ESAM

Summary

ESAM (endothelial cell adhesion molecule, HGNC:17474) is a protein-coding gene on chromosome 11q24.2, encoding Endothelial cell-selective adhesion molecule (Q96AP7). Can mediate aggregation most likely through a homophilic molecular interaction.

Enables cell-cell adhesion mediator activity and identical protein binding activity. Involved in several processes, including bicellular tight junction assembly; cell-cell adhesion; and regulation of actin filament polymerization. Located in cell-cell junction and plasma membrane. Part of protein-containing complex.

Source: NCBI Gene 90952 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity (Definitive, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 92 total — 1 pathogenic, 7 likely-pathogenic
• GTEx eGene: eQTL in 8 tissues, sQTL in 9 (q < 0.05)
• Phenotypes (HPO): 93
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.01 (unconstrained)
• MANE Select transcript: NM_138961

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17474
Approved symbol	ESAM
Name	endothelial cell adhesion molecule
Location	11q24.2
Locus type	gene with protein product
Status	Approved
Aliases	W117m
Ensembl gene	ENSG00000149564
Ensembl biotype	protein_coding
OMIM	614281
Entrez	90952

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 18 nonsense_mediated_decay, 14 protein_coding, 2 retained_intron

MANE Select: ENST00000278927

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 1

ENST00000278927, ENST00000417453, ENST00000435477, ENST00000444566, ENST00000464067, ENST00000485116, ENST00000906450, ENST00000906451, ENST00000906452, ENST00000906453, ENST00000942605, ENST00000942606, ENST00000983026, ENST00000983027, ENST00000983028, ENST00000983029, ENST00000983030, ENST00000983031, ENST00000983032, ENST00000983033, ENST00001040710, ENST00001040711, ENST00001116004, ENST00001119392, ENST00001119393, ENST00001119394, ENST00001119395, ENST00001122791, ENST00001122792, ENST00001122793, ENST00001122794, ENST00001122795, ENST00001122796, ENST00001143214

RefSeq mRNA: 1 — MANE Select: NM_138961 NM_138961

CCDS: CCDS8453

Canonical transcript exons

ENST00000278927 — 7 exons

Exon	Start	End
ENSE00000991328	124756541	124756742
ENSE00001014314	124758349	124758527
ENSE00001695509	124762085	124762290
ENSE00003494011	124756207	124756362
ENSE00003561465	124753126	124753961
ENSE00003568182	124754641	124754763
ENSE00003665246	124754214	124754340

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 98.57.

FANTOM5 (CAGE): breadth broad, TPM avg 10.7628 / max 505.7369, expressed in 787 samples.

Highest expression (Bgee): lung, lobe of thyroid gland, upper lobe of left lung, coronary artery, popliteal artery.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ESAM is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 9 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	sqtl	2.6e-15	-0.29	11:124755762:C:T
Thyroid	sqtl	9.5e-08	-0.27	11:124755762:C:T
Cells EBV-transformed lymphocytes	eqtl	3.1e-06	-1.66	11:125522494:ATT:A
Adipose Subcutaneous	sqtl	3.3e-05	-0.24	11:124755762:C:T
Artery Aorta	eqtl	4.5e-05	-0.18	11:124146384:C:T
Nerve Tibial	sqtl	2.9e-04	-0.27	11:124755762:C:T
Adipose Visceral Omentum	sqtl	1.1e-03	-0.21	11:124755762:C:T
Lung	sqtl	1.3e-03	-0.22	11:124755762:C:T
Liver	sqtl	2.2e-03	-2.56	11:125366523:C:T
Breast Mammary Tissue	sqtl	4.2e-03	-0.27	11:124755762:C:T
Breast Mammary Tissue	eqtl	7.4e-03	+0.10	11:125542702:G:A
Artery Tibial	eqtl	1.5e-02	+0.33	11:125317541:A:G
Liver	eqtl	2.1e-02	-0.16	11:124935723:T:C
Heart Atrial Appendage	sqtl	2.2e-02	+1.28	11:124104743:T:A
Whole Blood	eqtl	3.6e-02	+0.26	11:124048247:A:G
Brain Nucleus accumbens basal ganglia	eqtl	3.8e-02	-0.26	11:125020693:T:C
Brain Frontal Cortex BA9	eqtl	4.2e-02	-0.54	11:123869997:G:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
122959	10.4986	732
122960	0.2641	63

Top tissues by expression

showing 100 of 251 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	98.57	gold quality
right lobe of thyroid gland	UBERON:0001119	98.47	gold quality
left lobe of thyroid gland	UBERON:0001120	98.40	gold quality
upper lobe of left lung	UBERON:0008952	98.35	gold quality
right coronary artery	UBERON:0001625	98.31	gold quality
popliteal artery	UBERON:0002250	98.12	gold quality
tibial artery	UBERON:0007610	98.12	gold quality
upper lobe of lung	UBERON:0008948	98.05	gold quality
thyroid gland	UBERON:0002046	97.88	gold quality
apex of heart	UBERON:0002098	97.69	gold quality
left coronary artery	UBERON:0001626	97.59	gold quality
omental fat pad	UBERON:0010414	97.34	gold quality
coronary artery	UBERON:0001621	97.27	gold quality
peritoneum	UBERON:0002358	97.27	gold quality
aorta	UBERON:0000947	96.74	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.72	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.06	gold quality
metanephros cortex	UBERON:0010533	95.99	gold quality
heart left ventricle	UBERON:0002084	95.40	gold quality
cardiac ventricle	UBERON:0002082	95.11	gold quality
ascending aorta	UBERON:0001496	95.10	gold quality
thoracic aorta	UBERON:0001515	95.09	gold quality
lung	UBERON:0002048	94.82	gold quality
tendon of biceps brachii	UBERON:0008188	94.69	gold quality
left uterine tube	UBERON:0001303	94.56	gold quality
heart	UBERON:0000948	94.39	gold quality
body of uterus	UBERON:0009853	94.24	gold quality
right atrium auricular region	UBERON:0006631	94.22	gold quality
placenta	UBERON:0001987	93.90	gold quality
cardiac atrium	UBERON:0002081	93.89	gold quality
kidney epithelium	UBERON:0004819	93.61	silver quality
descending thoracic aorta	UBERON:0002345	93.59	gold quality
endocervix	UBERON:0000458	93.40	gold quality
vena cava	UBERON:0004087	93.34	gold quality
adipose tissue	UBERON:0001013	93.22	gold quality
smooth muscle tissue	UBERON:0001135	93.18	gold quality
ectocervix	UBERON:0012249	93.14	gold quality
left ventricle myocardium	UBERON:0006566	92.35	silver quality
tibial nerve	UBERON:0001323	92.32	gold quality
lower esophagus	UBERON:0013473	92.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.16	gold quality
lower lobe of lung	UBERON:0008949	91.98	gold quality
saphenous vein	UBERON:0007318	91.79	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.71	gold quality
lower esophagus mucosa	UBERON:0035834	91.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.35	gold quality
gall bladder	UBERON:0002110	91.26	gold quality
adult mammalian kidney	UBERON:0000082	91.14	gold quality
monocyte	CL:0000576	91.12	gold quality
mucosa of stomach	UBERON:0001199	91.08	gold quality
metanephros	UBERON:0000081	90.96	gold quality
leukocyte	CL:0000738	90.25	gold quality
body of stomach	UBERON:0001161	90.25	gold quality
gastrocnemius	UBERON:0001388	90.22	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.04	silver quality
fundus of stomach	UBERON:0001160	90.01	gold quality
uterine cervix	UBERON:0000002	89.94	gold quality
esophagus	UBERON:0001043	89.89	gold quality
cortex of kidney	UBERON:0001225	89.86	gold quality
muscle of leg	UBERON:0001383	89.83	gold quality
pericardium	UBERON:0002407	89.69	gold quality
decidua	UBERON:0002450	89.67	gold quality
putamen	UBERON:0001874	89.34	gold quality
myocardium	UBERON:0002349	89.18	silver quality
myometrium	UBERON:0001296	89.16	gold quality
vagina	UBERON:0000996	89.11	gold quality
renal medulla	UBERON:0000362	88.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.46	gold quality
stomach	UBERON:0000945	88.45	gold quality
skeletal muscle organ	UBERON:0014892	88.29	gold quality
esophagus mucosa	UBERON:0002469	88.12	gold quality
skin of leg	UBERON:0001511	87.94	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.92	gold quality
right frontal lobe	UBERON:0002810	87.84	gold quality
kidney	UBERON:0002113	87.65	gold quality
anterior cingulate cortex	UBERON:0009835	87.49	gold quality
substantia nigra	UBERON:0002038	87.36	gold quality
amygdala	UBERON:0001876	87.34	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.29	gold quality
caudate nucleus	UBERON:0001873	87.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.14	gold quality
spinal cord	UBERON:0002240	87.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.06	gold quality
spleen	UBERON:0002106	86.82	gold quality
hypothalamus	UBERON:0001898	86.69	gold quality
left adrenal gland cortex	UBERON:0035825	86.58	gold quality
right ovary	UBERON:0002118	86.54	gold quality
minor salivary gland	UBERON:0001830	86.53	gold quality
adenohypophysis	UBERON:0002196	86.51	gold quality
right adrenal gland	UBERON:0001233	86.42	gold quality
prefrontal cortex	UBERON:0000451	86.34	gold quality
colonic epithelium	UBERON:0000397	86.30	gold quality
skin of abdomen	UBERON:0001416	86.30	gold quality
left adrenal gland	UBERON:0001234	86.28	gold quality
right uterine tube	UBERON:0001302	86.04	gold quality
midbrain	UBERON:0001891	85.99	gold quality
transverse colon	UBERON:0001157	85.98	gold quality
adrenal cortex	UBERON:0001235	85.83	gold quality
anatomical system	UBERON:0000467	85.65	gold quality
multicellular organism	UBERON:0000468	85.57	gold quality

Single-cell (SCXA)

Detected in 29 experiment(s), a significant marker in 29.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	1501.59
E-MTAB-10137	yes	1127.78
E-MTAB-8142	yes	1005.99
E-MTAB-9906	yes	860.16
E-MTAB-8221	yes	822.81
E-MTAB-8271	yes	775.50
E-ANND-5	yes	524.26
E-CURD-7	yes	432.71
E-ENAD-21	yes	412.20
E-GEOD-83139	yes	309.56
E-MTAB-10287	yes	79.91
E-GEOD-134144	yes	53.45
E-HCAD-1	yes	48.23
E-HCAD-11	yes	48.18
E-HCAD-10	yes	46.36

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Placenta	tissue	100.5	medium
Thyroid gland	tissue	73.6	medium
Lung	tissue	64.7	medium
Adipose tissue	tissue	51.3	not detected
Tongue	tissue	46.4
Heart muscle	tissue	34.5	medium
Vagina	tissue	28.1	low
Smooth muscle	tissue	27.5	medium
Frontal cortex	tissue	23.9
Caudate putamen	tissue	23.6
Skeletal muscle	tissue	21.8	not detected
Kidney	tissue	20.8	medium
Substantia nigra	tissue	19.3
Gallbladder	tissue	18.7	medium
Superior colliculi	tissue	18.3
Ovary	tissue	17.6	medium
Thalamus	tissue	17.3
Cervix	tissue	17.2	medium
Pons	tissue	17.1
Endometrium 1	tissue	16.9	medium
Esophagus	tissue	16.3	medium
Hippocampus	tissue	16.2	not detected
Cerebral cortex	tissue	16.1	medium
Insular cortex	tissue	16.1
Medulla oblongata	tissue	16.0
Locus coeruleus	tissue	15.8
Urinary bladder	tissue	15.7	medium
Spinal cord	tissue	15.7
Putamen	tissue	15.6
Midbrain	tissue	15.6
Motor cortex	tissue	15.3
Somatosensory cortex	tissue	14.9
Seminal vesicle	tissue	14.6	medium
Occipital cortex	tissue	14.6
Pituitary gland	tissue	14.4
Prefrontal cortex	tissue	14.3
Retrosplenial and cingulate cortex	tissue	14.2
Spleen	tissue	14.0	medium
Hippocampal formation	tissue	13.9
Postcentral gyrus	tissue	13.9
Entorhinal cortex	tissue	13.9
Temporal cortex	tissue	13.7
Retrosplenial cortex	tissue	12.9
Fallopian tube	tissue	12.7	medium
Nucleus accumbens	tissue	12.6
Parathyroid gland	tissue	12.4	medium
Basal ganglia	tissue	11.4	low
Stomach 1	tissue	11.1	medium
Hypothalamus	tissue	11.0
Septum	tissue	10.9
Ventral forebrain	tissue	10.8
Liver	tissue	10.7	medium
Corpus callosum	tissue	10.7
Amygdala	tissue	10.5
Pancreas	tissue	10.2	medium
Periaqueductal gray	tissue	9.5
Adrenal gland	tissue	8.8	medium
Olfactory bulb	tissue	8.8
Appendix	tissue	8.5	medium
Colon	tissue	8.3

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (99.9), Posterior thalamic nucleus (38.7), Dorsal cochlear nucleus (35.4), Reticulotegmental nucleus (29.4), Nucleus cuneatus (28.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

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

showing 30 of 41 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-4662A-5P	98.48	67.18	1007
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4483	98.09	64.12	1642

Functional genomics

gnomAD constraint: pLI 3.7e-07, LOEUF 1.01, missense Z 0.555 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000278927 — one region, missense o/e 0.98.

Literature-anchored findings (GeneRIF, showing 7)

• sESAM is a predictive biomarker and potential mediator of atherosclerosis. (PMID:19759376)
• ESAM regulates tumor metastasis through endothelial cell migration and tube formation in metastatic nodules. (PMID:20153339)
• sESAM is associated with albuminuria and reduced kidney function in patients with coronary artery disease in both cross-sectional and longitudinal analyses. (PMID:24177327)
• Serum ESAM is higher in type 2 diabetes mellitus than in controls and parallels oxidative stress. (PMID:24456423)
• sESAM levels associate with myocardial infarction, heart failure, and death after adjustment for demographic and clinical risk factors, but not after adjustment for kidney function. (PMID:26523992)
• ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias (PMID:26774386)
• Bi-allelic variants in the ESAM tight-junction gene cause a neurodevelopmental disorder associated with fetal intracranial hemorrhage. (PMID:36996813)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	esamb	ENSDARG00000076639
danio_rerio	esama	ENSDARG00000077039
danio_rerio	gpa33a	ENSDARG00000100223
mus_musculus	Esam	ENSMUSG00000001946
rattus_norvegicus	Esam	ENSRNOG00000033217

Paralogs (14): VSIG2 (ENSG00000019102), VSIG1 (ENSG00000101842), VSIR (ENSG00000107738), GPA33 (ENSG00000143167), IGSF11 (ENSG00000144847), CXADR (ENSG00000154639), JAM2 (ENSG00000154721), F11R (ENSG00000158769), MXRA8 (ENSG00000162576), JAM3 (ENSG00000166086), CLMP (ENSG00000166250), MUC15 (ENSG00000169550), VSTM2B (ENSG00000187135), VSIG8 (ENSG00000243284)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1916774) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	2
decreased tumor incidence	1
decreased vascular permeability	1
abnormal leukocyte migration	1
decreased angiogenesis	1
abnormal cellular extravasation	1

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
Macaca fascicularis	Q95KI3	96.4%	Diamond
Xenopus tropicalis	Q640U3	45.8%	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
ESAM-AS1	ncRNA	101929340
ROBO4	protein-coding	54538
ROBO3	protein-coding	64221
MSANTD2	protein-coding	79684
MSANTD2-AS1	ncRNA	100507283
NRGN-AS1	ncRNA	137233470
VSIG2	protein-coding	23584
NRGN	protein-coding	4900
SPA17	protein-coding	53340
SIAE	protein-coding	54414

Protein

Protein identifiers

Endothelial cell-selective adhesion molecule — Q96AP7 (reviewed: Q96AP7)

All UniProt accessions (3): Q96AP7, C9JIE7, F8WDW9

UniProt curated annotations — full annotation on UniProt →

Function. Can mediate aggregation most likely through a homophilic molecular interaction.

Subunit / interactions. Interacts with MAGI1.

Subcellular location. Cell junction. Adherens junction. Tight junction. Cell membrane.

Tissue specificity. Highly expressed in endothelial cells.

Disease relevance. Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity (NEDIHSS) [MIM:620371] An autosomal recessive disease characterized by prenatal or neonatal onset of intracranial hemorrhage, ventriculomegaly and cerebral calcifications. Affected individuals have profound global developmental delay, intellectual disability, epilepsy, absent or severely delayed speech, and varying degrees of spasticity. Death in utero or in early childhood may occur. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96AP7-1	1	yes
Q96AP7-2	2

RefSeq proteins (1): NP_620411* (*=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
IPR042757	ESAM	Family

Pfam: PF07686, PF13927

UniProt features (27 total): modified residue 7, glycosylation site 4, splice variant 3, topological domain 2, sequence variant 2, domain 2, signal peptide 1, chain 1, disulfide bond 1, sequence conflict 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AP7-F1	78.13	0.53

Human Protein Atlas

Protein class: Predicted membrane proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cell junctions; cytosol

Antibody reliability (HPA): IH uncertain · IF approved

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 (7)

Type	Positions
Phosphothreonine	332, 334
Phosphoserine	336, 339, 344, 371, 301

Disulfide bonds (1)

Type	Positions
Disulfide bond	174–224

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	108, 169, 213, 236

Function

Pathways and Gene Ontology

Reactome pathways

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

2 pathways:

ID	Pathway	Evidence
R-HSA-202733	Cell surface interactions at the vascular wall	curated
R-HSA-109582	Hemostasis	—

MSigDB gene sets: 421 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_APICAL_JUNCTION_ASSEMBLY, TGACCTY_ERR1_Q2, MEF2_02, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_UP, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, PU1_Q6

GO Biological Process (8): homophilic cell-cell adhesion (GO:0007156), intracellular protein localization (GO:0008104), regulation of actin filament polymerization (GO:0030833), regulation of actin cytoskeleton organization (GO:0032956), maintenance of blood-brain barrier (GO:0035633), bicellular tight junction assembly (GO:0070830), cell-cell adhesion (GO:0098609), cell adhesion (GO:0007155)

GO Molecular Function (3): identical protein binding (GO:0042802), cell-cell adhesion mediator activity (GO:0098632), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), bicellular tight junction (GO:0005923), protein-containing complex (GO:0032991), membrane (GO:0016020)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Hemostasis	1

GO top-level categories

24 GO namespaces:

Category	Terms
cell-cell adhesion	2
macromolecule localization	1
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
tissue homeostasis	1
apical junction assembly	1
tight junction assembly	1
cell adhesion	1
cellular process	1
protein binding	1
cell adhesion mediator activity	1
binding	1
membrane	1
cell periphery	1
anchoring junction	1
cell-cell junction	1
apical junction complex	1
tight junction	1
cellular_component	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
bicellular tight junction assembly	BP	mutant phenotype
cell-cell adhesion	BP	direct assay
intracellular protein localization	BP	direct assay
regulation of actin cytoskeleton organization	BP	direct assay
regulation of actin filament polymerization	BP	direct assay
cell-cell junction	CC	direct assay
plasma membrane	CC	direct assay
protein-containing complex	CC	direct assay
cell-cell adhesion mediator activity	MF	direct assay
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,098 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ESAM	VCAM1	P19320	724
ESAM	SELP	P16109	714
ESAM	SELE	P16111	713
ESAM	ICAM1	P05362	639
ESAM	PECAM1	P16284	639
ESAM	CLDN5	O00501	625
ESAM	CDH5	P33151	598
ESAM	TNF	P01375	580
ESAM	ATP1B1	P05026	580
ESAM	IGSF5	Q9NSI5	570
ESAM	JAML	Q86YT9	568
ESAM	EGFL7	Q9UHF1	568
ESAM	SELL	P14151	566
ESAM	ITGB2	P05107	563
ESAM	VWF	P04275	485

IntAct

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

3 partners by confidence:

Partner	Interaction type	MIscore	Records
TMBIM6	physical association	0.560	3
TTMP	physical association	0.560	3
TOP1	association	0.350	1

BioGRID (11 interactions; top human partners by supporting records): C3orf52 (Two-hybrid), CENPF (Affinity Capture-MS), ENG (Affinity Capture-MS), KIF14 (Affinity Capture-MS), MDC1 (Affinity Capture-MS), MPHOSPH8 (Affinity Capture-MS), MTDH (Protein-RNA), TMBIM6 (Two-hybrid), TOP1 (Affinity Capture-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
CLDN1-ESAM-OCLN-PECAM1 complex	4	PECAM1, CLDN1, ESAM, OCLN

Ligand–receptor pairs (CellPhoneDB) (1)

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

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ESAM	ligand

Disease & clinical

Genetic variants

Variant evidence for ESAM: 92 ClinVar records (8 pathogenic / likely pathogenic); 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	7
Uncertain significance	62
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (8)

Showing all 8 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4086789	NM_138961.3(ESAM):c.70+1G>T	Pathogenic	criteria provided, single submitter	1
1810270	NM_138961.3(ESAM):c.115del (p.Arg39fs)	Likely pathogenic	criteria provided, single submitter	2
1810271	NM_138961.3(ESAM):c.287del (p.Pro96fs)	Likely pathogenic	criteria provided, single submitter	2
1810272	NM_138961.3(ESAM):c.35T>A (p.Leu12Ter)	Likely pathogenic	criteria provided, single submitter	2
1810273	NM_138961.3(ESAM):c.451+1G>A	Likely pathogenic	criteria provided, single submitter	2
3065558	NM_138961.3(ESAM):c.949C>T (p.Arg317Ter)	Likely pathogenic	criteria provided, single submitter	1
4086169	NM_138961.3(ESAM):c.608-1G>A	Likely pathogenic	criteria provided, single submitter	1
4854072	NM_138961.3(ESAM):c.474C>A (p.Cys158Ter)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ESAM’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 684):

Position(s)	Effect	Δscore	Sites
11:124754212	donor_loss	1.0000
11:124754341	acceptor_loss	1.0000
11:124754764–124754765	acceptor_loss	1.0000	5
11:124754212	donor_loss	0.9900
11:124754341–124754342	acceptor_loss	0.9900	2
11:124754764–124754766	acceptor_loss	0.9900	2
11:124756536	donor_loss	0.9900
11:124756539–124756540	donor_loss	0.9900	6
11:124756743–124756744	acceptor_loss	0.9900	6
11:124756746	acceptor_gain	0.9900

AlphaMissense

413 missense substitutions predicted likely pathogenic (of 2,470 scored), across 139 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
D288	8	0.843	0.935
C224	7	0.985	0.995
C174	7	0.976	0.989
W187	7	0.969	0.999
C158	7	0.963	0.982
C235	7	0.958	0.980
W73	7	0.928	0.990
C126	7	0.911	0.977
N228	7	0.869	0.976
E287	7	0.691	0.786
G207	6	0.919	0.975
S179	6	0.827	0.963
N108	6	0.824	0.927
D203	6	0.671	0.777
Y222	5	0.974	0.989
Y124	5	0.967	0.993
Y185	5	0.947	0.975
Y54	5	0.905	0.962
S110	5	0.865	0.978
V149	5	0.864	0.951

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.17e-07
Kidney Renal Clear Cell Carcinoma (validation)	favorable	1.29e-05

Disease associations

OMIM: gene MIM:614281 | disease phenotypes: MIM:620371

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity	Definitive	Autosomal recessive	4

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (9 panels, 9 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

9 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
White matter disorders and cerebral calcification - childhood onset	green

Mondo (1): neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity (MONDO:0957267)

HPO phenotypes

showing 60 of 93 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000189	Narrow palate
HP:0000218	High palate
HP:0000232	Everted lower lip vermilion
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000293	Full cheeks
HP:0000303	Mandibular prognathia
HP:0000308	Microretrognathia
HP:0000319	Smooth philtrum
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000341	Narrow forehead
HP:0000358	Posteriorly rotated ears
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000476	Cystic hygroma
HP:0000506	Telecanthus
HP:0000527	Long eyelashes
HP:0000541	Retinal detachment
HP:0000573	Retinal hemorrhage
HP:0000582	Upslanted palpebral fissure
HP:0000612	Iris coloboma
HP:0000631	Retinal arterial tortuosity
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000664	Synophrys
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001285	Spastic tetraparesis
HP:0001332	Dystonia
HP:0001342	Cerebral hemorrhage
HP:0001347	Hyperreflexia
HP:0001518	Small for gestational age
HP:0001640	Cardiomegaly
HP:0001655	Patent foramen ovale
HP:0001733	Pancreatitis
HP:0001762	Talipes equinovarus
HP:0001765	Hammertoe
HP:0001789	Hydrops fetalis
HP:0002069	Bilateral tonic-clonic seizure
HP:0002089	Pulmonary hypoplasia
HP:0002093	Respiratory insufficiency
HP:0002126	Polymicrogyria
HP:0002132	Porencephalic cyst
HP:0002135	Basal ganglia calcification
HP:0002170	Intracranial hemorrhage
HP:0002171	Gliosis
HP:0002181	Cerebral edema
HP:0002324	Hydranencephaly
HP:0002421	Poor head control
HP:0002509	Limb hypertonia
HP:0002514	Cerebral calcification
HP:0002521	Hypsarrhythmia
HP:0002540	Inability to walk

GWAS associations

5 associations:

Study	Trait	p-value
GCST006585_2675	Blood protein levels	5e-22
GCST006803_3	Schizophrenia	2e-15
GCST004521_90	Autism spectrum disorder or schizophrenia	5e-13
GCST002539_83	Schizophrenia	3e-12
GCST006585_2986	Blood protein levels	3e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, decreases methylation	4
sodium arsenite	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
kojic acid	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Decitabine	increases expression	1
Aldehydes	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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