ERLN

Summary

ERLN (endoregulin, HGNC:40032) is a protein-coding gene on chromosome 17q25.1, encoding Endoregulin (P0DI80). Inhibits the activity of the calcium ATPases ATP2A2/SERCA2 and ATP2A3/SERCA3 by decreasing their apparent affinity for Ca(2+).

Predicted to act upstream of or within negative regulation of ATPase-coupled calcium transmembrane transporter activity. Predicted to be located in endoplasmic reticulum membrane.

Source: NCBI Gene 100130933 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 6 total
• MANE Select transcript: NM_001162997

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40032
Approved symbol	ERLN
Name	endoregulin
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	ELN
Ensembl gene	ENSG00000259120
Ensembl biotype	protein_coding
OMIM	620531
Entrez	100130933

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000556126, ENST00000579469, ENST00000911162

RefSeq mRNA: 1 — MANE Select: NM_001162997 NM_001162997

CCDS: CCDS54166

Canonical transcript exons

ENST00000579469 — 2 exons

Exon	Start	End
ENSE00002690836	75647371	75647974
ENSE00002718880	75646251	75646786

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 96.42.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6127 / max 85.2959, expressed in 208 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162762	0.2355	97
162760	0.1733	94
162764	0.1028	21
162761	0.0680	28
162763	0.0330	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.42	gold quality
kidney epithelium	UBERON:0004819	91.71	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.65	gold quality
left testis	UBERON:0004533	85.46	gold quality
right testis	UBERON:0004534	84.50	gold quality
ileal mucosa	UBERON:0000331	82.93	gold quality
testis	UBERON:0000473	82.55	gold quality
pancreatic ductal cell	CL:0002079	82.35	silver quality
mucosa of transverse colon	UBERON:0004991	82.27	gold quality
islet of Langerhans	UBERON:0000006	82.25	gold quality
right uterine tube	UBERON:0001302	82.09	gold quality
adult mammalian kidney	UBERON:0000082	81.78	gold quality
gall bladder	UBERON:0002110	80.52	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.69	gold quality
duodenum	UBERON:0002114	79.11	gold quality
jejunal mucosa	UBERON:0000399	78.44	gold quality
spinal cord	UBERON:0002240	77.83	gold quality
bronchial epithelial cell	CL:0002328	77.58	gold quality
kidney	UBERON:0002113	77.41	gold quality
body of stomach	UBERON:0001161	76.69	gold quality
bronchus	UBERON:0002185	76.32	gold quality
pancreas	UBERON:0001264	76.17	gold quality
rectum	UBERON:0001052	75.72	gold quality
epithelial cell of pancreas	CL:0000083	75.64	gold quality
metanephros cortex	UBERON:0010533	75.31	gold quality
cortex of kidney	UBERON:0001225	75.13	gold quality
stomach	UBERON:0000945	75.11	gold quality
colonic mucosa	UBERON:0000317	75.05	gold quality
right lobe of liver	UBERON:0001114	74.28	gold quality
body of pancreas	UBERON:0001150	73.99	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	1387.01
E-MTAB-10287	yes	25.31
E-GEOD-125970	yes	7.12
E-ANND-3	yes	4.50
E-HCAD-31	no	3.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting ERLN, 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-144-3P	99.94	73.98	2698
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-1178-5P	95.83	64.12	504
HSA-MIR-2861	95.24	65.47	1056

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Endoregulin — P0DI80 (reviewed: P0DI80)

Alternative names: Small integral membrane protein 6

All UniProt accessions (1): P0DI80

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits the activity of the calcium ATPases ATP2A2/SERCA2 and ATP2A3/SERCA3 by decreasing their apparent affinity for Ca(2+).

Subunit / interactions. Homooligomer. Can also form heterooligomers with other sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) regulators ARLN, PLN, SLN and STRIT1/DWORF. Monomer. Interacts as a monomer with ATP2A2/SERCA2; the interaction results in inhibition of ATP2A2 Ca(2+) affinity.

Subcellular location. Endoplasmic reticulum membrane.

RefSeq proteins (1): NP_001156469* (*=MANE)

Domains & families (InterPro)

UniProt features (2 total): chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DI80-F1	77.26	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 830 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_MUSCLE_TISSUE_DEVELOPMENT, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, MODULE_45, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_EXTRACELLULAR_MATRIX_ASSEMBLY, GOBP_MUSCLE_CELL_PROLIFERATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERLN	ARLN	Q8WVX3	805
ERLN	STRIT1	P0DN84	729
ERLN	MRLN	P0DMT0	714
ERLN	SLN	O00631	606
ERLN	TBC1D3K	A0A087X1G2	571
ERLN	CDRT15L2	A8MXV6	520
ERLN	TBC1D3H	P0C7X1	479
ERLN	TBC1D28	Q2M2D7	447
ERLN	TBC1D3D	A0A087WVF3	444
ERLN	SLC35G6	P0C7Q6	430
ERLN	SLC35G3	Q8N808	419
ERLN	CCDC144A	A2RUR9	419
ERLN	SMIM5	Q71RC9	418
ERLN	SPDYE4	A6NLX3	404
ERLN	OR3A2	P47893	402

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GQX2, A0A1B0GTB2, A2BUT0, A2C0D2, A6BM34, A7M911, A8W3J7, B0JYB0, B1WS50, B2J4U1, B2Y1W9, B7JV08, B7KFH4, O19926, O29047, O70901, P0C0X9, P0C179, P0DI80, P27387, P29662, P30395, P31591, P58246, Q06GN1, Q06RE7, Q06SD5, Q06SI9, Q110N3, Q1ACL7, Q28053, Q28280, Q28748, Q28757, Q29149, Q32FX5, Q3J1A4, Q3M5W2, Q46H80, Q54YR4

Diamond homologs: P0DI80, Q3U0I6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

186 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75647365:TTCCA:T	acceptor_loss	0.9900
17:75647366:TCCA:T	acceptor_loss	0.9900
17:75647367:CCA:C	acceptor_loss	0.9900
17:75647368:CA:C	acceptor_loss	0.9900
17:75647369:AGA:A	acceptor_loss	0.9900
17:75646367:CACAG:C	donor_loss	0.9800
17:75646368:ACAG:A	donor_loss	0.9800
17:75646369:CAGG:C	donor_loss	0.9800
17:75646370:AGGTG:A	donor_loss	0.9800
17:75646371:GGT:G	donor_loss	0.9800
17:75646372:GTGAG:G	donor_loss	0.9800
17:75646373:T:A	donor_loss	0.9800
17:75646653:A:AG	acceptor_gain	0.9700
17:75646654:G:GG	acceptor_gain	0.9700
17:75647369:A:AG	acceptor_gain	0.9700
17:75647370:G:GG	acceptor_gain	0.9700
17:75646654:GTT:G	acceptor_gain	0.9500
17:75647370:GATT:G	acceptor_gain	0.9500
17:75646782:ATCAG:A	donor_loss	0.9300
17:75646783:TCAGG:T	donor_loss	0.9300
17:75646784:CAG:C	donor_loss	0.9300
17:75646785:AGGT:A	donor_loss	0.9300
17:75646786:GGTAA:G	donor_loss	0.9300
17:75646787:G:T	donor_loss	0.9300
17:75646788:T:A	donor_loss	0.9300
17:75647553:TG:T	donor_gain	0.9200
17:75647370:GA:G	acceptor_gain	0.9100
17:75646653:AGTT:A	acceptor_gain	0.8900
17:75646654:GTTG:G	acceptor_gain	0.8900
17:75646374:G:GT	donor_loss	0.8600

AlphaMissense

403 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75647509:T:C	F45L	0.927
17:75647511:T:A	F45L	0.927
17:75647511:T:G	F45L	0.927
17:75647424:G:C	W16C	0.869
17:75647424:G:T	W16C	0.869
17:75647456:T:A	V27E	0.843
17:75647443:G:A	G23R	0.842
17:75647443:G:C	G23R	0.842
17:75647436:G:C	W20C	0.840
17:75647436:G:T	W20C	0.840
17:75647501:C:A	A42D	0.823
17:75647434:T:A	W20R	0.820
17:75647434:T:C	W20R	0.820
17:75647419:T:C	F15L	0.817
17:75647421:C:A	F15L	0.817
17:75647421:C:G	F15L	0.817
17:75647450:T:C	L25P	0.806
17:75647447:G:A	G24D	0.802
17:75647446:G:C	G24R	0.774
17:75647497:T:C	F41L	0.774
17:75647499:T:A	F41L	0.774
17:75647499:T:G	F41L	0.774
17:75647422:T:A	W16R	0.772
17:75647422:T:C	W16R	0.772
17:75647483:T:G	L36R	0.770
17:75647489:T:G	L38R	0.769
17:75647444:G:A	G23E	0.760
17:75647512:G:C	G46R	0.753
17:75647467:T:C	F31L	0.746
17:75647469:C:A	F31L	0.746

dbSNP variants (sampled 300 via entrez): RS1000140249 (17:75646101 C>A), RS1000740986 (17:75644486 G>C), RS1001122212 (17:75645700 G>A), RS1001236558 (17:75645758 A>G), RS1005564698 (17:75646384 G>A,C), RS1005588108 (17:75647106 C>A,G), RS1005900357 (17:75647894 A>T), RS1006012548 (17:75646838 T>A,C), RS1007046490 (17:75646729 C>T), RS1007057708 (17:75646467 C>G,T), RS1007093534 (17:75645730 G>A), RS1007422382 (17:75647244 G>A), RS1008092852 (17:75644381 A>C,G), RS1008540575 (17:75644601 A>G), RS1009965943 (17:75645692 G>A)

Disease associations

OMIM: gene MIM:620531 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methyleugenol	increases expression	1
sodium arsenite	increases expression	1
abrine	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Ethinyl Estradiol	affects expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Genistein	affects expression	1

Clinical trials (associated diseases)

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