ARLN

Summary

ARLN (allregulin, HGNC:19225) is a protein-coding gene on chromosome 4q26, encoding Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator ARLN (Q8WVX3). 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 401152 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 10 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001001701

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19225
Approved symbol	ARLN
Name	allregulin
Location	4q26
Locus type	gene with protein product
Status	Approved
Aliases	HCVFTP1, ALN
Ensembl gene	ENSG00000164096
Ensembl biotype	protein_coding
OMIM	620530
Entrez	401152

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000399075, ENST00000504110, ENST00000909938, ENST00000926551

RefSeq mRNA: 2 — MANE Select: NM_001001701 NM_001001701, NM_001170330

CCDS: CCDS43266, CCDS54798

Canonical transcript exons

ENST00000504110 — 2 exons

Exon	Start	End
ENSE00001536323	119300336	119300645
ENSE00003759981	119296419	119298779

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 146.4558 / max 1325.1668, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53752	141.6223	1823
53753	4.8336	1602

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.70	gold quality
upper arm skin	UBERON:0004263	99.54	gold quality
inferior vagus X ganglion	UBERON:0005363	99.43	gold quality
medulla oblongata	UBERON:0001896	99.37	gold quality
superior vestibular nucleus	UBERON:0007227	99.37	gold quality
pons	UBERON:0000988	99.36	gold quality
subthalamic nucleus	UBERON:0001906	99.36	gold quality
saphenous vein	UBERON:0007318	99.32	gold quality
penis	UBERON:0000989	99.30	gold quality
urethra	UBERON:0000057	99.27	gold quality
ileal mucosa	UBERON:0000331	99.27	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.26	gold quality
layer of synovial tissue	UBERON:0007616	99.26	gold quality
kidney epithelium	UBERON:0004819	99.25	gold quality
lateral globus pallidus	UBERON:0002476	99.24	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.23	gold quality
ventral tegmental area	UBERON:0002691	99.21	gold quality
vena cava	UBERON:0004087	99.17	gold quality
epithelial cell of pancreas	CL:0000083	99.16	gold quality
palpebral conjunctiva	UBERON:0001812	99.16	gold quality
synovial joint	UBERON:0002217	99.16	gold quality
oral cavity	UBERON:0000167	99.14	gold quality
germinal epithelium of ovary	UBERON:0001304	99.10	gold quality
globus pallidus	UBERON:0001875	99.07	gold quality
pericardium	UBERON:0002407	99.04	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.04	gold quality
skin of hip	UBERON:0001554	99.01	gold quality
medial globus pallidus	UBERON:0002477	99.01	gold quality
pharyngeal mucosa	UBERON:0000355	99.00	gold quality
trigeminal ganglion	UBERON:0001675	98.98	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	1891.69
E-HCAD-13	yes	11.69
E-MTAB-6819	no	814.10
E-CURD-10	no	748.87
E-MTAB-6524	no	563.89
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting ARLN, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-488-3P	99.61	68.79	1731

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arln	ENSMUSG00000054091
rattus_norvegicus	C2h4orf3	ENSRNOG00000014654

Protein

Protein identifiers

Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator ARLN — Q8WVX3 (reviewed: Q8WVX3)

Alternative names: Allregulin, Another-regulin, Hepatitis C virus F protein-transactivated protein 1

All UniProt accessions (1): Q8WVX3

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 ERLN, 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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WVX3-1	1	yes
Q8WVX3-2	2

RefSeq proteins (2): NP_001001701, NP_001163801 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038780	ALN	Family

Pfam: PF17696

UniProt features (8 total): sequence variant 2, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVX3-F1	68.78	0.30

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 86 (showing top): CLAUS_PGR_POSITIVE_MENINGIOMA_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MENSE_HYPOXIA_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOLDRATH_ANTIGEN_RESPONSE, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, MARTINEZ_RB1_TARGETS_UP, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, MAYBURD_RESPONSE_TO_L663536_DN, MARTINEZ_RB1_AND_TP53_TARGETS_UP, BERENJENO_TRANSFORMED_BY_RHOA_UP, SENESE_HDAC3_TARGETS_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

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
binding	1
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

190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARLN	ERLN	P0DI80	805
ARLN	STRIT1	P0DN84	684
ARLN	MRLN	P0DMT0	677
ARLN	SLN	O00631	587
ARLN	FAM162A	Q96A26	446
ARLN	CFAP96	A7E2U8	396
ARLN	C14orf93	Q9H972	371
ARLN	TCAF2	A6NFQ2	370
ARLN	NBDY	A0A0U1RRE5	348
ARLN	KLHL2	O95198	323
ARLN	ANKRD37	Q7Z713	322
ARLN	CYREN	Q9BWK5	321
ARLN	GNG5	P30670	306
ARLN	HECTD4	Q9Y4D8	270
ARLN	MTLN	Q8NCU8	254

IntAct

11 interactions, top by confidence:

A	B	Type	Score
ARLN	DEGS1	psi-mi:“MI:0914”(association)	0.530
ARLN	HTR2C	psi-mi:“MI:0915”(physical association)	0.370
ARLN	C5AR2	psi-mi:“MI:0915”(physical association)	0.370
ARLN	SMO	psi-mi:“MI:0915”(physical association)	0.370
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
ARLN	PDLIM1	psi-mi:“MI:0914”(association)	0.350
SLC19A3	SNAP23	psi-mi:“MI:0914”(association)	0.350
ARLN	purL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (105): GCN1L1 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), EDC4 (Affinity Capture-MS), DEGS1 (Affinity Capture-MS), ERMP1 (Affinity Capture-MS), CALM1 (Two-hybrid), C4orf3 (PCA), PANX1 (Affinity Capture-MS), DEGS1 (Affinity Capture-MS), EDC4 (Affinity Capture-MS), ERMP1 (Affinity Capture-MS), GCN1L1 (Affinity Capture-MS), C4orf3 (Two-hybrid), C4orf3 (Two-hybrid), C4orf3 (Two-hybrid)

ESM2 similar proteins: A4IHD1, B9VXI8, E1B7R9, F5HGC2, F5HHT4, F7V995, O78514, P03085, P0C733, P0DON5, P0DON6, P0DP88, P0DQF3, P11888, P16722, P16765, P25132, P36704, P89035, Q00LT2, Q00LT9, Q06FN9, Q0Q043, Q16517, Q1HVB5, Q3ZBS9, Q498U0, Q52993, Q5BIS3, Q5R4B0, Q5RDD6, Q5ZKB1, Q61979, Q62649, Q66KZ1, Q6JL78, Q7U9P9, Q8AZJ3, Q8BHL7, Q8NCQ3

Diamond homologs: Q498U0, Q5R4B0, Q8WVX3, Q99M08

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	4
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
149894	GRCh38/hg38 4q26-27(chr4:118360303-120924156)x1	Pathogenic
4057271	Single allele	Likely pathogenic

SpliceAI

268 predictions. Top by Δscore:

Variant	Effect	Δscore
4:119300682:CT:C	donor_gain	0.9900
4:119300673:CTGA:C	donor_gain	0.9800
4:119300681:A:AC	donor_gain	0.9800
4:119300682:C:CC	donor_gain	0.9800
4:119300364:C:CT	donor_gain	0.9700
4:119298775:CAAGT:C	acceptor_gain	0.9600
4:119298780:C:CC	acceptor_gain	0.9500
4:119300365:C:CT	donor_gain	0.9500
4:119300581:AAGTT:A	donor_gain	0.9500
4:119300328:ATACT:A	donor_loss	0.9300
4:119300330:ACT:A	donor_loss	0.9300
4:119300333:C:CC	donor_loss	0.9300
4:119300334:ACC:A	donor_loss	0.9300
4:119300335:C:A	donor_loss	0.9300
4:119300329:TACTC:T	donor_loss	0.9200
4:119300334:A:AC	donor_gain	0.9200
4:119300335:C:CC	donor_gain	0.9200
4:119300335:CCAT:C	donor_gain	0.9000
4:119300334:AC:A	donor_gain	0.8600
4:119300335:CC:C	donor_gain	0.8600
4:119300335:CCATG:C	donor_gain	0.8500
4:119300672:TCTG:T	donor_gain	0.8500
4:119300687:C:A	donor_gain	0.8400
4:119300335:CCA:C	donor_gain	0.8300
4:119298778:GT:G	acceptor_gain	0.8100
4:119300686:T:TA	donor_gain	0.8100
4:119300784:A:AC	donor_gain	0.7700
4:119300785:C:CC	donor_gain	0.7700
4:119300785:CTT:C	donor_gain	0.7500
4:119300787:T:TA	donor_gain	0.7500

AlphaMissense

428 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:119300383:G:C	F51L	0.947
4:119300383:G:T	F51L	0.947
4:119300385:A:G	F51L	0.947
4:119300391:A:G	W49R	0.935
4:119300391:A:T	W49R	0.935
4:119300359:A:C	F59L	0.919
4:119300359:A:T	F59L	0.919
4:119300361:A:G	F59L	0.919
4:119300395:G:C	D47E	0.905
4:119300395:G:T	D47E	0.905
4:119300384:A:G	F51S	0.902
4:119300360:A:G	F59S	0.893
4:119300363:A:T	V58E	0.871
4:119300349:A:C	Y63D	0.868
4:119300371:A:C	D55E	0.866
4:119300371:A:T	D55E	0.866
4:119300396:T:G	D47A	0.855
4:119300403:A:G	W45R	0.855
4:119300403:A:T	W45R	0.855
4:119300384:A:C	F51C	0.847
4:119300396:T:A	D47V	0.844
4:119300385:A:T	F51I	0.841
4:119300393:A:T	L48H	0.840
4:119300349:A:G	Y63H	0.833
4:119300396:T:C	D47G	0.825
4:119300378:A:T	L53H	0.820
4:119300387:A:T	L50H	0.820
4:119300397:C:T	D47N	0.820
4:119300378:A:C	L53R	0.804
4:119300360:A:C	F59C	0.797

dbSNP variants (sampled 300 via entrez): RS1000078952 (4:119302298 G>A), RS1000256127 (4:119302693 A>G), RS1000757799 (4:119303457 A>C,G), RS1000839948 (4:119303083 A>G), RS1001068482 (4:119303686 C>T), RS1001762349 (4:119301065 A>G), RS1001821173 (4:119296565 C>T), RS1002362004 (4:119302667 A>G), RS1002379157 (4:119303021 C>G), RS1002435430 (4:119297907 T>C), RS1003435362 (4:119299493 T>C), RS1003512244 (4:119300805 A>C,T), RS1003598287 (4:119306276 G>T), RS1003650640 (4:119301285 G>A,T), RS1003864893 (4:119299408 G>A)

Disease associations

OMIM: gene MIM:620530 | disease phenotypes: MIM:619658

GenCC curated gene-disease

Mondo (1): cholestasis, progressive familial intrahepatic, 7, with or without hearing loss (MONDO:0030503)

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

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
Oxygen	increases expression	3
Valproic Acid	affects expression, increases expression	3
Cyclosporine	decreases expression	3
Air Pollutants	decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects expression	1
dimethylselenide	decreases expression, increases expression, increases oxidation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
resorcinol	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
Bortezomib	decreases expression	1
Rosiglitazone	decreases expression	1
Temozolomide	decreases expression	1
Cidofovir	decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Coumestrol	decreases expression	1
Doxorubicin	increases expression	1
Ifosfamide	decreases expression	1
Lead	increases expression	1
Quercetin	decreases expression	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

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