Cancer cell line	Male
CVCL_D6AM	HyCyte A-549 KO-hMUC16	Cancer cell line	Male
CVCL_E0IH	Ubigene HeLa MUC16 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00125723	PHASE4	COMPLETED	FIRST - Study of Pegfilgrastim Administered in the First and Subsequent Cycles of Myelosuppressive Chemotherapy
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00257790	PHASE4	COMPLETED	The Tobramycin Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01114165	PHASE4	COMPLETED	Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
NCT01135589	PHASE4	UNKNOWN	Micafungin Prevention Study for Fungal Disease in Child Receiving Allogenic Hematopoietic Stem Cell Transplantation
NCT01571518	PHASE4	UNKNOWN	Prevention of Neutropenia After Using G-CSF With TAC Chemotherapy
NCT02621905	PHASE4	COMPLETED	Steady-State Comparative Bioavailability Study in Prophylaxis Patients of Lozanoc® 50 mg With Sporanox® 100 mg
NCT02967341	PHASE4	UNKNOWN	Blood Draw Validation for Ciprofloxacin Pharmacokinetic Research in Pediatric Cancer Patients
NCT04009941	PHASE4	COMPLETED	Efficacy and Safety of 4.5mg PEG-rhG-CSF Per Cycle in Preventing Neutropenia After Intensive Chemotherapy for Breast Cancer
NCT04904614	PHASE4	COMPLETED	Letermovir Use in Heart Transplant Recipients
NCT05626530	PHASE4	RECRUITING	Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients
NCT06145321	PHASE4	ACTIVE_NOT_RECRUITING	Continuous Versus Bolus Administration of G-CSF in Children With Cancer
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer