HEPACAM

hepatic and glial cell adhesion molecule, the group of V-set domain containing|Ig-like cell adhesion molecule family

Basic information

Region (hg38): 11:124919205-124936412

Links

ENSG00000165478 ∙ NCBI:220296 ∙ OMIM:611642 ∙ HGNC:26361 ∙ Uniprot:Q14CZ8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• megalencephalic leukoencephalopathy with subcortical cysts 2A (Strong), mode of inheritance: AR
• megalencephalic leukoencephalopathy with subcortical cysts (Supportive), mode of inheritance: AD
• macrocephaly-autism syndrome (Supportive), mode of inheritance: AD
• megalencephalic leukoencephalopathy with subcortical cysts 2A (Strong), mode of inheritance: AR
• megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability (Strong), mode of inheritance: AD
• megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability (Moderate), mode of inheritance: AD
• megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability (Definitive), mode of inheritance: AD
• megalencephalic leukoencephalopathy with subcortical cysts 2A (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without impaired intellectual development; Megalencephalic leukoencephalopathy with subcortical cysts 2A	AD/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	Neurologic	20517947; 21419380

ClinVar

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

• not_provided (195 variants)
• Inborn_genetic_diseases (50 variants)
• Megalencephalic_leukoencephalopathy_with_subcortical_cysts (29 variants)
• Megalencephalic_leukoencephalopathy_with_subcortical_cysts_2A (25 variants)
• HEPACAM-related_disorder (17 variants)
• Megalencephalic_leukoencephalopathy_with_subcortical_cysts_2B,_remitting,_with_or_without_intellectual_disability (17 variants)
• not_specified (10 variants)
• Megalencephalic_leukoencephalopathy_with_subcortical_cysts_1 (8 variants)
• Intellectual_disability (2 variants)
• Autism_spectrum_disorder (1 variants)
• MEGALENCEPHALIC_LEUKOENCEPHALOPATHY_WITH_SUBCORTICAL_CYSTS_2B,_REMITTING,_WITH_IMPAIRED_INTELLECTUAL_DEVELOPMENT (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HEPACAM gene is commonly pathogenic or not. These statistics are base on transcript: NM_000152722.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	41	1	44
missense	3	7	123	14	2	149
nonsense	3	1				4
start loss						0
frameshift	4	1				5
splice donor/acceptor (+/-2bp)		3				3
Total	10	12	125	55	3

Highest pathogenic variant AF is 0.0000168204

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HEPACAM	protein_coding	protein_coding	ENST00000298251	7	17220

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.868	0.132	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.59	145	210	0.691	0.0000126	2619
Missense in Polyphen		55	84.066	0.65425		936
Synonymous	0.189	89	91.3	0.975	0.00000560	899
Loss of Function	3.16	2	15.4	0.130	8.99e-7	183

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00125	0.00125
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00125	0.00125
South Asian	0.00	0.00
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in regulating cell motility and cell-matrix interactions. May inhibit cell growth through suppression of cell proliferation. {ECO:0000269|PubMed:15885354, ECO:0000269|PubMed:15917256}.
• Disease: DISEASE: Leukoencephalopathy, megalencephalic, with subcortical cysts, 2A (MLC2A) [MIM:613925]: A neurodegenerative disorder characterized by infantile-onset macrocephaly and later onset of motor deterioration, with ataxia and spasticity, seizures, and cognitive decline of variable severity. The brain appears swollen on magnetic resonance imaging with white-matter abnormalities and subcortical cysts, in all stages of the disease. {ECO:0000269|PubMed:21419380}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leukoencephalopathy, megalencephalic, with subcortical cysts, 2B (MLC2B) [MIM:613926]: A neurodegenerative disorder characterized by infantile-onset of macrocephaly and mildly delayed motor development associated with white-matter abnormalities on brain magnetic resonance imaging. The phenotype is milder that MLC2A, with better preserved cerebellar white matter and no subcortical cysts outside the temporal region. On follow-up, patients show normal or almost normal motor function. Some patients have normal intelligence, whereas others have a significant cognitive deficiency. {ECO:0000269|PubMed:21419380}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.115

Intolerance Scores

• loftool: 0.162
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.91

Haploinsufficiency Scores

• pHI: 0.469
• hipred: Y
• hipred_score: 0.630
• ghis: 0.519

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.247

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hepacam
• 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)

Gene ontology

• Biological process: cell cycle arrest;cell adhesion;cellular protein localization;regulation of growth
• Cellular component: cytoplasm;cell-cell junction;integral component of membrane;axon