ERP27

Summary

ERP27 (endoplasmic reticulum protein 27, HGNC:26495) is a protein-coding gene on chromosome 12p12.3, encoding Endoplasmic reticulum resident protein 27 (Q96DN0). Specifically binds unfolded proteins and may recruit protein disulfide isomerase PDIA3 to unfolded substrates.

This gene encodes a noncatalytic member of the protein disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins. The canonical protein has an N-terminal signal sequence, two thioredoxin (TRX)-like domains and a C-terminal ER-retention sequence. Alternative splicing results in multiple transcript variants encoding distinct isoforms; some of which lack domains present in the canonical protein.

Source: NCBI Gene 121506 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_152321

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26495
Approved symbol	ERP27
Name	endoplasmic reticulum protein 27
Location	12p12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32115, PDIA8
Ensembl gene	ENSG00000139055
Ensembl biotype	protein_coding
OMIM	610642
Entrez	121506

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000266397, ENST00000540097, ENST00000544881

RefSeq mRNA: 2 — MANE Select: NM_152321 NM_001300784, NM_152321

CCDS: CCDS73450, CCDS8670

Canonical transcript exons

ENST00000266397 — 7 exons

Exon	Start	End
ENSE00000936299	14938415	14938537
ENSE00000936300	14937952	14938052
ENSE00000936301	14934856	14934993
ENSE00000936302	14920932	14921048
ENSE00000936309	14917178	14917303
ENSE00000936310	14915489	14915686
ENSE00001100133	14914039	14914782

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 99.40.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9011 / max 1394.0271, expressed in 251 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129890	1.1204	41
129880	0.5626	193
129876	0.0620	24
129879	0.0437	16
129872	0.0356	8
129878	0.0284	9
129873	0.0201	8
129877	0.0120	5
129874	0.0116	6
129875	0.0047	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.40	gold quality
kidney epithelium	UBERON:0004819	97.23	gold quality
epithelial cell of pancreas	CL:0000083	95.11	gold quality
right uterine tube	UBERON:0001302	93.48	gold quality
pancreas	UBERON:0001264	93.17	gold quality
oviduct epithelium	UBERON:0004804	92.55	gold quality
adult mammalian kidney	UBERON:0000082	89.83	gold quality
metanephros cortex	UBERON:0010533	88.38	gold quality
fallopian tube	UBERON:0003889	88.11	gold quality
kidney	UBERON:0002113	87.11	gold quality
metanephros	UBERON:0000081	84.78	gold quality
tibialis anterior	UBERON:0001385	84.14	gold quality
cortex of kidney	UBERON:0001225	83.70	gold quality
islet of Langerhans	UBERON:0000006	81.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.54	gold quality
ileal mucosa	UBERON:0000331	80.86	gold quality
urinary bladder	UBERON:0001255	80.29	gold quality
granulocyte	CL:0000094	79.86	gold quality
right lobe of thyroid gland	UBERON:0001119	78.08	gold quality
blood	UBERON:0000178	77.89	gold quality
renal medulla	UBERON:0000362	77.05	gold quality
germinal epithelium of ovary	UBERON:0001304	76.94	gold quality
leukocyte	CL:0000738	76.79	gold quality
right lung	UBERON:0002167	76.74	gold quality
monocyte	CL:0000576	76.69	gold quality
left lobe of thyroid gland	UBERON:0001120	76.34	gold quality
thyroid gland	UBERON:0002046	76.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	75.24	gold quality
left ventricle myocardium	UBERON:0006566	74.84	gold quality
upper lobe of left lung	UBERON:0008952	74.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	1866.04
E-GEOD-114530	yes	405.37
E-MTAB-5061	yes	18.47
E-MTAB-9388	yes	7.40
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting ERP27, 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-6867-5P	100.00	82.21	3464
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-657	99.48	66.02	848
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-127-5P	97.78	67.64	869
HSA-MIR-890	97.47	68.67	982
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-12128	96.67	66.98	1471
HSA-MIR-6866-5P	96.64	68.06	624

Literature-anchored findings (GeneRIF, showing 3)

• ERp27 is bound by ERp57 both in vitro and in vivo by a similar mechanism by which ERp57 binds calreticulin (PMID:16940051)
• ERp27 is able to distinguish between folded and unfolded substrates, only interacting with the latter and presenting them to for catalysis. (PMID:23192347)
• High-resolution NMR studies of structure and dynamics of human ERp27 indicate extensive interdomain flexibility (PMID:23234573)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Erp27	ENSMUSG00000030219
rattus_norvegicus	Erp27	ENSRNOG00000005787
drosophila_melanogaster	ERp60	FBGN0033663
drosophila_melanogaster	Tmx3	FBGN0036579
drosophila_melanogaster	Pdi	FBGN0286818
caenorhabditis_elegans		WBGENE00003962
caenorhabditis_elegans		WBGENE00003963
caenorhabditis_elegans	pdi-3	WBGENE00003964
caenorhabditis_elegans	M04D5.1	WBGENE00014807
caenorhabditis_elegans	ZK973.11	WBGENE00022836

Paralogs (13): ERP44 (ENSG00000023318), PDIA5 (ENSG00000065485), TMX4 (ENSG00000125827), TMX1 (ENSG00000139921), PDIA6 (ENSG00000143870), TXNDC11 (ENSG00000153066), PDIA4 (ENSG00000155660), TMX3 (ENSG00000166479), PDIA3 (ENSG00000167004), PDILT (ENSG00000169340), PDIA2 (ENSG00000185615), P4HB (ENSG00000185624), TXNDC5 (ENSG00000239264)

Protein

Protein identifiers

Endoplasmic reticulum resident protein 27 — Q96DN0 (reviewed: Q96DN0)

Alternative names: Inactive protein disulfide-isomerase 27

All UniProt accessions (2): Q96DN0, F5GYS6

UniProt curated annotations — full annotation on UniProt →

Function. Specifically binds unfolded proteins and may recruit protein disulfide isomerase PDIA3 to unfolded substrates. Binds protein substrates via a hydrophobic pocket in the C-terminal domain. May play a role in the unfolded stress response.

Subunit / interactions. Interacts with PDIA3.

Subcellular location. Endoplasmic reticulum lumen.

Induction. Induced by ER stress.

Similarity. Belongs to the protein disulfide isomerase family.

RefSeq proteins (2): NP_001287713, NP_689534* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF13848

Enzyme classification (BRENDA):

• EC 5.3.4.1 — protein disulfide-isomerase (BRENDA: 81 organisms, 481 substrates, 347 inhibitors, 35 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

15 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CYSTEINE	1–3	3
MYCOTHIOL-COUPLED HYDROXYETHYL DISULFIDE	0.46–33.69	3
RIBONUCLEASE	0.002–0.01	3
RNASE A	0.007–0.05	3
2-MERCAPTOETHANOL	0.2–0.8	2
DITHIOTHREITOL	0.003–0.0054	2
GSH	5–17	2
RNASE	0.028–0.063	2
SCRAMBLED RIBONUCLEASE	0.0011–0.0033	2
DENATURED-REDUCED LYSOZYME	0.0253	1
INSULIN	2.026	1
INSULIN-(SS)	0.005	1
SCRAMBLED REOXIDIZED LYSOZYME	0.0116	1
SCRAMBLED RNASE	0.02	1
SRNASE	—	0

UniProt features (36 total): helix 11, strand 9, mutagenesis site 6, turn 3, signal peptide 1, chain 1, domain 1, region of interest 1, short sequence motif 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4F9Z	X-RAY DIFFRACTION	2.2
2L4C	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DN0-F1	86.76	0.79

Functional residue map

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

Glycosylation sites (1): 100

Mutagenesis-validated functional residues (6):

Position	Phenotype
231	greatly reduces pdia3 binding in vivo and in vitro.
232	greatly reduces pdia3 binding in vivo and in vitro.
233	greatly reduces pdia3 binding in vivo and in vitro.
168	decreases somatostatin-14 binding.
196	decreases somatostatin-14 binding.
196	conserved pdia3 binding in vivo and in vitro.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GCANCTGNY_MYOD_Q6, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, CAGCTG_AP4_Q5, GOBP_PROTEIN_MATURATION, GOBP_PROTEIN_FOLDING, RICKMAN_HEAD_AND_NECK_CANCER_A, GOBP_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, MARSON_BOUND_BY_FOXP3_STIMULATED, chr12p12, GOMF_INTRAMOLECULAR_OXIDOREDUCTASE_ACTIVITY, GOMF_ISOMERASE_ACTIVITY, FEVR_CTNNB1_TARGETS_UP, GOMF_PROTEIN_DISULFIDE_ISOMERASE_ACTIVITY

GO Biological Process (3): protein folding (GO:0006457), response to unfolded protein (GO:0006986), response to endoplasmic reticulum stress (GO:0034976)

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

GO Cellular Component (2): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
cellular response to stress	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1251 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERP27	PDIA3	P30101	945
ERP27	CALR	P27797	703
ERP27	TXN	P10599	689
ERP27	ERP29	P30040	605
ERP27	ERP44	Q9BS26	569
ERP27	TMX3	Q96JJ7	568
ERP27	PDIA5	Q14554	558
ERP27	TXNDC12	O95881	516
ERP27	TXNDC5	Q8NBS9	513
ERP27	AGR3	Q8TD06	496
ERP27	CLSTN3	Q9BQT9	491
ERP27	TMX1	Q9H3N1	486
ERP27	TMX4	Q9H1E5	476
ERP27	CANX	P27824	468
ERP27	DNAJC10	Q8IXB1	464
ERP27	AGR2	O95994	464

IntAct

48 interactions, top by confidence:

A	B	Type	Score
TAP1	TAPBP	psi-mi:“MI:0914”(association)	0.800
ERP27	SGTA	psi-mi:“MI:0915”(physical association)	0.780
SGTA	ERP27	psi-mi:“MI:0915”(physical association)	0.780
EEF1D	ERP27	psi-mi:“MI:0915”(physical association)	0.740
ERP27	UBQLN1	psi-mi:“MI:0915”(physical association)	0.670
UBQLN1	ERP27	psi-mi:“MI:0915”(physical association)	0.670
ERP27	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	ERP27	psi-mi:“MI:0915”(physical association)	0.560
C12orf60	ERP27	psi-mi:“MI:0915”(physical association)	0.560
GOLGA8F	ERP27	psi-mi:“MI:0915”(physical association)	0.560
ERP27	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
UBL4A	ERP27	psi-mi:“MI:0915”(physical association)	0.560
ERP27	MED20	psi-mi:“MI:0915”(physical association)	0.560
BLOC1S2	ERP27	psi-mi:“MI:0915”(physical association)	0.560
HTT	ERP27	psi-mi:“MI:0915”(physical association)	0.560
DDX11	DNAJA2	psi-mi:“MI:0914”(association)	0.530

BioGRID (30): ERP27 (Two-hybrid), ERP27 (Two-hybrid), ERP27 (Two-hybrid), ERP27 (Two-hybrid), ERP27 (Two-hybrid), ERP27 (Two-hybrid), GOLGA8F (Two-hybrid), C12orf60 (Two-hybrid), UBQLN2 (Two-hybrid), BLOC1S2 (Two-hybrid), VARS (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), CARS (Affinity Capture-MS), EEF1D (Affinity Capture-MS), EEF1B2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M1N5Y4, A3KPF5, D7SFH9, O13811, O44342, P12865, P32474, P38658, P52588, Q0E0I1, Q0JD42, Q10057, Q17688, Q32L47, Q43116, Q498R3, Q4N4N8, Q53LQ0, Q54EN4, Q5FVM7, Q5R5L3, Q5RCM7, Q5WA72, Q5XI02, Q5ZKZ4, Q66GQ3, Q67IX6, Q69ST6, Q6AUC6, Q6NRT6, Q6P5E4, Q7XRB5, Q8IXB1, Q8N807, Q8VX13, Q8VZQ0, Q8W4J3, Q94F09, Q95LM0, Q96DN0

Diamond homologs: D3Z6P0, D4B2L8, G4NFB7, O13811, O22263, O48773, P00275, P04785, P05307, P07237, P08003, P09102, P09103, P0AA25, P0AA26, P0AA27, P0AA28, P0AA29, P0AA30, P11598, P13667, P17967, P21195, P27773, P29828, P30101, P34329, P38657, P38658, P38659, P38660, P38661, P52588, P52589, P54399, P55059, P75512, P80284, P97493, P97615

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1375 predictions. Top by Δscore:

Variant	Effect	Δscore
12:14915672:C:CT	acceptor_gain	1.0000
12:14917322:T:C	acceptor_gain	1.0000
12:14917325:CAG:C	acceptor_gain	1.0000
12:14917326:A:T	acceptor_gain	1.0000
12:14917327:G:GC	acceptor_gain	1.0000
12:14917332:G:C	acceptor_gain	1.0000
12:14917332:G:GC	acceptor_gain	1.0000
12:14921045:CTAC:C	acceptor_gain	1.0000
12:14933145:A:AC	donor_gain	1.0000
12:14933146:C:CC	donor_gain	1.0000
12:14934852:TTAC:T	donor_loss	1.0000
12:14934853:TACCA:T	donor_loss	1.0000
12:14934854:A:AC	donor_gain	1.0000
12:14934855:C:CT	donor_gain	1.0000
12:14934855:CCAGG:C	donor_gain	1.0000
12:14934989:AAATC:A	acceptor_gain	1.0000
12:14934992:TC:T	acceptor_gain	1.0000
12:14934993:CC:C	acceptor_gain	1.0000
12:14934994:C:CC	acceptor_gain	1.0000
12:14934994:C:T	acceptor_gain	1.0000
12:14937948:TAAC:T	donor_loss	1.0000
12:14937949:AACCT:A	donor_loss	1.0000
12:14938049:CCAT:C	acceptor_gain	1.0000
12:14938050:CAT:C	acceptor_gain	1.0000
12:14938050:CATC:C	acceptor_gain	1.0000
12:14938051:AT:A	acceptor_gain	1.0000
12:14938052:TCTAG:T	acceptor_loss	1.0000
12:14938053:C:CC	acceptor_gain	1.0000
12:14938053:CT:C	acceptor_loss	1.0000
12:14914779:CTTT:C	acceptor_gain	0.9900

AlphaMissense

1817 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:14915678:A:C	F195L	0.976
12:14915678:A:T	F195L	0.976
12:14915680:A:G	F195L	0.976
12:14934919:G:C	S90R	0.974
12:14934919:G:T	S90R	0.974
12:14934921:T:G	S90R	0.974
12:14917198:C:G	A186P	0.964
12:14934860:C:G	R110P	0.957
12:14915507:G:C	F252L	0.956
12:14915507:G:T	F252L	0.956
12:14915509:A:G	F252L	0.956
12:14917197:G:T	A186D	0.953
12:14917263:A:G	L164P	0.952
12:14917210:A:C	Y182D	0.946
12:14915596:C:G	A223P	0.944
12:14920977:G:C	F135L	0.943
12:14920977:G:T	F135L	0.943
12:14920979:A:G	F135L	0.943
12:14937962:C:T	G62D	0.938
12:14915519:A:C	F248L	0.936
12:14915519:A:T	F248L	0.936
12:14915521:A:G	F248L	0.936
12:14915590:A:C	Y225D	0.935
12:14937958:G:C	F63L	0.929
12:14937958:G:T	F63L	0.929
12:14937960:A:G	F63L	0.929
12:14937968:A:T	V60D	0.928
12:14934861:G:T	R110S	0.927
12:14915627:G:C	F212L	0.925
12:14915627:G:T	F212L	0.925

dbSNP variants (sampled 300 via entrez): RS1000374341 (12:14926023 T>C), RS1000414203 (12:14931818 G>A,C), RS1000434611 (12:14936917 G>A,T), RS1000508491 (12:14940469 A>G), RS1000686643 (12:14935644 C>T), RS1000717024 (12:14935910 T>C,G), RS1000801089 (12:14921112 T>C), RS1000807224 (12:14936718 C>A,G,T), RS1000808452 (12:14920821 T>C), RS1001062613 (12:14925991 C>A), RS1001195227 (12:14919830 T>C,G), RS1001219164 (12:14913786 T>C,G), RS1001232833 (12:14935967 C>T), RS1001248895 (12:14914016 C>G), RS1001301205 (12:14930717 T>C)

Disease associations

OMIM: gene MIM:610642 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005235_5	Hand grip strength	2.000000e-12
GCST009596_4	Osteoarthritis of the hand	2.000000e-15
GCST90007527_4	Low hand grip strength (60 years and older) (EWGSOP)	4.000000e-09
GCST90010716_1	Hand osteoarthritis severity (hand Klsum)	3.000000e-12
GCST90010717_1	Finger osteoarthritis severity (hand Klsum)	5.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006941	grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects cotreatment	6
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	5
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression	3
Cyclosporine	decreases expression	3
bisphenol A	affects expression	2
mercuric bromide	affects cotreatment, increases expression	2
perfluoro-n-nonanoic acid	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Ethinyl Estradiol	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
dicrotophos	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
terbufos	increases methylation	1
3,4-dichloroaniline	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
1-hydroxypyrene	decreases expression	1
pentanal	decreases expression	1

Clinical trials (associated diseases)

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