HEPN1

Summary

HEPN1 (hepatocellular carcinoma, down-regulated 1, HGNC:34400) is a protein-coding gene on chromosome 11q24.2, encoding Protein HEPN1 (Q6WQI6).

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.

Source: NCBI Gene 641654 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001037558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34400
Approved symbol	HEPN1
Name	hepatocellular carcinoma, down-regulated 1
Location	11q24.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000221932
Ensembl biotype	protein_coding
OMIM	611641
Entrez	641654

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000408930

RefSeq mRNA: 1 — MANE Select: NM_001037558 NM_001037558

Canonical transcript exons

ENST00000408930 — 1 exons

Exon	Start	End
ENSE00001569097	124919250	124920677

Expression profiles

Bgee: expression breadth ubiquitous, 117 present calls, max score 98.16.

Top tissues by expression

132 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	98.16	gold quality
amygdala	UBERON:0001876	98.11	gold quality
temporal lobe	UBERON:0001871	97.92	gold quality
putamen	UBERON:0001874	97.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.81	gold quality
substantia nigra	UBERON:0002038	97.73	gold quality
caudate nucleus	UBERON:0001873	97.61	gold quality
Ammon’s horn	UBERON:0001954	97.53	gold quality
nucleus accumbens	UBERON:0001882	97.40	gold quality
right frontal lobe	UBERON:0002810	96.29	gold quality
hypothalamus	UBERON:0001898	96.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.64	gold quality
anterior cingulate cortex	UBERON:0009835	95.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.32	gold quality
cerebral cortex	UBERON:0000956	94.34	gold quality
primary visual cortex	UBERON:0002436	93.90	gold quality
frontal cortex	UBERON:0001870	93.64	gold quality
prefrontal cortex	UBERON:0000451	93.28	gold quality
superior frontal gyrus	UBERON:0002661	91.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.24	gold quality
brain	UBERON:0000955	90.01	gold quality
cerebellum	UBERON:0002037	88.51	gold quality
cerebellar hemisphere	UBERON:0002245	88.48	gold quality
cerebellar cortex	UBERON:0002129	88.43	gold quality
ventricular zone	UBERON:0003053	84.08	gold quality
right lobe of liver	UBERON:0001114	81.19	gold quality
tibial nerve	UBERON:0001323	78.76	gold quality
adipose tissue	UBERON:0001013	77.61	gold quality
omental fat pad	UBERON:0010414	77.59	gold quality
subcutaneous adipose tissue	UBERON:0002190	77.51	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	378.07
E-HCAD-25	yes	21.05
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting HEPN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-3976	96.67	67.79	1187

Literature-anchored findings (GeneRIF, showing 2)

• ROS increase production of an alternately spliced form of X-box binding protein 1 (XBP1s) and XBP1s increases HEPN1 expression by binding to the HEPN1 promoter (PMID:25448679)
• the current study suggested an underlying mechanism that miR-21 directly target HEPN1 and inhibit its expression during the carcinogenesis of HCC. HEPN1 may thus be a candidate as a therapeutic target for patients with HCC. (PMID:25687183)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Protein HEPN1 — Q6WQI6 (reviewed: Q6WQI6)

Alternative names: Cancer susceptibility gene HEPN1 protein

All UniProt accessions (1): Q6WQI6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in liver. Expression is either down-regulated or lost in hepatocellular carcinomas (HCC).

Induction. Up-regulated by reactive oxygen species.

Miscellaneous. Encoded on the opposite strand of the 3’-UTR of HEPACAM.

RefSeq proteins (1): NP_001032647* (*=MANE)

Domains & families (InterPro)

UniProt features (2 total): chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6WQI6-F1	54.42	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 14 (showing top): AGGAAGC_MIR5163P, chr11q24, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR7977, MIR6795_5P, MIR6887_5P, MIR3976, MIR5000_5P, MANNO_MIDBRAIN_NEUROTYPES_HOPC, MANNO_MIDBRAIN_NEUROTYPES_HRGL2C, MANNO_MIDBRAIN_NEUROTYPES_HRGL2B, MANNO_MIDBRAIN_NEUROTYPES_HRGL2A, MANNO_MIDBRAIN_NEUROTYPES_HRGL3, GAVISH_3CA_MALIGNANT_METAPROGRAM_25_ASTROCYTES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

436 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HEPN1	ANXA5	P08758	844
HEPN1	HEPACAM	Q14CZ8	324
HEPN1	SPANXN2	Q5MJ10	308
HEPN1	CNTN5	O94779	292
HEPN1	TTC9	Q92623	249
HEPN1	CCDC32	Q9BV29	247
HEPN1	MUCL3	Q3MIW9	243
HEPN1	PRB3	Q04118	224
HEPN1	PSMD14	O00487	220
HEPN1	RWDD3	Q9Y3V2	205
HEPN1	SH3GLB2	Q9NR46	205
HEPN1	ZNF717	Q9BY31	202
HEPN1	DOP1B	Q9Y3R5	200
HEPN1	PTTG1IP	P53801	183
HEPN1	SCUBE3	Q8IX30	179

IntAct

3 interactions, top by confidence:

A	B	Type	Score
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
HEPN1	DUSP14	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): HEPN1 (Affinity Capture-MS), HEPHL1 (Affinity Capture-MS), NEU2 (Affinity Capture-MS), PGK2 (Affinity Capture-MS), LYG2 (Affinity Capture-MS), S100A3 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), DUSP14 (Affinity Capture-MS), DSG4 (Affinity Capture-MS)

ESM2 similar proteins: A0A023PXH5, B2T7U2, B7GPF6, C0H400, K7LFJ0, O29001, O83082, O83168, O83199, O83253, O83260, O83302, O83304, O83305, O83352, O83480, O83616, O83697, O83793, O83839, O83910, O83916, O83936, P03084, P03782, P0AD83, P0AD84, P0AD85, P10396, P14505, P15973, P49168, Q05381, Q05BU3, Q13SH3, Q2Y5A7, Q30YQ4, Q3V4R1, Q46403, Q5VT28

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

186 predictions. Top by Δscore:

Variant	Effect	Δscore
11:124920524:G:T	acceptor_gain	0.7200
11:124919633:G:GT	donor_gain	0.7000
11:124920022:G:GT	donor_gain	0.6900
11:124920522:TAG:T	acceptor_gain	0.6900
11:124920523:AGG:A	acceptor_gain	0.6900
11:124919308:A:AG	donor_gain	0.6600
11:124919586:G:T	donor_gain	0.6400
11:124919633:G:T	donor_gain	0.6400
11:124919276:G:GG	donor_gain	0.6200
11:124919664:C:T	donor_gain	0.6200
11:124920627:GCTTA:G	acceptor_gain	0.6100
11:124919650:G:GT	donor_gain	0.5900
11:124919275:A:AG	donor_gain	0.5700
11:124919434:GG:G	donor_gain	0.5600
11:124919435:GG:G	donor_gain	0.5600
11:124920191:G:GT	donor_gain	0.5400
11:124920246:G:GT	donor_gain	0.5200
11:124919586:G:GT	donor_gain	0.4900
11:124920007:T:G	donor_gain	0.4900
11:124919305:G:GG	donor_gain	0.4800
11:124919304:A:AG	donor_gain	0.4700
11:124920010:T:A	donor_gain	0.4700
11:124920008:G:GG	donor_gain	0.4400
11:124920520:TGTAG:T	acceptor_gain	0.4400
11:124920521:GTAGG:G	acceptor_gain	0.4400
11:124920160:TGGAG:T	acceptor_gain	0.4300
11:124920241:G:GG	donor_gain	0.4300
11:124920378:GA:G	acceptor_gain	0.4300
11:124919322:A:G	donor_gain	0.4100
11:124920162:G:C	acceptor_gain	0.4100

AlphaMissense

572 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:124919886:T:C	F46L	0.716
11:124919888:C:A	F46L	0.716
11:124919888:C:G	F46L	0.716
11:124919892:T:C	F48L	0.629
11:124919894:T:A	F48L	0.629
11:124919894:T:G	F48L	0.629
11:124919880:T:C	F44L	0.612
11:124919882:C:A	F44L	0.612
11:124919882:C:G	F44L	0.612
11:124919946:T:C	F66L	0.592
11:124919948:C:A	F66L	0.592
11:124919948:C:G	F66L	0.592

dbSNP variants (sampled 300 via entrez): RS1000899669 (11:124919743 TGGA>T), RS1001543144 (11:124919418 C>T), RS1002006325 (11:124920847 G>A,C), RS1002307424 (11:124917972 G>A), RS1002625486 (11:124919040 T>C,G), RS1003086004 (11:124918760 C>A,T), RS1004636554 (11:124919581 C>G,T), RS1005454450 (11:124920372 T>C), RS1006494935 (11:124918501 C>G,T), RS1008507428 (11:124920875 T>C), RS1008819052 (11:124920296 G>C,T), RS1009547380 (11:124919008 T>A), RS1010205596 (11:124920758 A>G), RS1011207283 (11:124918978 C>A,T), RS1011346525 (11:124918749 T>A,C,G)

Disease associations

OMIM: gene MIM:611641 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): megalencephalic leukoencephalopathy with subcortical cysts (MONDO:0011391)

Orphanet (1): Megalencephalic leukoencephalopathy with subcortical cysts (Orphanet:2478)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002861_2	Breast cancer (survival)	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0000714	survival time

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536141	Megalencephalic leukoencephalopathy with subcortical cysts (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Copper	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project