CEACAM4

Summary

CEACAM4 (CEA cell adhesion molecule 4, HGNC:1816) is a protein-coding gene on chromosome 19q13.2, encoding Cell adhesion molecule CEACAM4 (O75871). Granulocyte orphan receptor that acts as an trigger efficient phagocytosis of attached particles.

Predicted to enable protein tyrosine kinase binding activity. Involved in phagocytosis. Predicted to be located in membrane. Predicted to be active in cell surface and plasma membrane.

Source: NCBI Gene 1089 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_001817

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1816
Approved symbol	CEACAM4
Name	CEA cell adhesion molecule 4
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000105352
Ensembl biotype	protein_coding
OMIM	619159
Entrez	1089

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000221954, ENST00000472081, ENST00000600925, ENST00000902906

RefSeq mRNA: 4 — MANE Select: NM_001817 NM_001362492, NM_001362493, NM_001362495, NM_001817

CCDS: CCDS33033

Canonical transcript exons

ENST00000221954 — 7 exons

Exon	Start	End
ENSE00000708545	41625601	41625960
ENSE00000842460	41619670	41619711
ENSE00000842461	41620211	41620242
ENSE00001322806	41619015	41619395
ENSE00002493926	41621651	41621768
ENSE00002514344	41620575	41620627
ENSE00003554911	41626900	41627074

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 95.65.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1596 / max 431.5855, expressed in 241 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181082	2.9506	226
181081	0.2090	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	95.65	gold quality
monocyte	CL:0000576	89.71	gold quality
spleen	UBERON:0002106	89.46	gold quality
leukocyte	CL:0000738	89.36	gold quality
granulocyte	CL:0000094	87.54	gold quality
bone marrow	UBERON:0002371	85.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.26	silver quality
bone marrow cell	CL:0002092	81.48	gold quality
vermiform appendix	UBERON:0001154	81.21	gold quality
right lung	UBERON:0002167	80.83	gold quality
upper lobe of left lung	UBERON:0008952	73.50	gold quality
lymph node	UBERON:0000029	67.02	gold quality
lung	UBERON:0002048	66.74	gold quality
smooth muscle tissue	UBERON:0001135	66.17	gold quality
gall bladder	UBERON:0002110	66.02	gold quality
right coronary artery	UBERON:0001625	65.92	gold quality
left uterine tube	UBERON:0001303	65.33	gold quality
descending thoracic aorta	UBERON:0002345	64.63	gold quality
placenta	UBERON:0001987	63.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	62.45	gold quality
mucosa of stomach	UBERON:0001199	62.24	gold quality
omental fat pad	UBERON:0010414	61.84	gold quality
small intestine	UBERON:0002108	61.46	gold quality
left coronary artery	UBERON:0001626	61.07	gold quality
duodenum	UBERON:0002114	60.83	gold quality
esophagus mucosa	UBERON:0002469	60.53	gold quality
adipose tissue	UBERON:0001013	60.39	gold quality
heart left ventricle	UBERON:0002084	60.35	gold quality
tibial nerve	UBERON:0001323	59.78	gold quality
body of pancreas	UBERON:0001150	59.30	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting CEACAM4, 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-488-5P	99.28	68.12	821
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-4468	98.01	66.85	1187

Literature-anchored findings (GeneRIF, showing 2)

• CEACAM4 is expressed in tumor-derived cell lines, and this expression is specific to an medullary thyroid carcinoma derived cell line. (PMID:25152032)
• CEACAM4 has phagocytic function. (PMID:25567962)

Cross-species orthologs

0 orthologs

Paralogs (24): CEACAM21 (ENSG00000007129), CEACAM7 (ENSG00000007306), CEACAM1 (ENSG00000079385), CEACAM6 (ENSG00000086548), 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 CEACAM4 — O75871 (reviewed: O75871)

Alternative names: Carcinoembryonic antigen CGM7, Carcinoembryonic antigen-related cell adhesion molecule 4, Non-specific cross-reacting antigen W236

All UniProt accessions (2): O75871, M0R363

UniProt curated annotations — full annotation on UniProt →

Function. Granulocyte orphan receptor that acts as an trigger efficient phagocytosis of attached particles.

Subunit / interactions. Interacts through its phosphorylated ITAM domain with the SH2 domain-containing cytoplasmic proteins involved in signaling processes during phagocytosis.

Subcellular location. Membrane.

Tissue specificity. Granulocytes.

Post-translational modifications. N-glycosylated. The cytoplasmic ITAM-like sequence becomes tyrosine phosphorylated by SRC family PTKs upon ligand-mediated receptor clustering and allows to initiate phagocytosis of bound ligand.

Miscellaneous. To study the function of the orphan receptor CEACAM4 chimeric proteins containing the extracellular bacteria-binding domain of CEACAM3 and the transmembrane and cytoplasmic part of CEACAM4 has been used.

Similarity. Belongs to the immunoglobulin superfamily. CEA family.

RefSeq proteins (4): NP_001349421, NP_001349422, NP_001349424, NP_001808* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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

UniProt features (18 total): glycosylation site 4, sequence variant 2, mutagenesis site 2, sequence conflict 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75871-F1	76.99	0.51

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 (4): 111, 126, 57, 104

Mutagenesis-validated functional residues (2):

Position	Phenotype
222	no internalization of bacteria; when associated with f-233.
233	no internalization of bacteria; when associated with f-222.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 63 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, TSENG_IRS1_TARGETS_UP, MODULE_45, MODULE_64, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, CAR_MYST2, MODULE_157, CAR_MLANA, SANSOM_APC_TARGETS_DN, AFFAR_YY1_TARGETS_DN, MODULE_242, GOBP_IMPORT_INTO_CELL, MODULE_20

GO Biological Process (3): regulation of immune system process (GO:0002682), phagocytosis (GO:0006909), signal transduction (GO:0007165)

GO Molecular Function (1): protein tyrosine kinase binding (GO:1990782)

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

1588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEACAM4	PLA2G7	Q13093	601
CEACAM4	CEACAM20	Q6UY09	600
CEACAM4	UNC79	Q9P2D8	575
CEACAM4	GK5	Q6ZS86	572
CEACAM4	NALCN	Q8IZF0	542
CEACAM4	UNC80	Q8N2C7	542
CEACAM4	CYP2A13	Q16696	521
CEACAM4	A0A096LNM5	A0A096LNM5	501
CEACAM4	CYP2A7	P20853	485
CEACAM4	FLT4	P35916	472
CEACAM4	CYP2A6	P00190	448
CEACAM4	CEACAM19	Q7Z692	434
CEACAM4	PDCD1LG2	Q9BQ51	420
CEACAM4	PTPRN2	Q92932	416
CEACAM4	IGDCC3	Q8IVU1	400

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PDCD1LG2	CEACAM4	psi-mi:“MI:0915”(physical association)	0.400
FLT4	CEACAM4	psi-mi:“MI:0915”(physical association)	0.400
CEACAM4	FLT4	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A0A0K2S4Q6, A2A7V7, A6NI73, A8K4G0, O43699, O75019, O75022, O75023, O75871, O76036, P0C191, P20138, P24071, P40198, P59901, P80943, Q08708, Q13410, Q28110, Q3U497, Q496F6, Q64JA4, Q6GTX8, Q6ISS4, Q6PI73, Q6UXZ3, Q7TSN2, Q863H2, Q8C567, Q8K249, Q8MJZ2, Q8MJZ7, Q8N149, Q8N423, Q8N6C8, Q8NHJ6, Q8NHL6, Q8VBT3, Q8VCH2, Q95JB9

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, A8MTB9, Q9D871, Q0E9H9, Q6UY09, A0A140LHF2, Q8BFR2, Q8N475, Q9PWR4, P35329, Q4VAH7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1063 predictions. Top by Δscore:

Variant	Effect	Δscore
19:41619946:A:AC	donor_gain	0.9900
19:41619947:C:CC	donor_gain	0.9900
19:41621653:T:A	donor_gain	0.9900
19:41625599:A:AC	donor_gain	0.9900
19:41625600:C:CC	donor_gain	0.9900
19:41626894:CCTCA:C	donor_loss	0.9900
19:41626895:CTCAC:C	donor_loss	0.9900
19:41626896:TCAC:T	donor_loss	0.9900
19:41626897:CAC:C	donor_loss	0.9900
19:41619712:C:CC	acceptor_gain	0.9800
19:41620567:ACACT:A	donor_loss	0.9800
19:41620568:CACT:C	donor_loss	0.9800
19:41620569:ACTC:A	donor_loss	0.9800
19:41620570:CT:C	donor_loss	0.9800
19:41620571:T:TG	donor_loss	0.9800
19:41620572:C:CC	donor_loss	0.9800
19:41620574:C:CG	donor_loss	0.9800
19:41620625:GCCC:G	acceptor_loss	0.9800
19:41620627:CCTAG:C	acceptor_loss	0.9800
19:41620628:C:CA	acceptor_loss	0.9800
19:41620629:T:C	acceptor_loss	0.9800
19:41620650:A:C	acceptor_gain	0.9800
19:41620709:C:CA	donor_gain	0.9800
19:41619707:GGGGC:G	acceptor_gain	0.9700
19:41619710:GCCT:G	acceptor_loss	0.9700
19:41619712:C:CA	acceptor_loss	0.9700
19:41619713:T:A	acceptor_loss	0.9700
19:41619923:AC:A	donor_gain	0.9700
19:41619924:CC:C	donor_gain	0.9700
19:41620573:A:AC	donor_gain	0.9700

AlphaMissense

1548 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41625824:C:A	W67C	0.984
19:41625824:C:G	W67C	0.984
19:41625709:A:G	S106P	0.975
19:41625826:A:G	W67R	0.972
19:41625826:A:T	W67R	0.972
19:41625711:C:T	G105E	0.965
19:41625667:A:C	Y120D	0.963
19:41625732:C:G	R98P	0.963
19:41625705:A:G	L107P	0.960
19:41625657:C:G	R123P	0.954
19:41625660:A:G	L122P	0.954
19:41625835:C:G	A64P	0.946
19:41625825:C:G	W67S	0.940
19:41625666:T:G	Y120S	0.936
19:41625711:C:A	G105V	0.932
19:41625667:A:T	Y120N	0.923
19:41625832:A:C	Y65D	0.922
19:41625867:A:G	L53P	0.918
19:41625699:A:G	F109S	0.914
19:41625728:C:A	E99D	0.912
19:41625728:C:G	E99D	0.912
19:41625625:C:G	A134P	0.900
19:41625667:A:G	Y120H	0.900
19:41625678:T:A	D116V	0.896
19:41625787:C:G	A80P	0.894
19:41625789:A:T	I79N	0.894
19:41625817:C:A	G70W	0.893
19:41625702:A:G	L108P	0.892
19:41625678:T:G	D116A	0.889
19:41625712:C:G	G105R	0.885

dbSNP variants (sampled 300 via entrez): RS1000199324 (19:41626321 C>T), RS1000331336 (19:41629036 G>T), RS1000354985 (19:41623424 T>G), RS1000686363 (19:41622399 C>T), RS1000870495 (19:41628868 T>A), RS1001070201 (19:41627727 C>T), RS1002392614 (19:41614999 G>C), RS1002971016 (19:41627191 C>A), RS1003048800 (19:41617295 G>A), RS1003109592 (19:41622324 C>T), RS1003236477 (19:41626094 G>A,T), RS1003392869 (19:41616093 G>A), RS1003977632 (19:41625654 G>A), RS1004018089 (19:41620851 G>A), RS1004992228 (19:41616087 T>A,C)

Disease associations

OMIM: gene MIM:619159 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004744_58	Lung adenocarcinoma	3.000000e-07
GCST007160_30	Refractive astigmatism	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	decreases expression	1
Aldehydes	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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