CEACAM6

Summary

CEACAM6 (CEA cell adhesion molecule 6, HGNC:1818) is a protein-coding gene on chromosome 19q13.2, encoding Cell adhesion molecule CEACAM6 (P40199). Cell surface glycoprotein that plays a role in cell adhesion and tumor progression.

This gene encodes a protein that belongs to the carcinoembryonic antigen (CEA) family whose members are glycosyl phosphatidyl inositol (GPI) anchored cell surface glycoproteins. Members of this family play a role in cell adhesion and are widely used as tumor markers in serum immunoassay determinations of carcinoma. This gene affects the sensitivity of tumor cells to adenovirus infection. The protein encoded by this gene acts as a receptor for adherent-invasive E. coli adhesion to the surface of ileal epithelial cells in patients with Crohn’s disease. This gene is clustered with genes and pseudogenes of the cell adhesion molecules subgroup of the CEA family on chromosome 19.

Source: NCBI Gene 4680 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cystic fibrosis (Supportive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 52 total
• Phenotypes (HPO): 35
• MANE Select transcript: NM_002483

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1818
Approved symbol	CEACAM6
Name	CEA cell adhesion molecule 6
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CD66c, NCA-50/90
Ensembl gene	ENSG00000086548
Ensembl biotype	protein_coding
OMIM	163980
Entrez	4680

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000199764, ENST00000595740, ENST00000890871, ENST00000943164

RefSeq mRNA: 1 — MANE Select: NM_002483 NM_002483

CCDS: CCDS12585

Canonical transcript exons

ENST00000199764 — 6 exons

Exon	Start	End
ENSE00000842495	41766183	41766299
ENSE00001053047	41770802	41772211
ENSE00001806789	41755530	41755702
ENSE00002438901	41756600	41756959
ENSE00002477928	41761969	41762223
ENSE00002506588	41761249	41761527

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 99.94.

FANTOM5 (CAGE): breadth broad, TPM avg 7.6087 / max 1657.3322, expressed in 480 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176057	7.0306	472
176058	0.3670	82
176059	0.1817	49
176056	0.0293	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.94	gold quality
palpebral conjunctiva	UBERON:0001812	99.87	gold quality
nasal cavity epithelium	UBERON:0005384	99.57	gold quality
colonic mucosa	UBERON:0000317	99.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.38	gold quality
esophagus squamous epithelium	UBERON:0006920	99.36	gold quality
lower lobe of lung	UBERON:0008949	99.36	gold quality
pharyngeal mucosa	UBERON:0000355	99.26	gold quality
epithelium of bronchus	UBERON:0002031	99.20	gold quality
bronchial epithelial cell	CL:0002328	99.19	gold quality
bronchus	UBERON:0002185	99.19	gold quality
trabecular bone tissue	UBERON:0002483	99.19	gold quality
epithelium of nasopharynx	UBERON:0001951	99.15	gold quality
nasopharynx	UBERON:0001728	99.13	gold quality
tongue squamous epithelium	UBERON:0006919	99.08	gold quality
oral cavity	UBERON:0000167	99.02	gold quality
urethra	UBERON:0000057	98.85	gold quality
epithelium of esophagus	UBERON:0001976	98.73	gold quality
jejunal mucosa	UBERON:0000399	98.65	gold quality
rectum	UBERON:0001052	98.59	gold quality
right lung	UBERON:0002167	98.50	gold quality
trachea	UBERON:0003126	98.37	gold quality
cervix epithelium	UBERON:0004801	98.05	gold quality
body of tongue	UBERON:0011876	98.05	gold quality
lower esophagus mucosa	UBERON:0035834	98.03	gold quality
mucosa of transverse colon	UBERON:0004991	97.93	gold quality
cervix squamous epithelium	UBERON:0006922	97.79	gold quality
upper lobe of lung	UBERON:0008948	97.74	gold quality
upper lobe of left lung	UBERON:0008952	97.60	gold quality
visceral pleura	UBERON:0002401	97.48	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-86618	yes	6918.00
E-MTAB-9801	yes	2639.35
E-HCAD-15	yes	1916.79
E-MTAB-8530	yes	1894.19
E-MTAB-6653	yes	1209.55
E-MTAB-8410	yes	1037.31
E-CURD-114	yes	434.35
E-GEOD-125970	yes	26.83
E-HCAD-1	yes	22.52
E-GEOD-130148	yes	10.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, GLI2, TCF7

miRNA regulators (miRDB)

76 targeting CEACAM6, 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-4682	100.00	68.89	1258
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4446-5P	99.72	69.19	2544

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of CEACAM6 disrupts tissue architecture and blocks colonocyte differentiation (PMID:11896570)
• CEACAM6 subdomains involved in intercellular adhesion activity and subdomains involved in inhibition of cell differentation are identified and their respective activities are independently blocked. (PMID:12571231)
• the first study to demonstrate the prognostic relevance of CEACAM6 overexpression in human colorectal cancer (PMID:14512395)
• overexpression among human malignancies, immunological targeting of this tumor antigen may have therapeutic applicability (PMID:15081416)
• the results show that recognition of CEA and CEACAM6, but not CEACAM1, is accompanied by tight attachment to bacteria of cell surface microvilli-like extensions (PMID:15130118)
• CEACAM6 is an important determinant of pancreatic adenocarcinoma malignant cellular behavior (PMID:15208677)
• Levels of CEACAM6 expression can modulate pancreatic adenocarcinoma cellular invasiveness in a c-Src-dependent manner (PMID:15316565)
• CD66c is regulated in a manner distinct from other myeloid antigens in childhood lymphoblastic leukemia (PMID:15826304)
• Data show that variants of Neisseria gonorrhoeae that bind to human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) 1 and 6 failed to induce detachment and, instead, promoted enhanced host cell adhesion to the ECM. (PMID:16115956)
• The expression of CEACAM6 in ADH lesions is strongly associated with the development of IBC, therefore, it can be applied as a diagnostic marker either singly or in combination with other marker(s) to predict IBC development in women with ADH lesions. (PMID:16899629)
• CEA and CEACAM6 was shown to lead to an increase in the binding of the integrin alpha5beta1 receptor to its ligand fibronectin, without changing its cell surface levels, resulting in increased adhesion of CEA/CEACAM6-expressing cells to fibronectin. (PMID:17167768)
• For all tumors, the amount of CEACAM6 expressed was greater than that of CEACAM5, and reflected tumor histotype. (PMID:17201906)
• CEA-mediated signaling involves clustering of CEA and co-clustering and activation of the alpha5beta1 and associated specific signaling elements on the internal surfaces of membrane microdomains (PMID:17286276)
• CEACAM6 is a biological tumor marker for epithelial ovarian cancers. (PMID:17503391)
• CEACAM6 acts as a receptor for adherent-invasive E. coli adhesion and is abnormally expressed by ileal epithelial cells in Crohn disease. (PMID:17525800)
• findings suggest that CEA (CEACAM5) and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling. (PMID:17653079)
• All the leukemic samples showed overexpression of CEACAM6 and 8 when compared with normal granulocytes. (PMID:17909799)
• data support an important role for CEACAM6 in endocrine resistance in breast cancer, which can serve as a powerful predictor of future recurrence (PMID:18223215)
• CEACAM6 is overexpressed in borderline and invasive mucinous ovarian neoplasms. (PMID:18331757)
• Data show that desensitization of neutrophils to any two CEACAMs, 1, 3, 6, or 8, results in selective desensitization to those two CEACAMs, while the cells remain responsive to the other two neutrophil CEACAMs. (PMID:19077207)
• Because CEACAM6 acts as an antiapoptotic factor and stabilizes surfactant function, in addition to a putative role in innate defense against bacteria, we propose that it is a multifunctional alveolar protein (PMID:19329538)
• CEACAM6-associated signaling pathways could be potential targets for the development of biomarkers to predict the response of patients to adenovirus-based therapies, as well as for the development of more potent adenovirus-based therapeutics (PMID:19411761)
• CEACAM6 and a regulatory element near the 3’ end of CEACAM3 are associated with cystic fibrosis disease severity and intrapair discordance (PMID:20047061)
• Positivity for both leukemia-associated antigens CD66c and CD25 in combination can predict the presence of BCR/ABL rearrangement in pre-B cell acute lymphoblastic leukemia (PMID:20063526)
• The highly elevated gene expression of CEACAM6 and CEACAM8 in primary myelofibrosis can serve as molecular markers of myelofibrotic transformation. (PMID:21470677)
• Despite its important role in bacterial attachment in ileal CD, no role was detected for CEACAM6 variants in IBD susceptibility or regarding an ileal CD phenotype (PMID:21559399)
• High serum CEACAM6 is associated with gastric cancer. (PMID:21618249)
• High CEACAM6 expresssion is associated with inflammatory bowel disease. (PMID:21994005)
• CEACAM6 is expressed by alveolar and airway epithelial cells of human lung and is secreted into lung-lining fluid, where fully glycosylated protein binds to surfactant. (PMID:22037359)
• The authors show that the expression of CEACAM1 and CEACAM6 potentiate CEACAM3-dependent responses of neutrophils, exposing a cooperative role for this family of proteins during neisserial infection of neutrophils. (PMID:22064717)
• a novel role for NA in enhancing host cell survival by activating the Src/Akt signaling axis via an interaction with carcinoembryonic antigen-related cell adhesion molecule 6/cluster of differentiation 66c (C6). (PMID:22396546)
• CEACAM6 is significantly upregulated in colon cancer tissues and is closely associated with poor prognosis. (PMID:22975528)
• CEACAM6 is focally overexpressed in a large fraction of human HNSCCs in situ. over-expression of CEACAM6 increases tumour growth and tumour initiating activity by suppressing PI3K/AKT-dependent apoptosis of HNSCC in a xenotransplant model of HNSCC. (PMID:23021083)
• The expression of CD66c was significantly higher in colorectal cancer specimens than in normal colon. (PMID:23027178)
• these findings show that PDEF-CEACAM6 is a highly active oncogenic axis in breast cancer (PMID:23592399)
• CEACAM-6 plays an important role in the regulation of CD8+ T-cell responses against multiple myeloma. (PMID:23603913)
• High carcinoembryonic cell adhesion molecule 6 expression is associated with malignant biliary stenoses. (PMID:23806607)
• our findings identified CEACAM6, which is regulated by miR-29a/b/c, as an important positive regulator of EMT in pancreatic cancer (PMID:23857344)
• CD66c expression appears useful only as a predictor of the Ph in adult patients (not in pediatric cases). (PMID:24014076)
• CEACAM6 expression was expressed in different molecular subtypes of breast cancer. Among different subtypes, the highest expression was found with HER2 positive cancers. (PMID:24186057)

Cross-species orthologs

0 orthologs

Paralogs (24): CEACAM21 (ENSG00000007129), CEACAM7 (ENSG00000007306), CEACAM1 (ENSG00000079385), CEACAM4 (ENSG00000105352), CEACAM5 (ENSG00000105388), PSG8 (ENSG00000124467), CEACAM8 (ENSG00000124469), HEPACAM (ENSG00000165478), PSG6 (ENSG00000170848), CEACAM3 (ENSG00000170956), PSG9 (ENSG00000183668), CEACAM19 (ENSG00000186567), HEPACAM2 (ENSG00000188175), PSG5 (ENSG00000204941), CEACAM18 (ENSG00000213822), CEACAM16 (ENSG00000213892), VSTM5 (ENSG00000214376), PSG3 (ENSG00000221826), PSG7 (ENSG00000221878), PSG1 (ENSG00000231924), PSG2 (ENSG00000242221), PSG11 (ENSG00000243130), PSG4 (ENSG00000243137), CEACAM20 (ENSG00000273777)

Protein

Protein identifiers

Cell adhesion molecule CEACAM6 — P40199 (reviewed: P40199)

Alternative names: Carcinoembryonic antigen-related cell adhesion molecule 6, Non-specific crossreacting antigen, Normal cross-reacting antigen

All UniProt accessions (2): P40199, M0QYD3

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface glycoprotein that plays a role in cell adhesion and tumor progression. Intercellular adhesion occurs in a calcium- and fibronectin-independent manner. Mediates homophilic and heterophilic cell adhesion with other carcinoembryonic antigen-related cell adhesion molecules, such as CEACAM5 and CEACAM8. Heterophilic interaction with CEACAM8 occurs in activated neutrophils. Plays a role in neutrophil adhesion to cytokine-activated endothelial cells. Plays a role in cell migration and cell adhesion to endothelial cells.

Subunit / interactions. Homodimer; homodimerizes via its Ig-like V-type domain. Heterodimer with CEACAM8; heterodimerizes via its Ig-like V-type domain.

Subcellular location. Cell membrane. Apical cell membrane. Cell surface.

Tissue specificity. Expressed in neutrophils. Expressed in columnar epithelial and goblet cells of the colon. Expressed in numerous tumor cell lines (at protein level).

Post-translational modifications. Glycosylated.

Domain organisation. The extracellular N-terminus Ig-like V-type domain is necessary for homophilic and heterophilic intercellular adhesion.

Similarity. Belongs to the immunoglobulin superfamily. CEA family.

RefSeq proteins (1): NP_002474* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050831	CEA_cell_adhesion	Family

Pfam: PF07686, PF13895, PF13927

UniProt features (45 total): glycosylation site 12, mutagenesis site 10, strand 9, domain 3, disulfide bond 2, helix 2, signal peptide 1, chain 1, propeptide 1, sequence variant 1, sequence conflict 1, turn 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4Y8A	X-RAY DIFFRACTION	1.83
4YIQ	X-RAY DIFFRACTION	1.85
4WTZ	X-RAY DIFFRACTION	2.52
4WHC	X-RAY DIFFRACTION	2.71
9RCU	X-RAY DIFFRACTION	2.99
9RCS	X-RAY DIFFRACTION	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40199-F1	88.52	0.83

Functional residue map

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

Post-translational modifications (1): 320

Disulfide bonds (2): 167–215, 259–299

Glycosylation sites (12): 152, 173, 197, 224, 256, 274, 288, 292, 309, 104, 111, 115

Mutagenesis-validated functional residues (10):

Position	Phenotype
38	loss of homodimerization and heterodimerization with ceacam8.
53	no effect on homodimerization. reduces heterodimerization with ceacam8.
55	no effect on homophilic and heterophilic cell adhesion.
61	inhibits homophilic and heterophilic cell adhesion.
62	no effect on homophilic cell adhesion. reduces heterophilic cell adhesion.
63	no effect on homophilic cell adhesion. inhibits heterophilic cell adhesion.
66	inhibits homophilic cell adhesion. reduces heterophilic cell adhesion.
78	inhibits homophilic cell adhesion. no effect on heterophilic cell adhesion.
123	no effect on homodimerization. reduces heterodimerization with ceacam8.
129	reduces homodimerization. loss of heterodimerization with ceacam8.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1566977	Fibronectin matrix formation
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-6798695	Neutrophil degranulation
R-HSA-109582	Hemostasis
R-HSA-1474244	Extracellular matrix organization
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 282 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, MODULE_92, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_HETEROTYPIC_CELL_CELL_ADHESION, GOZGIT_ESR1_TARGETS_DN, GOCC_CELL_SURFACE, CROONQUIST_NRAS_SIGNALING_UP, ONDER_CDH1_TARGETS_3_DN, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POSITIVE_REGULATION_OF_CELL_MATRIX_ADHESION

GO Biological Process (9): apoptotic process (GO:0006915), homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), positive regulation of cell population proliferation (GO:0008284), positive regulation of cell migration (GO:0030335), positive regulation of heterotypic cell-cell adhesion (GO:0034116), positive regulation of endothelial cell-matrix adhesion (GO:1904906), negative regulation of anoikis (GO:2000811), cell adhesion (GO:0007155)

GO Molecular Function (3): identical protein binding (GO:0042802), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), apical plasma membrane (GO:0016324), azurophil granule membrane (GO:0035577), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Extracellular matrix organization	1
Hemostasis	1
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell-cell adhesion	2
membrane	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
positive regulation of cell-cell adhesion	1
heterotypic cell-cell adhesion	1
regulation of heterotypic cell-cell adhesion	1
positive regulation of cell-matrix adhesion	1
endothelial cell-matrix adhesion	1
regulation of endothelial cell-matrix adhesion	1
negative regulation of apoptotic process	1
anoikis	1
regulation of anoikis	1
cellular process	1
protein binding	1
protein dimerization activity	1
binding	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
lysosomal membrane	1
secretory granule membrane	1
azurophil granule	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEACAM6	CEACAM1	P13688	723
CEACAM6	CD74	P04233	605
CEACAM6	CDH1	P12830	559
CEACAM6	CEACAM8	P31997	554
CEACAM6	A1BG	P04217	551
CEACAM6	FN1	P02751	532
CEACAM6	MUC4	Q99102	529
CEACAM6	CD55	P08174	524
CEACAM6	TACSTD2	P09758	507
CEACAM6	MUC13	Q9H3R2	484
CEACAM6	DEFA4	P12838	478
CEACAM6	HCK	P08631	476
CEACAM6	MUC5B	Q9HC84	470
CEACAM6	MUC5AC	P98088	468
CEACAM6	MUC17	Q685J3	449

IntAct

106 interactions, top by confidence:

A	B	Type	Score
CEACAM6	CEACAM6	psi-mi:“MI:0915”(physical association)	0.840
CEACAM6	CEACAM6	psi-mi:“MI:0407”(direct interaction)	0.840
CEACAM6	CEACAM8	psi-mi:“MI:0407”(direct interaction)	0.820
CEACAM8	CEACAM6	psi-mi:“MI:0407”(direct interaction)	0.820
CEACAM8	CEACAM6	psi-mi:“MI:0915”(physical association)	0.820
CEACAM1	CEACAM6	psi-mi:“MI:0915”(physical association)	0.610
CEACAM6	CEACAM1	psi-mi:“MI:0407”(direct interaction)	0.610
CEACAM6	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
CEACAM6	ASPG	psi-mi:“MI:0915”(physical association)	0.560
GPANK1	CEACAM6	psi-mi:“MI:0915”(physical association)	0.560
TLX3	CEACAM6	psi-mi:“MI:0915”(physical association)	0.560
TNXB	CEACAM6	psi-mi:“MI:0915”(physical association)	0.560
CEACAM6	POM121	psi-mi:“MI:0915”(physical association)	0.560
CEACAM6	RHOXF2	psi-mi:“MI:0915”(physical association)	0.560
CEACAM6	ZMYND19	psi-mi:“MI:0915”(physical association)	0.560
CEACAM6	MYOZ1	psi-mi:“MI:0915”(physical association)	0.560
CEACAM6	SHC3	psi-mi:“MI:0915”(physical association)	0.560
CEACAM6	MSS51	psi-mi:“MI:0915”(physical association)	0.560
CEACAM6	PITX1	psi-mi:“MI:0915”(physical association)	0.560
ZNF76	CEACAM6	psi-mi:“MI:0915”(physical association)	0.560
VENTX	CEACAM6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (269): CEACAM6 (Affinity Capture-MS), CEACAM6 (Two-hybrid), CEACAM6 (Two-hybrid), CEACAM6 (Two-hybrid), CEACAM6 (Two-hybrid), CSTF2 (Two-hybrid), HPCAL4 (Two-hybrid), GCM2 (Two-hybrid), RHOXF2 (Two-hybrid), VEZF1 (Two-hybrid), SHC3 (Two-hybrid), VENTX (Two-hybrid), FOXH1 (Two-hybrid), TLX3 (Two-hybrid), ZMYND19 (Two-hybrid)

ESM2 similar proteins: A0A0K2S4Q6, A6NI73, O75019, O75022, O75023, O76036, P0C191, P11464, P11465, P13688, P31997, P40199, P59901, Q00887, Q00888, Q00889, Q08708, Q0V881, Q15238, Q16557, Q28110, Q496F6, Q5M7U7, Q5SQ64, Q6GTX8, Q6ISS4, Q6MG56, Q6PI73, Q863H2, Q863H3, Q8C567, Q8IYS5, Q8MHY9, Q8MJZ2, Q8N149, Q8N423, Q8N6C8, Q8VBT3, Q95JB9, Q96LA5

Diamond homologs: A0A0B4J1L0, D3ZQE1, E9QA28, O75871, P06731, P11464, P11465, P13688, P16573, P31809, P31997, P40198, P40199, Q00887, Q00888, Q00889, Q13046, Q14002, Q15238, Q16557, Q2WEN9, Q3KPI0, Q3UKK2, Q61400, Q63111, Q810J1, Q925P2, Q9D2Z1, Q9UQ72, Q9UQ74, Q0E9H9, Q6UY09, A8MTB9, A0A140LHF2, Q8BFR2, Q8N475, Q9PWR4, P35329, Q4VAH7, Q7TPB4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1094 predictions. Top by Δscore:

Variant	Effect	Δscore
19:41756598:A:AG	acceptor_gain	1.0000
19:41756599:G:GG	acceptor_gain	1.0000
19:41761247:AGC:A	acceptor_gain	1.0000
19:41761247:AGCG:A	acceptor_gain	1.0000
19:41761248:GC:G	acceptor_gain	1.0000
19:41761248:GCG:G	acceptor_gain	1.0000
19:41761248:GCGG:G	acceptor_gain	1.0000
19:41761248:GCGGA:G	acceptor_gain	1.0000
19:41761528:G:GG	donor_gain	1.0000
19:41769664:A:T	donor_gain	1.0000
19:41755687:G:GT	donor_gain	0.9900
19:41755699:ACAG:A	donor_loss	0.9900
19:41755703:GTG:G	donor_loss	0.9900
19:41756596:CTA:C	acceptor_loss	0.9900
19:41756597:TA:T	acceptor_loss	0.9900
19:41756598:AGCC:A	acceptor_loss	0.9900
19:41756599:G:GT	acceptor_loss	0.9900
19:41756599:GC:G	acceptor_gain	0.9900
19:41756599:GCC:G	acceptor_gain	0.9900
19:41756599:GCCT:G	acceptor_gain	0.9900
19:41756599:GCCTC:G	acceptor_gain	0.9900
19:41756958:CC:C	donor_gain	0.9900
19:41756960:G:GG	donor_gain	0.9900
19:41761244:CACA:C	acceptor_loss	0.9900
19:41761245:ACAGC:A	acceptor_gain	0.9900
19:41761246:C:G	acceptor_gain	0.9900
19:41761247:A:AC	acceptor_loss	0.9900
19:41761247:A:AG	acceptor_gain	0.9900
19:41761248:G:A	acceptor_loss	0.9900
19:41761248:G:GA	acceptor_gain	0.9900

AlphaMissense

2224 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41756734:T:A	W67R	0.956
19:41756734:T:C	W67R	0.956
19:41762160:T:A	C299S	0.942
19:41762161:G:C	C299S	0.942
19:41761467:T:A	C215S	0.941
19:41761468:G:C	C215S	0.941
19:41761500:A:C	S226R	0.941
19:41761502:T:A	S226R	0.941
19:41761502:T:G	S226R	0.941
19:41756855:T:C	L107P	0.939
19:41762076:T:A	W271R	0.939
19:41762076:T:C	W271R	0.939
19:41756736:G:C	W67C	0.937
19:41756736:G:T	W67C	0.937
19:41761358:G:C	W178C	0.935
19:41761358:G:T	W178C	0.935
19:41762078:G:C	W271C	0.928
19:41762078:G:T	W271C	0.928
19:41761356:T:A	W178R	0.927
19:41761356:T:C	W178R	0.927
19:41762040:T:C	C259R	0.913
19:41762160:T:C	C299R	0.912
19:41761467:T:C	C215R	0.911
19:41756893:T:G	Y120D	0.906
19:41762154:T:G	Y297D	0.898
19:41762040:T:A	C259S	0.897
19:41762041:G:C	C259S	0.897
19:41756900:T:C	L122P	0.895
19:41762174:C:A	N303K	0.895
19:41762174:C:G	N303K	0.895

dbSNP variants (sampled 300 via entrez): RS1000525945 (19:41762213 C>T), RS1000730833 (19:41757027 G>A,T), RS1001036404 (19:41756765 G>C), RS1001158937 (19:41765266 A>T), RS1001451553 (19:41768592 C>A), RS1001675785 (19:41759359 G>A), RS1002049838 (19:41769723 G>A), RS1002122407 (19:41771113 T>G), RS1002738943 (19:41766870 G>A,C), RS1003500039 (19:41767023 A>G), RS1003680958 (19:41754602 C>T), RS1003905590 (19:41754549 T>C), RS1004195276 (19:41766803 C>G), RS1004279104 (19:41754932 G>A), RS1004554134 (19:41764487 C>T)

Disease associations

OMIM: gene MIM:163980 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cystic fibrosis	Supportive	Autosomal recessive

Mondo (1): cystic fibrosis (MONDO:0009061)

Orphanet (0):

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Nephrolithiasis
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001508	Failure to thrive
HP:0001738	Exocrine pancreatic insufficiency
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002035	Rectal prolapse
HP:0002099	Asthma
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002570	Steatorrhea
HP:0002724	Recurrent Aspergillus infections
HP:0002726	Recurrent Staphylococcus aureus infections
HP:0002783	Recurrent lower respiratory tract infections
HP:0002842	Recurrent Burkholderia cepacia infections
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003251	Male infertility
HP:0004401	Meconium ileus
HP:0005376	Recurrent Haemophilus influenzae infections
HP:0006536	Airway obstruction
HP:0012236	Elevated sweat chloride

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009650_9	Serum carcinoembryonic antigen levels	5.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005760	serum carcinoembryonic antigen measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects cotreatment, affects expression, increases expression, increases methylation	3
Estradiol	increases expression, decreases expression, affects cotreatment	3
Calcitriol	increases expression	2
Lipopolysaccharides	decreases expression, affects expression, affects response to substance, affects cotreatment	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Tretinoin	increases expression	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
ascorbate-2-phosphate	affects cotreatment, increases expression, affects binding	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
beta-lapachone	increases expression	1
zinc chloride	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
tetrathiomolybdate	decreases expression	1
tanshinone	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
1-methylphenanthrene	affects cotreatment, affects expression	1
dibenzo(a,l)pyrene	affects expression, affects cotreatment	1
tamibarotene	increases expression, increases reaction, decreases expression, decreases reaction	1
indolo(3,2-b)carbazole	increases expression	1
CGP 52608	affects binding, increases reaction	1
azaspiracid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Chir 99021	affects binding, affects cotreatment, increases expression	1
clothianidin	increases expression	1
abrine	decreases expression	1
XAV939	increases expression, affects binding, affects cotreatment	1

Cellosaurus cell lines

3 cell lines: 2 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0EK	HEK293-CEACAM6-Fc	Transformed cell line	Female
CVCL_E6PX	Genomeditech CHO-K1 H_CEACAM6(CD66c)	Spontaneously immortalized cell line	Female
CVCL_E6TL	Genomeditech HEK-293 H_CEACAM6(CD66c)	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	PHASE4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	PHASE4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	PHASE4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	PHASE4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	PHASE4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	PHASE4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	PHASE4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	PHASE4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	PHASE4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	PHASE4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	PHASE4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	PHASE4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	PHASE4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	PHASE4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	PHASE4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	PHASE4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	PHASE4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	PHASE4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	PHASE4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	PHASE4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	PHASE4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	PHASE4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	PHASE4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	PHASE4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	PHASE4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	PHASE4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	PHASE4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	PHASE4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	PHASE4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	PHASE4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	PHASE4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	PHASE4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	PHASE4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis