ESAM

protein-coding

endothelial cell adhesion molecule, the group of V-set domain containing|IgCAM CXADR-related subfamily

Gene summary

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. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_138961.3

Inheritance

AR, AD

ClinVar variants

P:8U:63B:13

Top phenotype

Schizophrenia; Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr11:124,752,583-124,762,290

External References & Databases

Ensembl (ENSG00000149564)

Transcript & Mutation Effects

hg38 • Region Span ~9.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticityDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0957267

Submitter: Ambry Genetics

neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticitySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957267

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957267

Submitter: G2P

neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticitySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957267

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Schizophrenia; Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticityAD/AR

Manifestation: Craniofacial; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 21822266; 36996813,

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ESAM variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 68

not providedTotal: 12

Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticityTotal: 8

See casesTotal: 4

ESAM-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138961.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	7 clinvar		8
missense			62 clinvar	6 clinvar		68
nonsense		3 clinvar				3
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar				3
Total	1	7	63	13	0	84

Highest pathogenic variant AF is 0.000013154433

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138961.3	RefSeq	NP_620411.2	7	MANE Select
ENST00000278927.10	Ensembl	ENSP00000278927.5	7	MANE Select
ENST00000417453.5	Ensembl	ENSP00000389235.1	5	Standard
ENST00000435477.1	Ensembl	ENSP00000415893.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
esama	Danio rerio	Structure: thrombocyte Quality: aggregated abnormal

Gene / Model

Organism

Observed Phenotype

esama

Danio rerio

Structure: thrombocyte

Quality: aggregated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Leukocyte transendothelial migration - Homo sapiens (human)
Cell surface interactions at the vascular wall
Hemostasis

Biological Process

homophilic cell adhesion via plasma membrane adhesion molecules
leukocyte migration

Cellular Component

plasma membrane
adherens junction
bicellular tight junction
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000278927
Coding exons: 7
Length: 10161
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.461	238	219	1.09	0.0000113	2450
Missense (PolyPhen)		54	60.528	0.89214		723
Synonymous	0.224	91	93.8	0.971	0.00000463	884
Loss of Function	2.71	4	15.5	0.258	7.59e-7	176

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00029	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Can mediate aggregation most likely through a homophilic molecular interaction. {ECO:0000250}.;

Recessive Scores

pRec: 0.166

Intolerance Scores

LoFtool: 0.486
RVIS EVS: 0.2
RVIS percentile EVS: 67.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.494

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium