CEACAM8

Summary

CEACAM8 (CEA cell adhesion molecule 8, HGNC:1820) is a protein-coding gene on chromosome 19q13.2, encoding Cell adhesion molecule CEACAM8 (P31997). Cell surface glycoprotein that plays a role in cell adhesion in a calcium-independent manner.

Enables protein heterodimerization activity. Involved in heterophilic cell-cell adhesion. Located in cell surface and obsolete extracellular space. Biomarker of severe acute respiratory syndrome.

Source: NCBI Gene 1088 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 63 total
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.22 (unconstrained)
• MANE Select transcript: NM_001816
• Notable: 63 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1820
Approved symbol	CEACAM8
Name	CEA cell adhesion molecule 8
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CD66b
Ensembl gene	ENSG00000124469
Ensembl biotype	protein_coding
OMIM	615747
Entrez	1088

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000244336

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

ENST00000244336, ENST00000599005, ENST00000899996, ENST00000899997, ENST00001105429, ENST00001105430, ENST00001105431, ENST00001135242

RefSeq mRNA: 1 — MANE Select: NM_001816 NM_001816

CCDS: CCDS12610

Canonical transcript exons

ENST00000244336 — 6 exons

Exon	Start	End
ENSE00001415045	42583206	42583337
ENSE00001510272	42580243	42581353
ENSE00002430527	42588784	42589038
ENSE00002503260	42589457	42589735
ENSE00002516431	42594765	42594924
ENSE00002530103	42593541	42593900

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 99.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5140 / max 278.8940, expressed in 43 samples.

Highest expression (Bgee): trabecular bone tissue, bone marrow, bone marrow cell, male germ line stem cell (sensu Vertebrata) in testis, mononuclear cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CEACAM8 is not an eGene in any GTEx v10 tissue: no tissue shows a variant significantly associated with its expression or splicing (q < 0.05).

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
181202	0.2898	25
181203	0.2210	31
181204	0.0032	1

Top tissues by expression

showing 100 of 259 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.49	gold quality
bone marrow	UBERON:0002371	98.47	gold quality
bone marrow cell	CL:0002092	97.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.86	gold quality
mononuclear cell	CL:0000842	77.68	gold quality
monocyte	CL:0000576	77.51	gold quality
leukocyte	CL:0000738	76.84	gold quality
blood	UBERON:0000178	75.27	gold quality
granulocyte	CL:0000094	65.44	gold quality
spleen	UBERON:0002106	64.45	gold quality
mucosa of transverse colon	UBERON:0004991	61.18	gold quality
right lung	UBERON:0002167	61.03	gold quality
adrenal tissue	UBERON:0018303	55.06	gold quality
upper lobe of left lung	UBERON:0008952	50.95	gold quality
upper lobe of lung	UBERON:0008948	50.61	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
lung	UBERON:0002048	50.33	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
sural nerve	UBERON:0015488	50.24	silver quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
thymus	UBERON:0002370	49.99	silver quality
quadriceps femoris	UBERON:0001377	49.90	gold quality
vastus lateralis	UBERON:0001379	49.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
oviduct epithelium	UBERON:0004804	48.21	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
rectum	UBERON:0001052	47.96	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
epithelial cell of pancreas	CL:0000083	47.83	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
nasal cavity epithelium	UBERON:0005384	47.70	gold quality
amniotic fluid	UBERON:0000173	47.66	silver quality
renal glomerulus	UBERON:0000074	47.60	gold quality
layer of synovial tissue	UBERON:0007616	47.54	gold quality
kidney epithelium	UBERON:0004819	47.32	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
cortex of kidney	UBERON:0001225	46.87	silver quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
metanephros	UBERON:0000081	46.80	silver quality
colonic epithelium	UBERON:0000397	45.96	gold quality
deltoid	UBERON:0001476	45.91	gold quality
visceral pleura	UBERON:0002401	45.76	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
tibia	UBERON:0000979	45.31	silver quality
vermiform appendix	UBERON:0001154	45.14	silver quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	44.92	gold quality
lower lobe of lung	UBERON:0008949	44.89	silver quality
placenta	UBERON:0001987	44.78	gold quality
transverse colon	UBERON:0001157	44.63	gold quality
right lobe of liver	UBERON:0001114	44.51	gold quality
liver	UBERON:0002107	44.37	gold quality
connective tissue	UBERON:0002384	43.84	gold quality
trachea	UBERON:0003126	43.44	gold quality
squamous epithelium	UBERON:0006914	43.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
tibialis anterior	UBERON:0001385	43.34	silver quality
adipose tissue of abdominal region	UBERON:0007808	43.30	gold quality
adipose tissue	UBERON:0001013	43.07	gold quality
omental fat pad	UBERON:0010414	43.07	gold quality
peritoneum	UBERON:0002358	43.06	gold quality
epithelium of esophagus	UBERON:0001976	42.87	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
tonsil	UBERON:0002372	42.21	gold quality
cartilage tissue	UBERON:0002418	42.04	gold quality
medulla oblongata	UBERON:0001896	41.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	41.60	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
epithelium of mammary gland	UBERON:0003244	41.33	gold quality
ventricular zone	UBERON:0003053	41.22	gold quality
dorsal plus ventral thalamus	UBERON:0001897	41.20	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
embryo	UBERON:0000922	40.95	gold quality
superior frontal gyrus	UBERON:0002661	40.71	gold quality
colonic mucosa	UBERON:0000317	40.67	gold quality
mammary gland	UBERON:0001911	40.64	gold quality
thoracic mammary gland	UBERON:0005200	40.64	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
pancreatic ductal cell	CL:0002079	40.57	silver quality
biceps brachii	UBERON:0001507	40.57	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	3189.16
E-ANND-3	yes	12.17

HPA expression

RNA tissue specificity: Tissue enriched

41 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	204.8	medium
Cerebral cortex	tissue	5.2	not detected
Cerebellum	tissue	4.8	not detected
Amygdala	tissue	4.7
Occipital cortex	tissue	4.4
Hippocampal formation	tissue	4.1
Hypothalamus	tissue	4.0
Basal ganglia	tissue	3.9	not detected
Postcentral gyrus	tissue	3.9
Retrosplenial cortex	tissue	3.7
Hippocampus	tissue	3.6	not detected
Putamen	tissue	3.5
Pons	tissue	3.4
Thalamus	tissue	3.4
Nucleus accumbens	tissue	3.1
Midbrain	tissue	3.0
Medulla oblongata	tissue	3.0
Locus coeruleus	tissue	2.7
Substantia nigra	tissue	2.5
Spinal cord	tissue	2.4
Choroid plexus	tissue	1.6
Thymus	tissue	1.6
Lung	tissue	0.9	not detected
Spleen	tissue	0.9	high
Skin 1	tissue	0.4	not detected
Rectum	tissue	0.4	not detected
Colon	tissue	0.4	not detected
Placenta	tissue	0.4	not detected
Salivary gland	tissue	0.3	not detected
Pancreas	tissue	0.3	not detected
Lymph node	tissue	0.2	medium
Retina	tissue	0.2
Testis	tissue	0.1	not detected
Heart muscle	tissue	0.1	not detected
Adipose tissue	tissue	0.1	not detected
Skeletal muscle	tissue	0.1	not detected
Liver	tissue	0.1	not detected
Small intestine	tissue	0.1	not detected
Duodenum	tissue	0.1	not detected
Appendix	tissue	0.1	medium
Tonsil	tissue	0.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 184; highest nTPM — Posterior insular cortex (5.2), Vermis (4.8), Corticomedial amygdala (4.7), Inferior parietal lobule (4.6), Precentral gyrus (4.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CEACAM8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 71 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488

Functional genomics

gnomAD constraint: pLI 1.29e-09, LOEUF 1.22, missense Z 1.01 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000244336 — one region, missense o/e 0.89.

Literature-anchored findings (GeneRIF, showing 13)

• All the leukemic samples showed overexpression of CEACAM6 and 8 when compared with normal granulocytes. (PMID:17909799)
• CD66b molecules are involved in regulating adhesion and activation of eosinophils, possibly through their localization in lipid rafts and interaction with other cell surface molecules, such as CD11b. (PMID:18056392)
• 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)
• The highly elevated gene expression of CEACAM6 and CEACAM8 in primary myelofibrosis can serve as molecular markers of myelofibrotic transformation. (PMID:21470677)
• Granulocytes from type 2 diabetes patients display higher granulocyte cell surface expression of CD66b compared with values of healthy controls. (PMID:23686079)
• CEACAM8 interacts with CEACAM1 inhibiting TLR2-triggered immune responses (PMID:24743304)
• Inhibition of C5aR1 leads to a significant reduction of CD66b and CD11b expression indicating a lower neutrophil activation status and block of granule exocytosis. (PMID:26176669)
• Data suggest ways in which carcinoembryonic antigen-related cell adhesion molecules CEACAM6 and CEACAM8 regulate the biological functions of one another. (PMID:26483485)
• a 7-gene signature was identified which correctly predicted the primary prefibrotic myelofibrosis group with a sensitivity of 100% and a specificity of 89%. The 7 genes included MPO, CEACAM8, CRISP3, MS4A3, CEACAM6, HEMGN, and MMP8 (PMID:27579896)
• Increased CD66b positive tumor-infiltrating neutrophils (CD66b + TINs) was significantly associated with presence of metastasis, S stage, and nonseminomatous germ cell tumor diagnosis. (PMID:27863478)
• High CEACAM8 expression is associated with metastases in breast carcinoma. (PMID:31222613)
• CD66b(+) monocytes represent a proinflammatory myeloid subpopulation in cancer. (PMID:32632664)
• Clinical Significance of CD66b Expression in Non-Small Cell Lung Cancer. (PMID:37162631)

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), 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)

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).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gorilla gorilla gorilla	Q9N1E4	97.5%	Diamond
Pongo pygmaeus	Q9N1E3	92.5%	Diamond
Danio rerio	B0JYH6	60.9%	Diamond

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
MIR8077	ncRNA	102465875
MEGF8	protein-coding	1954
CXCL17	protein-coding	284340
LIPE	protein-coding	3991
CEACAM1	protein-coding	634
CNFN	protein-coding	84518
LIPE-AS1	ncRNA	100996307
PSG3	protein-coding	5671

Protein

Protein identifiers

Cell adhesion molecule CEACAM8 — P31997 (reviewed: P31997)

Alternative names: CD67 antigen, Carcinoembryonic antigen CGM6, Carcinoembryonic antigen-related cell adhesion molecule 8, Non-specific cross-reacting antigen NCA-95

All UniProt accessions (3): P31997, M0R1X3, Q0Z7S6

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface glycoprotein that plays a role in cell adhesion in a calcium-independent manner. Mediates heterophilic cell adhesion with other carcinoembryonic antigen-related cell adhesion molecules, such as CEACAM6. Heterophilic interaction with CEACAM8 occurs in activated neutrophils.

Subunit / interactions. Monomer. Heterodimer with CEACAM6; heterodimerizes via its Ig-like V-type domain.

Subcellular location. Cell membrane. Cell surface.

Tissue specificity. Expressed in leukocytes of chronic myeloid Leukemia patients and bone marrow.

Post-translational modifications. Glycosylated.

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

Similarity. Belongs to the immunoglobulin superfamily. CEA family.

RefSeq proteins (1): NP_001807* (*=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 (48 total): glycosylation site 11, mutagenesis site 10, strand 9, sequence variant 5, domain 3, disulfide bond 2, helix 2, turn 2, signal peptide 1, chain 1, propeptide 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
4Y88	Crystal structure of the N-terminal domain of CEACAM8	X-RAY DIFFRACTION	1.45
4YIQ	Structure of the CEACAM6-CEACAM8 heterodimer	X-RAY DIFFRACTION	1.85
4WTZ	Human CEACAM6-CEACAM8 N-domain heterodimer complex	X-RAY DIFFRACTION	2.52
2DKS	Solution structure of the first IG-like domain of human carcinoembryonic antigen related …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31997-F1	87.26	0.79

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Type	Positions
Gpi-anchor amidated aspartate	320

Disulfide bonds (2)

Type	Positions
Disulfide bond	167–215, 259–299

Glycosylation sites (11)

Type	Positions
N-linked (glcnac…) asparagine	152, 173, 197, 224, 256, 274, 288, 309, 104, 111, 115

Mutagenesis-validated functional residues (10)

Position	Phenotype
40–45	no effect on heterophilic cell adhesion.
61–63	no effect on heterophilic cell adhesion.
66	inhibits heterophilic cell adhesion.
72–75	no effect on heterophilic cell adhesion.
78	does not affect the monomeric structure. loss of heterodimerization with ceacam6.
78	inhibits heterophilic cell adhesion.
85–89	no effect on heterophilic cell adhesion.
97	no effect on heterophilic cell adhesion.
123	does not affect the monomeric structure. decreases heterodimerization with ceacam6.
129	does not affect the monomeric structure. loss of heterodimerization with ceacam6.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

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

MSigDB gene sets: 81 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOCC_CELL_SURFACE, GOBP_CELL_CELL_ADHESION, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, VALK_AML_CLUSTER_15, REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL, GOCC_SECRETORY_VESICLE, GOCC_SPECIFIC_GRANULE, GOCC_SECRETORY_GRANULE_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY

GO Biological Process (4): immune response (GO:0006955), homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), cell adhesion (GO:0007155)

GO Molecular Function (2): protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), cell surface (GO:0009986), azurophil granule membrane (GO:0035577), specific granule membrane (GO:0035579), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), side of membrane (GO:0098552)

Reactome top-level categories

4 top-level categories:

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

GO top-level categories

16 GO namespaces:

Category	Terms
secretory granule membrane	3
cell-cell adhesion	2
membrane	2
cellular anatomical structure	2
immune system process	1
response to stimulus	1
cellular process	1
protein dimerization activity	1
binding	1
cell periphery	1
lysosomal membrane	1
azurophil granule	1
specific granule	1
extracellular vesicle	1
tertiary granule	1
leaflet of membrane bilayer	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
heterophilic cell-cell adhesion	BP	mutant phenotype
cell surface	CC	direct assay
extracellular exosome	CC	high-throughput assay
protein heterodimerization activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,218 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEACAM8	FUT4	P22083	771
CEACAM8	FCGR3B	O75015	756
CEACAM8	ITGAM	P11215	755
CEACAM8	FCGR3A	P08637	751
CEACAM8	CD33	P20138	716
CEACAM8	CD19	P15391	702
CEACAM8	NCAM1	P13591	701
CEACAM8	PTPRC	P08575	678
CEACAM8	GYPA	P02724	654
CEACAM8	CD177	Q8N6Q3	637
CEACAM8	CD8A	P01732	622
CEACAM8	SELL	P14151	621
CEACAM8	MPO	P05164	607
CEACAM8	CD4	P01730	601
CEACAM8	ELANE	P08246	577

IntAct

Human interaction partners of CEACAM8 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
CEACAM6	direct interaction	0.820	8
CEACAM1	physical association	0.710	3
ZNF16	physical association	0.370	1
ZPLD1	association	0.350	2
HS3ST1	association	0.350	1
PRRT4	association	0.350	1
VGF	association	0.350	1

BioGRID (120 interactions; top human partners by supporting records): CEACAM1 (Reconstituted Complex; 2 records), ZPLD1 (Affinity Capture-MS; 2 records), ADAM9 (Affinity Capture-MS), APOE (Affinity Capture-MS), ARSK (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT3 (Affinity Capture-MS), BCKDHB (Affinity Capture-MS), BMP7 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D3 (Affinity Capture-MS), CEACAM6 (Reconstituted Complex), CELSR3 (Affinity Capture-MS), CERCAM (Affinity Capture-MS), CES3 (Affinity Capture-MS)

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CEACAM6	ligand	Adhesion by CEAM
CEACAM1	receptor	Adhesion by CEAM

Disease & clinical

Genetic variants

Variant evidence for CEACAM8: 63 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	5
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 557):

Position(s)	Effect	Δscore	Sites
19:42589738	acceptor_gain	0.9900
19:42589736–42589737	acceptor_loss	0.9800	6
19:42589742	acceptor_gain	0.9700
19:42594763–42594764	donor_loss	0.9700	5
19:42589452	donor_loss	0.9600	2
19:42589455–42589456	donor_loss	0.9600	5
19:42589452	donor_loss	0.9500
19:42589455	donor_loss	0.9500
19:42589451	donor_loss	0.9400
19:42589453	donor_loss	0.9300

AlphaMissense

264 missense substitutions predicted likely pathogenic (of 2,260 scored), across 92 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
W67	7	0.937	0.983
C167	7	0.900	0.942
C215	7	0.896	0.961
W178	7	0.873	0.962
W271	7	0.840	0.945
C259	7	0.812	0.886
C299	7	0.771	0.869
D116	7	0.764	0.824
G92	6	0.852	0.934
S226	6	0.837	0.928
Y120	5	0.878	0.959
F138	5	0.874	0.914
G236	5	0.793	0.879
Y213	5	0.756	0.901
N303	5	0.738	0.909
Y297	5	0.711	0.841
S263	4	0.789	0.854
Y68	4	0.772	0.867
E158	4	0.772	0.880
S106	4	0.765	0.955

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:615747 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
fluorene-9-bisphenol	decreases expression	1
titanium dioxide	increases expression	1
ceric oxide	increases expression	1
tamibarotene	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
reparixin	decreases reaction, increases expression	1
Allergens	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1
Vanadium	increases expression	1
Zinc Oxide	increases expression	1
Coal Ash	increases 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_C0EL	HEK293-CEACAM8-Fc	Transformed cell line	Female

Clinical trials (associated diseases)

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