SPRR2E

Summary

SPRR2E (small proline rich protein 2E, HGNC:11265) is a protein-coding gene on chromosome 1q21.3, encoding Small proline-rich protein 2E (P22531). Cross-linked envelope protein of keratinocytes.

This gene encodes a member of a family of small proline-rich proteins clustered in the epidermal differentiation complex on chromosome 1q21. The encoded protein, along with other family members, is a component of the cornified cell envelope that forms beneath the plasma membrane in terminally differentiated stratified squamous epithelia. This envelope serves as a barrier against extracellular and environmental factors. The seven SPRR2 genes (A-G) appear to have been homogenized by gene conversion compared to others in the cluster that exhibit greater differences in protein structure.

Source: NCBI Gene 6704 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_001024209

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11265
Approved symbol	SPRR2E
Name	small proline rich protein 2E
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000203785
Ensembl biotype	protein_coding
OMIM	617588
Entrez	6704

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000368750, ENST00000368751

RefSeq mRNA: 1 — MANE Select: NM_001024209 NM_001024209

CCDS: CCDS30866

Canonical transcript exons

ENST00000368750 — 2 exons

Exon	Start	End
ENSE00001447895	153093135	153093770
ENSE00001596930	153094484	153094526

Expression profiles

Bgee: expression breadth ubiquitous, 114 present calls, max score 99.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.7193 / max 1413.8380, expressed in 58 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14588	1.7193	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.36	gold quality
skin of leg	UBERON:0001511	98.34	gold quality
zone of skin	UBERON:0000014	98.04	gold quality
esophagus mucosa	UBERON:0002469	97.78	gold quality
skin of abdomen	UBERON:0001416	97.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.83	silver quality
esophagus	UBERON:0001043	81.62	gold quality
vagina	UBERON:0000996	81.11	gold quality
minor salivary gland	UBERON:0001830	72.87	gold quality
ectocervix	UBERON:0012249	72.13	gold quality
tonsil	UBERON:0002372	72.00	gold quality
saliva-secreting gland	UBERON:0001044	69.34	gold quality
right coronary artery	UBERON:0001625	67.85	gold quality
uterine cervix	UBERON:0000002	65.42	gold quality
ovary	UBERON:0000992	65.17	gold quality
left ovary	UBERON:0002119	65.14	gold quality
lower esophagus	UBERON:0013473	63.48	gold quality
lower esophagus muscularis layer	UBERON:0035833	63.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	62.08	gold quality
gastrocnemius	UBERON:0001388	62.07	gold quality
right ovary	UBERON:0002118	61.77	gold quality
heart left ventricle	UBERON:0002084	60.03	gold quality
right lobe of liver	UBERON:0001114	59.35	gold quality
body of pancreas	UBERON:0001150	59.07	gold quality
right atrium auricular region	UBERON:0006631	58.62	gold quality
body of stomach	UBERON:0001161	58.44	gold quality
fundus of stomach	UBERON:0001160	58.20	gold quality
omental fat pad	UBERON:0010414	58.05	gold quality
tibial artery	UBERON:0007610	57.67	gold quality
popliteal artery	UBERON:0002250	57.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	6905.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting SPRR2E, 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-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-12128	96.67	66.98	1471
HSA-MIR-4794	96.47	65.53	1063
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-664A-5P	95.84	64.93	949

Literature-anchored findings (GeneRIF, showing 1)

• Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish families. (PMID:18643845)

Cross-species orthologs

0 orthologs

Paralogs (2): SPRR2D (ENSG00000163216), SPRR2B (ENSG00000196805)

Protein

Protein identifiers

Small proline-rich protein 2E — P22531 (reviewed: P22531)

Alternative names: Small proline-rich protein II

All UniProt accessions (1): P22531

UniProt curated annotations — full annotation on UniProt →

Function. Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane.

Subcellular location. Cytoplasm.

Induction. During squamous differentiation of epidermal keratinocytes.

Similarity. Belongs to the cornifin (SPRR) family.

RefSeq proteins (1): NP_001019380* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029142	SPRR2	Family

Pfam: PF14820

UniProt features (10 total): repeat 3, region of interest 3, compositionally biased region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22531-F1	77.66	0.04

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6809371	Formation of the cornified envelope
R-HSA-1266738	Developmental Biology
R-HSA-6805567	Keratinization

MSigDB gene sets: 30 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, CHANG_IMMORTALIZED_BY_HPV31_DN, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, chr1q21, GOCC_CORNIFIED_ENVELOPE, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, GOBP_CORNIFICATION, GOMF_STRUCTURAL_CONSTITUENT_OF_SKIN_EPIDERMIS, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, GOBP_EPITHELIAL_CELL_DIFFERENTIATION

GO Biological Process (4): epidermis development (GO:0008544), cornification (GO:0070268), peptide cross-linking (GO:0018149), keratinization (GO:0031424)

GO Molecular Function (3): structural molecule activity (GO:0005198), structural constituent of skin epidermis (GO:0030280), protein binding (GO:0005515)

GO Cellular Component (3): cornified envelope (GO:0001533), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Keratinization	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
tissue development	1
programmed cell death	1
keratinization	1
cornified envelope assembly	1
protein modification process	1
keratinocyte differentiation	1
multicellular organismal process	1
molecular_function	1
structural molecule activity	1
binding	1
plasma membrane	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

378 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPRR2E	SPRR2D	P22532	863
SPRR2E	SPRR2G	Q9BYE4	775
SPRR2E	SPRR1B	P22528	766
SPRR2E	SPRR2F	Q96RM1	736
SPRR2E	SPRR2A	P35326	728
SPRR2E	LCE3E	Q5T5B0	620
SPRR2E	LCE3D	Q9BYE3	609
SPRR2E	SPRR3	Q9UBC9	571
SPRR2E	CNFN	Q9BYD5	542
SPRR2E	LCE1C	Q5T751	528
SPRR2E	SPRR1A	P35321	507
SPRR2E	LCE2C	Q5TA81	506
SPRR2E	LCE2A	Q5TA79	480
SPRR2E	LCE3A	Q5TA76	471
SPRR2E	SPRR4	Q96PI1	447

IntAct

23 interactions, top by confidence:

A	B	Type	Score
CBX1	ZNF292	psi-mi:“MI:0914”(association)	0.530
RYK	PCDH7	psi-mi:“MI:0914”(association)	0.530
Cdk1		psi-mi:“MI:0915”(physical association)	0.400
Akap12		psi-mi:“MI:0915”(physical association)	0.400
Retreg2		psi-mi:“MI:0915”(physical association)	0.400
Them6		psi-mi:“MI:0915”(physical association)	0.400
SPRR2E	ARID3C	psi-mi:“MI:0915”(physical association)	0.400
	AP3B1	psi-mi:“MI:0914”(association)	0.350
TP53BP1	BCKDK	psi-mi:“MI:0914”(association)	0.350
WRAP73	GGCT	psi-mi:“MI:0914”(association)	0.350
DDR2	PLD2	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
OPG065	TUBB8B	psi-mi:“MI:0914”(association)	0.350
RASSF2	SPRR2E	psi-mi:“MI:0914”(association)	0.350
RASSF9	CCDC85C	psi-mi:“MI:0914”(association)	0.350
RASSF10	CCDC85C	psi-mi:“MI:0914”(association)	0.350
E2F6	GLUD1	psi-mi:“MI:0914”(association)	0.350
SUV39H2	ARG1	psi-mi:“MI:0914”(association)	0.350
FHIP2B	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (33): SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), S100A9 (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS), SPRR2E (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTR4, A6QNZ4, O14633, O70554, O70555, O70556, O70557, O70558, O70559, O70560, O70562, P15265, P22528, P22531, P22532, P35321, P35322, P35323, P35324, P35325, P35326, P49901, Q28658, Q32L04, Q4KL71, Q4R956, Q5T5B0, Q5T750, Q5T752, Q5T754, Q5T870, Q5T871, Q5TA76, Q5TA77, Q5TA78, Q5TA79, Q5TA81, Q5TA82, Q5TCM9, Q62266

Diamond homologs: O70554, O70555, O70556, O70557, O70558, O70559, O70560, O70562, P22531, P22532, P35325, P35326, Q4KL71, Q96RM1, Q9BYE4, Q9CQK8, O70561

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

117 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153093891:G:C	donor_gain	1.0000
1:153093908:T:TA	donor_gain	1.0000
1:153093770:TC:T	acceptor_loss	0.9800
1:153093771:C:T	acceptor_loss	0.9800
1:153093772:T:G	acceptor_loss	0.9800
1:153093890:AGCT:A	donor_gain	0.9800
1:153094479:CTCA:C	donor_loss	0.9800
1:153094480:TCACC:T	donor_loss	0.9800
1:153094481:CAC:C	donor_loss	0.9800
1:153094482:A:T	donor_loss	0.9800
1:153094483:C:CT	donor_loss	0.9800
1:153093771:C:CC	acceptor_gain	0.9700
1:153094478:ACT:A	donor_loss	0.9700
1:153094482:A:AC	donor_gain	0.9700
1:153094483:C:CC	donor_gain	0.9700
1:153094477:GACT:G	donor_loss	0.9600
1:153094483:CCAG:C	donor_gain	0.9500
1:153094483:CCA:C	donor_gain	0.9400
1:153094482:AC:A	donor_gain	0.8900
1:153094483:CC:C	donor_gain	0.8900
1:153094483:CCAGG:C	donor_gain	0.8900
1:153093769:AT:A	acceptor_gain	0.8800
1:153093890:A:AC	donor_gain	0.8800
1:153093766:AGAAT:A	acceptor_gain	0.8600
1:153093773:G:C	acceptor_loss	0.8600
1:153094370:TAAG:T	donor_gain	0.8400
1:153094476:AGAC:A	donor_loss	0.8400
1:153093767:GAAT:G	acceptor_gain	0.8300
1:153093764:TCAGA:T	acceptor_gain	0.8200
1:153093895:T:A	donor_gain	0.8100

AlphaMissense

463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153093718:A:G	C12R	0.774
1:153093716:G:C	C12W	0.704
1:153093730:A:G	C8R	0.704
1:153093536:C:A	K72N	0.686
1:153093536:C:G	K72N	0.686
1:153093725:C:A	K9N	0.686
1:153093725:C:G	K9N	0.686
1:153093728:G:C	C8W	0.681
1:153093717:C:G	C12S	0.674
1:153093718:A:T	C12S	0.674
1:153093700:A:G	C18R	0.642
1:153093734:C:A	Q6H	0.631
1:153093734:C:G	Q6H	0.631
1:153093671:A:C	C27W	0.620
1:153093646:A:G	C36R	0.610
1:153093537:T:A	K72M	0.593
1:153093731:C:A	Q7H	0.591
1:153093731:C:G	Q7H	0.591
1:153093673:A:G	C27R	0.574

dbSNP variants (sampled 300 via entrez): RS1000792713 (1:153095172 A>G), RS1000928108 (1:153095587 T>A,C), RS1002482625 (1:153095861 G>C), RS1005797130 (1:153093631 A>C,G), RS1005829807 (1:153093443 A>G,T), RS1006135779 (1:153094857 A>G,T), RS1006634349 (1:153093906 C>A,T), RS1007128450 (1:153094867 G>T), RS1007417932 (1:153096239 T>C), RS1007470211 (1:153095949 A>C), RS1007810847 (1:153095122 C>T), RS1008349732 (1:153094904 A>G), RS1008556790 (1:153093401 A>C,G), RS1009101602 (1:153096171 A>G), RS1009672045 (1:153092644 T>C)

Disease associations

OMIM: gene MIM:617588 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007564_25	Asthma or allergic disease (pleiotropy)	5.000000e-09
GCST008916_87	Asthma	2.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	increases expression	1
CGP 52608	increases reaction, affects binding	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
Cadmium Chloride	decreases expression	1
beta-Naphthoflavone	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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