CEACAM3

Summary

CEACAM3 (CEA cell adhesion molecule 3, HGNC:1815) is a protein-coding gene on chromosome 19q13.2, encoding Cell adhesion molecule CEACAM3 (P40198). Major granulocyte receptor mediating recognition and efficient opsonin-independent phagocytosis of CEACAM-binding microorganisms, including Neissiria, Moxarella and Haemophilus species, thus playing an important role in the clearance of pathogens by the innate immune system.

This gene encodes a member of the family of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), which are used by several bacterial pathogens to bind and invade host cells. The encoded transmembrane protein directs phagocytosis of several bacterial species that is dependent on the small GTPase Rac. It is thought to serve an important role in controlling human-specific pathogens by the innate immune system. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 1084 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cystic fibrosis (Supportive, GenCC)
• Clinical variants (ClinVar): 58 total
• GTEx eGene: eQTL in 6 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 35
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.36 (unconstrained)
• MANE Select transcript: NM_001815
• Notable: 58 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1815
Approved symbol	CEACAM3
Name	CEA cell adhesion molecule 3
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CD66d, CGM1a
Ensembl gene	ENSG00000170956
Ensembl biotype	protein_coding
OMIM	609142
Entrez	1084

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000357396

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 3: 1, TSL 4: 1, TSL 5: 3

ENST00000357396, ENST00000344550, ENST00000415495, ENST00000595255, ENST00000596544, ENST00000599305, ENST00000599662, ENST00000630848, ENST00000975347, ENST00000975348, ENST00001094475, ENST00001120357

RefSeq mRNA: 2 — MANE Select: NM_001815 NM_001277163, NM_001815

CCDS: CCDS12586, CCDS62685

Canonical transcript exons

ENST00000357396 — 7 exons

Exon	Start	End
ENSE00001847449	41796587	41796741
ENSE00003568592	41808813	41808930
ENSE00003604849	41797589	41797948
ENSE00003616653	41810323	41810354
ENSE00003623311	41809965	41810017
ENSE00003639986	41811172	41811554
ENSE00003676341	41810832	41810897

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 93.64.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.8476 / max 820.3614, expressed in 160 samples.

Highest expression (Bgee): blood, granulocyte, bone marrow, diaphragm, bone marrow cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CEACAM3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	sqtl	3.0e-23	+0.42	19:41817308:C:T
Esophagus Mucosa	eqtl	1.2e-22	-0.42	19:41802009:A:G
Colon Transverse	eqtl	2.2e-13	-0.35	19:41802009:A:G
Whole Blood	eqtl	1.1e-12	-0.17	19:41811775:T:C
Lung	eqtl	3.2e-11	-0.20	19:41802394:G:A
Lung	sqtl	1.5e-03	+0.36	19:41781584:A:G
Small Intestine Terminal Ileum	eqtl	6.2e-03	-0.38	19:41790017:G:A
Nerve Tibial	eqtl	3.2e-02	-0.53	19:41664001:T:G

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
176061	3.0381	147
208832	0.2904	17
176062	0.2667	40
176063	0.2351	16
208831	0.0173	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	93.64	gold quality
granulocyte	CL:0000094	89.35	gold quality
bone marrow	UBERON:0002371	87.60	gold quality
diaphragm	UBERON:0001103	87.43	gold quality
bone marrow cell	CL:0002092	86.74	gold quality
pancreatic ductal cell	CL:0002079	86.57	silver quality
periodontal ligament	UBERON:0008266	84.79	gold quality
leukocyte	CL:0000738	82.86	gold quality
type B pancreatic cell	CL:0000169	82.58	gold quality
monocyte	CL:0000576	82.34	gold quality
hair follicle	UBERON:0002073	82.26	gold quality
mononuclear cell	CL:0000842	82.24	gold quality
olfactory bulb	UBERON:0002264	81.87	gold quality
epithelial cell of pancreas	CL:0000083	81.71	gold quality
spleen	UBERON:0002106	81.02	gold quality
endometrium epithelium	UBERON:0004811	80.84	gold quality
vastus lateralis	UBERON:0001379	80.56	gold quality
quadriceps femoris	UBERON:0001377	80.25	gold quality
tibialis anterior	UBERON:0001385	79.16	silver quality
tongue squamous epithelium	UBERON:0006919	78.79	gold quality
triceps brachii	UBERON:0001509	77.30	gold quality
myocardium	UBERON:0002349	76.97	gold quality
vena cava	UBERON:0004087	76.77	gold quality
mucosa of transverse colon	UBERON:0004991	76.64	gold quality
gluteal muscle	UBERON:0002000	76.56	gold quality
trabecular bone tissue	UBERON:0002483	76.47	gold quality
deltoid	UBERON:0001476	76.13	gold quality
thymus	UBERON:0002370	75.89	gold quality
caecum	UBERON:0001153	75.79	gold quality
orbitofrontal cortex	UBERON:0004167	75.73	gold quality
vermiform appendix	UBERON:0001154	75.71	gold quality
nasal cavity epithelium	UBERON:0005384	75.14	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.93	gold quality
left ventricle myocardium	UBERON:0006566	74.88	gold quality
CA1 field of hippocampus	UBERON:0003881	74.66	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.46	gold quality
cardia of stomach	UBERON:0001162	73.39	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	73.33	gold quality
cervix squamous epithelium	UBERON:0006922	73.24	gold quality
pericardium	UBERON:0002407	72.86	gold quality
ileal mucosa	UBERON:0000331	72.77	silver quality
saphenous vein	UBERON:0007318	72.64	gold quality
pharyngeal mucosa	UBERON:0000355	72.59	gold quality
subthalamic nucleus	UBERON:0001906	72.50	gold quality
dorsal plus ventral thalamus	UBERON:0001897	72.30	gold quality
nipple	UBERON:0002030	72.16	gold quality
body of tongue	UBERON:0011876	72.15	gold quality
tongue	UBERON:0001723	72.11	gold quality
secondary oocyte	CL:0000655	71.90	silver quality
muscle tissue	UBERON:0002385	71.90	gold quality
lateral globus pallidus	UBERON:0002476	71.76	gold quality
biceps brachii	UBERON:0001507	71.72	gold quality
trachea	UBERON:0003126	71.59	gold quality
mammary duct	UBERON:0001765	71.51	gold quality
epithelium of esophagus	UBERON:0001976	71.45	gold quality
substantia nigra pars compacta	UBERON:0001965	71.36	gold quality
superior surface of tongue	UBERON:0007371	71.24	gold quality
substantia nigra pars reticulata	UBERON:0001966	71.13	gold quality
superficial temporal artery	UBERON:0001614	70.95	gold quality
rectum	UBERON:0001052	70.93	gold quality
cervix epithelium	UBERON:0004801	70.78	gold quality
heart right ventricle	UBERON:0002080	70.77	gold quality
synovial joint	UBERON:0002217	70.67	silver quality
pylorus	UBERON:0001166	70.63	gold quality
lateral nuclear group of thalamus	UBERON:0002736	70.60	gold quality
pons	UBERON:0000988	70.52	gold quality
squamous epithelium	UBERON:0006914	70.49	gold quality
right lung	UBERON:0002167	70.34	gold quality
epithelium of mammary gland	UBERON:0003244	70.31	gold quality
upper lobe of left lung	UBERON:0008952	70.20	gold quality
renal medulla	UBERON:0000362	70.06	gold quality
trigeminal ganglion	UBERON:0001675	70.05	gold quality
superior vestibular nucleus	UBERON:0007227	69.95	gold quality
parietal lobe	UBERON:0001872	69.88	gold quality
entorhinal cortex	UBERON:0002728	69.77	gold quality
Brodmann (1909) area 10	UBERON:0013541	69.74	gold quality
penis	UBERON:0000989	69.70	gold quality
mucosa of urinary bladder	UBERON:0001259	69.65	gold quality
postcentral gyrus	UBERON:0002581	69.52	gold quality
kidney epithelium	UBERON:0004819	69.48	gold quality
esophagus squamous epithelium	UBERON:0006920	69.33	gold quality
medulla oblongata	UBERON:0001896	69.32	gold quality
cerebellar vermis	UBERON:0004720	69.29	gold quality
Brodmann (1909) area 46	UBERON:0006483	69.14	gold quality
lower esophagus mucosa	UBERON:0035834	68.83	gold quality
upper lobe of lung	UBERON:0008948	68.37	gold quality
buccal mucosa cell	CL:0002336	68.33	gold quality
upper arm skin	UBERON:0004263	67.95	gold quality
epithelium of nasopharynx	UBERON:0001951	67.83	gold quality
nephron tubule	UBERON:0001231	67.58	gold quality
urethra	UBERON:0000057	67.53	gold quality
renal glomerulus	UBERON:0000074	67.26	gold quality
colonic mucosa	UBERON:0000317	67.23	gold quality
palpebral conjunctiva	UBERON:0001812	67.17	silver quality
metanephric glomerulus	UBERON:0004736	66.90	gold quality
jejunum	UBERON:0002115	66.65	gold quality
esophagus mucosa	UBERON:0002469	66.65	gold quality
gingival epithelium	UBERON:0001949	66.23	gold quality
gingiva	UBERON:0001828	65.97	gold quality
cartilage tissue	UBERON:0002418	65.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	133.54
E-MTAB-9801	yes	8.31
E-ANND-3	yes	5.55

HPA expression

RNA tissue specificity: Tissue enriched

34 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	41.8	medium
Appendix	tissue	4.8	high
Spleen	tissue	2.2	low
Cerebral cortex	tissue	1.9	not detected
Tongue	tissue	1.2
Urinary bladder	tissue	0.9	not detected
Adipose tissue	tissue	0.8	not detected
Pons	tissue	0.7
Choroid plexus	tissue	0.7
Liver	tissue	0.6	not detected
Thymus	tissue	0.6
Lung	tissue	0.4	low
Tonsil	tissue	0.4	medium
Heart muscle	tissue	0.3	not detected
Placenta	tissue	0.3	low
Gallbladder	tissue	0.3	not detected
Lymph node	tissue	0.2	medium
Vagina	tissue	0.2	not detected
Rectum	tissue	0.2	medium
Smooth muscle	tissue	0.2	not detected
Colon	tissue	0.2	medium
Pancreas	tissue	0.2	not detected
Endometrium 1	tissue	0.2	not detected
Cervix	tissue	0.1	not detected
Breast	tissue	0.1	not detected
Esophagus	tissue	0.1	not detected
Basal ganglia	tissue	0.1	not detected
Thalamus	tissue	0.1
Small intestine	tissue	0.1	not detected
Adrenal gland	tissue	0.1	not detected
Stomach 1	tissue	0.0	low
Salivary gland	tissue	0.0	low
Parathyroid gland	tissue	0.0	low
Thyroid gland	tissue	0.0	low

Brain sub-regions (HPA Brain Atlas): detected in 9; highest nTPM — Area parastriata, superior (1.9), Ventrolateral tegmental area, A5 NE cell group (0.7), Parietal operculum (0.2), Blood vessel (0.1), Dorsal tegmental nucleus (0.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

Targeting CEACAM3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

6 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-3664-3P	97.85	67.62	1452

Functional genomics

gnomAD constraint: pLI 3.76e-10, LOEUF 1.36, missense Z 0.66 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000357396 — one region, missense o/e 0.92.

Literature-anchored findings (GeneRIF, showing 34)

• CEACAM3 has a role in internalizing bacteria to epithelial cells (PMID:12571236)
• CEACAM3 controls human-specific pathogens by the innate immune system. (PMID:14707113)
• Molecular staging of SLN using real-time RT-PCR for early breast cancer could serve as a useful complement to standard clinicopathological risk factors. (PMID:17071045)
• Increased p53, CEA, and CA 19-9 serum levels are associated with colorectal cancer. (PMID:17211733)
• 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)
• These data reveal CEACAM3 as a specific innate immune receptor that mediates the opsonin-independent clearance of CEACAM-binding bacteria via Syk, a molecular trigger for functional immunoreceptor responses of both the adaptive and innate immune systems. (PMID:17506820)
• killing of bulk NK cultures was inhibited by CEA-expressing cells, suggesting that this putative receptor is an inhibitory receptor (PMID:17878338)
• 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)
• Increased CA 19-9 level is associated with pancreatic adenocarcinoma and cholangiocarcinoma. (PMID:19089662)
• CEACAM6 and a regulatory element near the 3’ end of CEACAM3 are associated with cystic fibrosis disease severity and intrapair discordance (PMID:20047061)
• CA-19.9 serum tumor marker levels retain independent prognostic value for poor survival in patients with advanced pancreatic cancer. (PMID:20071292)
• the prognostic value of preoperative serum carbohydrate antigen19-9, carcinoembryonic antigen, and carbohydrate antigen 125 for overall survival in patients with colorectal cancer was studied (PMID:20373053)
• the ability of CEACAM3 to coordinate signaling events that not only mediate bacterial uptake, but also trigger the killing of internalized pathogens. (PMID:21216968)
• 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)
• The higher expression of CD44v6, integrin-beta1, CA199, and CEA are closely related to the progression and metastasis of pancreatic cancer.[CA199, CD44v6] (PMID:22382453)
• CEACAM3 promotes opsonin-independent phagocytosis of CEACAM-binding bacteria. CEACAM3 is the main driver for this process on human granulocytes. (PMID:22469950)
• Grb14 is the first negative regulator of CEACAM3-initiated bacterial phagocytosis and might help to focus granulocyte responses to the subcellular sites of pathogen-host cell contact (PMID:22948154)
• A failure of CEACAM3-mediated innate immune detection might be linked to the ability of gonococci to cause disseminated infections. (PMID:23630956)
• COLIV is a promising tumour marker for CLM and can possibly be used to detect postoperative CLM recurrence. The combination of COLIV and CEA is superior to either marker alone in detecting CLM (PMID:26162539)
• Demonstrated the CEACAM3 specificity and a perioperative trend of circulating tumor cells which is coherent with the clinical/pathological considerations in colorectal cancer. (PMID:26556959)
• CEACAM3 signalling in neutrophils is able to specifically modulate airway inflammation caused by infection with M. catarrhalis. (PMID:27038042)
• Opacity protein OpaI of Neisseria gonorrhoeae in lipooligosaccharide mutants lost ability to interact with neutrophil-restricted CEACAM3. (PMID:27376801)
• We demonstrate that recombinant Neisseria Opa proteins reconstituted into liposomes retain the ability to recognize and interact with CEACAM1 and 3 in vitro but do not maintain receptor specificity compared to that of Opa proteins natively expressed by Neisseria gonorrhoeae. (PMID:27442026)
• p-CEA measurement in patients with pleural effusion of uncertain etiology is a safe and cost-effective procedure, everywhere easily available, which may help clinicians in selecting patients for further evaluations (PMID:27521620)
• Helicobacter pylori HopQ binds the amino-terminal IgV-like domain of human CEACAM1, CEACAM3, CEACAM5 or CEACAM6 proteins, thereby enabling translocation of the major pathogenicity factor CagA into host cells. (PMID:27748756)
• Here, the authors identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of Helicobacter pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. (PMID:27748768)
• the findings reveal an integration of the specific innate immune receptor CEACAM3 into the network of more conventional pattern recognition receptors, providing a mechanism by which the innate immune system can unleash its response to a relentless pathogen. (PMID:28886618)
• Amino acid alterations found in CEACAM3 translate into characteristic binding patterns for bacterial adhesins. One such amino acid residue is F62 in human and chimp CEACAM3, which is critical for binding the OMP P1 adhesin of Haemophilus aegyptius. Incorporation of the F62-containing motif into gorilla CEACAM3 results in a gain-of-function phenotype with regard to phagocytosis of H. aegyptius. (PMID:30744974)
• High serum CEA expression is associated with systemic recurrence in colorectal cancer. (PMID:30852955)
• CEACAM3 decreases asthma exacerbations and modulates respiratory syncytial virus latent infection in children. (PMID:32606071)
• Antibody ligation of CEACAM1, CEACAM3, and CEACAM6, differentially enhance the cytokine release of human neutrophils in responses to Candida albicans. (PMID:34847408)
• Phagocytosis mediated by the human granulocyte receptor CEACAM3 is limited by the receptor-type protein tyrosine phosphatase PTPRJ. (PMID:35850306)
• Diffusion-weighted magnetic resonance sequence and CA125/CEA ratio can be used as add-on tools to ultrasound for the differentiation of ovarian from non-ovarian pelvic masses. (PMID:36928256)
• Pretreatment controlling nutritional status (CONUT) score and carcinoembryonic antigen level provide tumor progression and prognostic information in gastric cancer: A retrospective study. (PMID:38065858)

Cross-species orthologs

36 orthologs

Organism	Symbol	Gene ID
mus_musculus	Psg18	ENSMUSG00000003505
mus_musculus	Psg17	ENSMUSG00000004540
mus_musculus	Psg19	ENSMUSG00000004542
mus_musculus	Ceacam5	ENSMUSG00000008789
mus_musculus	Psg29	ENSMUSG00000023159
mus_musculus	Ceacam14	ENSMUSG00000023185
mus_musculus	Ceacam12	ENSMUSG00000030366
mus_musculus	Ceacam11	ENSMUSG00000030368
mus_musculus	Psg28	ENSMUSG00000030373
mus_musculus	Psg22	ENSMUSG00000044903
mus_musculus	Ceacam3	ENSMUSG00000053228
mus_musculus	Ceacam10	ENSMUSG00000054169
mus_musculus	Ceacam2	ENSMUSG00000054385
mus_musculus	Ceacam13	ENSMUSG00000057195
mus_musculus	Psg20	ENSMUSG00000063305
mus_musculus	Psg16	ENSMUSG00000066760
mus_musculus	Psg21	ENSMUSG00000070796
mus_musculus	Psg27	ENSMUSG00000070797
mus_musculus	Psg25	ENSMUSG00000070798
mus_musculus	Psg26	ENSMUSG00000070799
mus_musculus	Ceacam1	ENSMUSG00000074272
mus_musculus	Psg23	ENSMUSG00000074359
mus_musculus	Ceacam23	ENSMUSG00000078793
rattus_norvegicus	LOC102557244	ENSRNOG00000017519
rattus_norvegicus	Ceacam11	ENSRNOG00000017620
rattus_norvegicus	Ceacam1	ENSRNOG00000020578
rattus_norvegicus	Psgb1	ENSRNOG00000027288
rattus_norvegicus	Ceacam3	ENSRNOG00000027607
rattus_norvegicus	Psg29	ENSRNOG00000029485
rattus_norvegicus	LOC120098290	ENSRNOG00000034000
rattus_norvegicus	Psg19	ENSRNOG00000038101
rattus_norvegicus	Ceacam12	ENSRNOG00000042158
rattus_norvegicus	Ceacam4	ENSRNOG00000046222
rattus_norvegicus	Psg16	ENSRNOG00000062379
rattus_norvegicus	Cgm4	ENSRNOG00000062787
rattus_norvegicus	LOC102557319	ENSRNOG00000071114

Paralogs (24): CEACAM21 (ENSG00000007129), CEACAM7 (ENSG00000007306), CEACAM1 (ENSG00000079385), CEACAM6 (ENSG00000086548), CEACAM4 (ENSG00000105352), CEACAM5 (ENSG00000105388), PSG8 (ENSG00000124467), CEACAM8 (ENSG00000124469), HEPACAM (ENSG00000165478), PSG6 (ENSG00000170848), 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1347251) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 51 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased circulating insulin level	2
decreased mean corpuscular hemoglobin concentration	2
decreased susceptibility to Coronaviridae infection	2
increased leukocyte cell number	1
abnormal colon morphology	1
obese	1
polyphagia	1
increased circulating HDL cholesterol level	1
decreased litter size	1
abnormal coat/hair pigmentation	1
abnormal glucose homeostasis	1
decreased susceptibility to viral infection	1
abnormal T cell physiology	1
increased mean platelet volume	1
decreased circulating triglyceride level	1
abnormal cytokine secretion	1
decreased circulating chloride level	1
increased insulin secretion	1
increased lean body mass	1
increased incidence of tumors by chemical induction	1
abnormal vascular wound healing	1
decreased energy expenditure	1
decreased T cell number	1
decreased T cell proliferation	1
decreased circulating cholesterol level	1

+26 more (showing top 25).

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CEACAM5	protein-coding	1048
LYPD4	protein-coding	147719
CEACAM6	protein-coding	4680
CEACAM7	protein-coding	1087
MIR6797	ncRNA	102465478
RPS19	protein-coding	6223
DMRTC2	protein-coding	63946

Protein

Protein identifiers

Cell adhesion molecule CEACAM3 — P40198 (reviewed: P40198)

Alternative names: Carcinoembryonic antigen CGM1, Carcinoembryonic antigen-related cell adhesion molecule 3

All UniProt accessions (3): P40198, B7Z5B4, M0QXR5

UniProt curated annotations — full annotation on UniProt →

Function. Major granulocyte receptor mediating recognition and efficient opsonin-independent phagocytosis of CEACAM-binding microorganisms, including Neissiria, Moxarella and Haemophilus species, thus playing an important role in the clearance of pathogens by the innate immune system. Responsible for RAC1 stimulation in the course of pathogen phagocytosis.

Subunit / interactions. Interacts with S100A9/calprotectin. This interaction is calcium-dependent, but independent of CEACAM3 phosphorylation.

Subcellular location. Membrane.

Tissue specificity. CGM1a, the predominant CGM1 transcript, is granulocyte-specific. Not detected out of the granulocytic lineage, such as monocytes, lymphocytes, spleen, testis, colon, brain, liver, pancreas, thymus, ovary, placenta, skeletal muscle, prostate, small intestine, heart, lung and kidney.

Post-translational modifications. Tyrosine-phosphorylated in response to microbial binding. Tyr-230 and Tyr-241 are both required for phosphorylation to be detected.

Domain organisation. The cytosolic domain is involved in S100A9 interaction.

Similarity. Belongs to the immunoglobulin superfamily. CEA family.

Isoforms (3)

UniProt ID	Names	Canonical?
P40198-1	1, CGM1A	yes
P40198-2	2, CGM1B
P40198-3	3, CGM1C

RefSeq proteins (2): NP_001264092, NP_001806* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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

UniProt features (32 total): strand 9, sequence conflict 5, splice variant 2, mutagenesis site 2, topological domain 2, helix 2, glycosylation site 2, signal peptide 1, chain 1, sequence variant 1, turn 1, transmembrane region 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
6AVZ	Crystal structure of the HopQ-CEACAM3 WT complex	X-RAY DIFFRACTION	2.05
6AW1	Crystal structure of CEACAM3	X-RAY DIFFRACTION	2.1
6AW0	Crystal structure of CEACAM3 L44Q	X-RAY DIFFRACTION	2.43
6AW3	Crystal structure of the HopQ-CEACAM3 L44Q complex	X-RAY DIFFRACTION	2.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40198-F1	78.52	0.53

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Functional residue map

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

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	104, 111

Mutagenesis-validated functional residues (2)

Position	Phenotype
230	loss of phosphorylation and 30% reduction in bacterial uptake. more than 60% reduction in bacterial uptake and loss of rac1 stimulation …
241	loss of phosphorylation and 30% reduction in bacterial uptake. more than 60% reduction in bacterial uptake and loss of rac1 stimulation …

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-202733	Cell surface interactions at the vascular wall	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—

MSigDB gene sets: 154 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, MODULE_45, GOCC_CELL_SURFACE, WEI_MYCN_TARGETS_WITH_E_BOX, MODULE_379, MODULE_88, MORF_PDPK1, MODULE_242, MODULE_11, MODULE_38, REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL, SHEN_SMARCA2_TARGETS_DN, GOCC_SECRETORY_VESICLE, MODULE_104

GO Biological Process (2): regulation of immune system process (GO:0002682), signal transduction (GO:0007165)

GO Molecular Function (2): protein tyrosine kinase binding (GO:1990782), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), cell surface (GO:0009986), specific granule membrane (GO:0035579), membrane (GO:0016020)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Hemostasis	1
Innate Immune System	1
Immune System	1

GO top-level categories

14 GO namespaces:

Category	Terms
cellular anatomical structure	2
immune system process	1
regulation of biological process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein kinase binding	1
binding	1
membrane	1
cell periphery	1
secretory granule membrane	1
specific granule	1

Protein interactions and networks

STRING

showing 15 of 558 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEACAM3	CYTH4	Q9UIA0	573
CEACAM3	A0A096LNM5	A0A096LNM5	520
CEACAM3	CEACAM20	Q6UY09	495
CEACAM3	ERV3-1	Q14264	463
CEACAM3	ERVFRD-1	P60508	460
CEACAM3	CYP2A7	P20853	447
CEACAM3	CYP2A13	Q16696	443
CEACAM3	CYP2A6	P00190	387
CEACAM3	SIGLEC5	O15389	371
CEACAM3	CD177	Q8N6Q3	368
CEACAM3	ALPK1	Q96QP1	360
CEACAM3	RAC2	P15153	359
CEACAM3	A1BG	P04217	344
CEACAM3	CEACAM19	Q7Z692	319
CEACAM3	SIGLEC14	Q08ET2	317

IntAct

Human interaction partners of CEACAM3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
CNIH3	physical association	0.560	3
NINJ1	physical association	0.560	3
NINJ2	physical association	0.560	3
PMP22	physical association	0.560	3

BioGRID (4 interactions; top human partners by supporting records): CNIH3 (Two-hybrid), NINJ1 (Two-hybrid), NINJ2 (Two-hybrid), PMP22 (Two-hybrid)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
PTPRJ	“down-regulates activity”	CEACAM3	dephosphorylation

Disease & clinical

Genetic variants

Variant evidence for CEACAM3: 58 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	8
Benign	8

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 644):

Position(s)	Effect	Δscore	Sites
19:41808928	donor_gain	1.0000
19:41797949–41797950	donor_loss	0.9900	5
19:41796742	donor_loss	0.9800	2
19:41797953	donor_loss	0.9800
19:41807308	donor_gain	0.9800
19:41808931–41808932	donor_loss	0.9800	6
19:41796742–41796743	donor_loss	0.9700	3
19:41809900	acceptor_gain	0.9700
19:41810018–41810019	donor_loss	0.9700	5
19:41807108	acceptor_gain	0.9600

AlphaMissense

165 missense substitutions predicted likely pathogenic (of 1,611 scored), across 67 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D116	8	0.830	0.907
W67	7	0.910	0.969
G70	6	0.744	0.847
E99	6	0.743	0.901
F138	5	0.889	0.917
Y120	5	0.816	0.930
G92	5	0.804	0.834
G48	5	0.685	0.797
N104	4	0.780	0.830
S106	4	0.779	0.938
Y65	4	0.760	0.900
G118	4	0.750	0.765
Y68	4	0.747	0.896
I79	4	0.744	0.869
S96	4	0.734	0.771
V51	4	0.719	0.770
G159	4	0.669	0.712
L107	3	0.895	0.958
I109	3	0.889	0.939
K69	3	0.850	0.900

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	0.000944

Disease associations

OMIM: gene MIM:609142 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
cystic fibrosis	Supportive	Autosomal recessive

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

HPO phenotypes

35 phenotypes (HPO-id order):

HPO	Term
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Kidney stone
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 infection
HP:0002726	Recurrent Staphylococcus aureus infection
HP:0002783	Recurrent lower respiratory tract infections
HP:0002842	Recurrent Burkholderia cepacia infection
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003251	Male infertility
HP:0004401	Meconium ileus
HP:0005376	Recurrent Haemophilus influenzae infection
HP:0006536	Airway obstruction
HP:0012236	Elevated sweat chloride
HP:0012873	Absent vas deferens
HP:0032261	Nontuberculous mycobacterial pulmonary infection
HP:0032342	Reduced forced expiratory volume in one second
HP:0045082	Decreased body mass index
HP:0100582	Nasal polyposis

MeSH disease descriptors

1 disease descriptors:

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 (CPIC guideline: no)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	3
bisphenol A	affects reaction, decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	increases expression	1
Aldehydes	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carmustine	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	affects reaction, decreases expression	1
Methotrexate	decreases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
1-Naphthylamine	affects response to substance	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0EI	HEK293-CEACAM3-Fc	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00157690	Phase 4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	Phase 4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	Phase 4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	Phase 4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	Phase 4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	Phase 4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	Phase 4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	Phase 4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	Phase 4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	Phase 4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	Phase 4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	Phase 4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	Phase 4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	Phase 4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	Phase 4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	Phase 4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	Phase 4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	Phase 4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	Phase 4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	Phase 4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	Phase 4	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	Phase 4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	Phase 4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	Phase 4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	Phase 4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	Phase 4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	Phase 4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	Phase 4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	Phase 4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	Phase 4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	Phase 4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	Phase 4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	Phase 4	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	Phase 4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	Phase 4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	Phase 4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	Phase 4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	Phase 4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	Phase 4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	Phase 4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis
NCT02178540	Phase 4	COMPLETED	Study to Validate the Instructions for Use of TOBI® Podhaler™ in Cystic Fibrosis Patients
NCT02277626	Phase 4	COMPLETED	Electro Flo 5000 and Vest Therapy
NCT02421120	Phase 4	COMPLETED	Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients
NCT02444234	Phase 4	COMPLETED	Pharmacokinetics of Tedizolid Phosphate in Cystic Fibrosis
NCT02504827	Phase 4	COMPLETED	Steady-state Pharmacokinetics of Ceftazidime/Avibactam in Cystic Fibrosis
NCT02547116	Phase 4	WITHDRAWN	Epidemiology and Treatment of Small-colony Variant Staphylococcus Aureus in Cystic Fibrosis
NCT02677701	Phase 4	COMPLETED	Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)
NCT02700282	Phase 4	COMPLETED	Backpack Carrying in Children With Cystic Fibrosis
NCT02823470	Phase 4	TERMINATED	A Pilot Study to Evaluate the Use of Smart Adherence Technology to Measure Lumacaftor/Ivacaftor Adherence in CF Subjects Homozygous for the F508del CFTR Mutation
NCT02823964	Phase 4	COMPLETED	EASY: Extended Access to Sollpura Over Years
NCT02875366	Phase 4	COMPLETED	A Study of the Effects of Lumacaftor/Ivacaftor (LUM/IVA) on Exercise Tolerance in Subjects With Cystic Fibrosis (CF), Homozygous for the F508del-CFTR Mutation
NCT02894684	Phase 4	COMPLETED	Aztreonam for Inhalation Solution (AZLI) for the Treatment of Exacerbations of Cystic Fibrosis
NCT02918409	Phase 4	COMPLETED	IV Colistin for Pulmonary Exacerbations: Improving Safety and Efficacy
NCT03045198	Phase 4	UNKNOWN	Effect of Azithromycin on Fatty Acids in CF
NCT03172793	Phase 4	COMPLETED	Telavancin Pharmacokinetics in Cystic Fibrosis Patients
NCT03256799	Phase 4	COMPLETED	Evaluation of Ivacaftor in Patients Using Ataluren for Nonsense Mutations
NCT03256968	Phase 4	COMPLETED	PTC Study to Evaluate Ataluren in Combination With Ivacaftor
NCT03502070	Phase 4	COMPLETED	Human Factors Study to Validate the User Interface of TOBI Podhaler Using Placebo Capsules
NCT03624101	Phase 4	TERMINATED	Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations
NCT03632525	Phase 4	COMPLETED	Intravenous Iron in Adults With Cystic Fibrosis