HEPN1

protein-coding

hepatocellular carcinoma, down-regulated 1

Gene summary

This gene is expressed predominantly in the liver. Transient transfection studies show the expression of this gene significantly inhibits cell growth, suggesting a role for this gene in apoptosis. Expression of this gene is down-regulated or lost in hepatocellular carcinomas (HCC), suggesting that loss of this gene is involved in carcinogenesis of hepatocytes (PMID:12971969). This gene maps to the 3'-noncoding region of the HEPACAM gene (GeneID:220296) on the antisense strand. [provided by RefSeq, Aug 2020]

MANE transcript

NM_001037558.4

Inheritance

—

ClinVar variants

U:2B:1

Top phenotype

Megalencephalic leukoencephalopathy with subcortical cysts

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chr11:124,919,250-124,920,677

External References & Databases

Ensembl (ENSG00000221932)

Transcript & Mutation Effects

hg38 • Region Span ~1.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HEPN1 variants in ClinVar

2 Conditions Cataloged

Megalencephalic leukoencephalopathy with subcortical cystsTotal: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001037558.4. 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	1 clinvar		2
missense						0
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	2	1	0	3

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001037558.4	RefSeq	NP_001032647.2	1	MANE Select
ENST00000408930.7	Ensembl	ENSP00000386143.4	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000408930
Coding exons: 1
Length: 1428

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.147	45	47.9	0.940	0.00000243	569
Missense (PolyPhen)		10	10.032	0.99681		129
Synonymous	-0.492	22	19.3	1.14	9.14e-7	176
Loss of Function

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.674
RVIS EVS: 0.68
RVIS percentile EVS: 84.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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