JAM3

junctional adhesion molecule 3, the group of V-set domain containing|Ig-like cell adhesion molecule family|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 11:134069071-134152001

Links

ENSG00000166086 ∙ NCBI:83700 ∙ OMIM:606871 ∙ HGNC:15532 ∙ Uniprot:Q9BX67 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• porencephaly-microcephaly-bilateral congenital cataract syndrome (Strong), mode of inheritance: AR
• porencephaly-microcephaly-bilateral congenital cataract syndrome (Strong), mode of inheritance: AR
• porencephaly-microcephaly-bilateral congenital cataract syndrome (Strong), mode of inheritance: AR
• porencephaly-microcephaly-bilateral congenital cataract syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemorrhagic destruction of the brain, subependymal calcification, and cataracts	AR	General	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	Cardiovascular; Neurologic; Ophthalmologic; Renal	21109224; 23255084

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the JAM3 gene.

• Porencephaly-microcephaly-bilateral congenital cataract syndrome (6 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the JAM3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	21	2	24
missense	1	1	55	4	1	62
nonsense	1		1			2
start loss	1	1				2
frameshift	4	1				5
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2					2
splice region			5	8	3	16
non coding		1	2	32	29	64
Total	9	4	61	57	32

Highest pathogenic variant AF is 0.0000197

Variants in JAM3

This is a list of pathogenic ClinVar variants found in the JAM3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-134069076-C-T			Likely benign (Sep 18, 2018)
11-134069084-A-G		Porencephaly-microcephaly-bilateral congenital cataract syndrome	Pathogenic (Jun 06, 2019)
11-134069085-T-A		Porencephaly-microcephaly-bilateral congenital cataract syndrome	Likely pathogenic (Feb 05, 2020)
11-134069085-T-G		Porencephaly-microcephaly-bilateral congenital cataract syndrome	Pathogenic (Mar 01, 2013)
11-134069087-G-T		Inborn genetic diseases	Uncertain significance (Jan 15, 2024)
11-134069097-G-A			Uncertain significance (Dec 11, 2023)
11-134069106-G-A			Uncertain significance (May 03, 2022)
11-134069123-C-T			Uncertain significance (Aug 09, 2022)
11-134069126-C-G			Likely benign (Jan 15, 2024)
11-134069164-G-T		Inborn genetic diseases	Uncertain significance (Jan 28, 2022)
11-134069360-C-T			Likely benign (Dec 01, 2018)
11-134069412-C-T			Benign (Jul 31, 2018)
11-134094614-CTTCTCCTGAACCCTCCTTATTCATCATGTTCCACCTTAAATGTCACTTCCTGAGGGAAGCAT-C		Schizophrenia	Uncertain significance (Nov 11, 2022)
11-134139806-G-A			Likely benign (Dec 01, 2018)
11-134139834-T-C			Likely benign (Feb 22, 2023)
11-134139842-C-G			Likely benign (Oct 03, 2023)
11-134139887-A-G		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
11-134139890-G-A			Uncertain significance (May 12, 2022)
11-134139891-A-T			Likely benign (Aug 16, 2022)
11-134139914-AAAGT-A			Uncertain significance (Dec 15, 2021)
11-134139919-A-G			Uncertain significance (Jan 03, 2022)
11-134139928-C-T			Likely benign (Nov 27, 2023)
11-134139965-T-C			Benign (Jun 29, 2018)
11-134140005-TA-T			Benign (Jul 22, 2021)
11-134140052-G-A			Benign (Jun 06, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
JAM3	protein_coding	protein_coding	ENST00000299106	9	83077

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000616	0.979	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.867	205	173	1.19	0.0000108	2013
Missense in Polyphen		54	63.581	0.84931		747
Synonymous	-1.54	84	67.8	1.24	0.00000434	618
Loss of Function	2.04	8	17.1	0.467	8.62e-7	200

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000251	0.000242
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000968	0.0000967
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates cell-cell adhesion (PubMed:11590146, PubMed:12208882, PubMed:15194813). Functions as counter-receptor for JAM2 (PubMed:11590146). Functions as a counter-receptor for ITGAM, mediating leukocyte-platelet interactions and is involved in the regulation of transepithelial migration of polymorphonuclear neutrophils (PMN) (PubMed:12208882, PubMed:15194813). Plays a role in angiogenesis (PubMed:23255084). May play a role in the regulation of cell migration (Probable). Required for normal polarization and acrosome formation in developing spermatids, and for normal male fertility (By similarity). {ECO:0000250|UniProtKB:Q9D8B7, ECO:0000269|PubMed:11590146, ECO:0000269|PubMed:12208882, ECO:0000269|PubMed:15194813, ECO:0000269|PubMed:23255084, ECO:0000305|PubMed:28196865}.
• Disease: DISEASE: Hemorrhagic destruction of the brain with subependymal calcification and cataracts (HDBSCC) [MIM:613730]: A syndrome characterized by congenital cataracts and severe brain abnormalities apparently resulting from hemorrhagic destruction of the brain parenchyma, including the cerebral white matter and basal ganglia. Patients manifest profound developmental delay, and other neurologic features included seizures, spasticity, and hyperreflexia. The clinical course is very severe resulting in death in infancy. Brain imaging shows multifocal intraparenchymal hemorrhage with associated liquefaction and massive cystic degeneration, and calcification in the subependymal region and in brain tissue. {ECO:0000269|PubMed:21109224, ECO:0000269|PubMed:23255084}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Tight junction - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Integrin cell surface interactions;Extracellular matrix organization;Cell surface interactions at the vascular wall;Hemostasis;amb2 Integrin signaling;Beta2 integrin cell surface interactions (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.691
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.27

Haploinsufficiency Scores

• pHI: 0.131
• hipred: Y
• hipred_score: 0.501
• ghis: 0.503

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.637

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Jam3
• Phenotype: digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; reproductive system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: jam3b
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: mononucleate

Gene ontology

• Biological process: angiogenesis;neutrophil homeostasis;adaptive immune response;myeloid progenitor cell differentiation;leukocyte migration involved in inflammatory response;cell-matrix adhesion;spermatid development;transmission of nerve impulse;establishment of cell polarity;extracellular matrix organization;axon regeneration;myelination;leukocyte migration;regulation of neutrophil chemotaxis;regulation of actin cytoskeleton organization by cell-cell adhesion
• Cellular component: extracellular space;Golgi apparatus;plasma membrane;integral component of plasma membrane;bicellular tight junction;desmosome;paranodal junction;Schmidt-Lanterman incisure;cell-cell contact zone
• Molecular function: integrin binding;protein binding;protein homodimerization activity;protein heterodimerization activity