SPRR2G

Summary

SPRR2G (small proline rich protein 2G, HGNC:11267) is a protein-coding gene on chromosome 1q21.3, encoding Small proline-rich protein 2G (Q9BYE4). Cross-linked envelope protein of keratinocytes. It is a selective cancer dependency (DepMap: 54.0% of cell lines).

Predicted to be involved in keratinocyte differentiation. Predicted to act upstream of or within response to estradiol. Predicted to be located in nucleus.

Source: NCBI Gene 6706 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 11 total
• Cancer dependency (DepMap): dependent in 54.0% of screened cell lines
• MANE Select transcript: NM_001014291

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11267
Approved symbol	SPRR2G
Name	small proline rich protein 2G
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000159516
Ensembl biotype	protein_coding
OMIM	617590
Entrez	6706

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368748

RefSeq mRNA: 1 — MANE Select: NM_001014291 NM_001014291

CCDS: CCDS30868

Canonical transcript exons

ENST00000368748 — 2 exons

Exon	Start	End
ENSE00001447893	153149582	153150131
ENSE00001447894	153150852	153150890

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 99.48.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.9560 / max 1503.8455, expressed in 42 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14598	1.9560	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
penis	UBERON:0000989	99.48	gold quality
upper arm skin	UBERON:0004263	97.95	gold quality
skin of leg	UBERON:0001511	96.89	gold quality
zone of skin	UBERON:0000014	94.30	gold quality
gingiva	UBERON:0001828	93.30	gold quality
skin of abdomen	UBERON:0001416	92.00	gold quality
gingival epithelium	UBERON:0001949	91.49	gold quality
mammalian vulva	UBERON:0000997	90.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.25	gold quality
upper leg skin	UBERON:0004262	87.29	gold quality
sperm	CL:0000019	85.43	silver quality
buccal mucosa cell	CL:0002336	83.64	silver quality
tibialis anterior	UBERON:0001385	82.59	silver quality
amniotic fluid	UBERON:0000173	82.51	silver quality
body of tongue	UBERON:0011876	82.49	gold quality
left ventricle myocardium	UBERON:0006566	79.52	gold quality
cardiac muscle of right atrium	UBERON:0003379	79.51	gold quality
tongue	UBERON:0001723	78.27	gold quality
skin of hip	UBERON:0001554	72.74	gold quality
myocardium	UBERON:0002349	70.91	gold quality
endothelial cell	CL:0000115	70.46	silver quality
superior surface of tongue	UBERON:0007371	69.90	gold quality
pancreatic ductal cell	CL:0002079	68.17	silver quality
deltoid	UBERON:0001476	66.40	gold quality
quadriceps femoris	UBERON:0001377	65.03	gold quality
nipple	UBERON:0002030	64.80	gold quality
lower esophagus mucosa	UBERON:0035834	64.65	gold quality
vastus lateralis	UBERON:0001379	64.20	gold quality
esophagus squamous epithelium	UBERON:0006920	63.88	silver quality
oral cavity	UBERON:0000167	63.60	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting SPRR2G, 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-8082	99.95	67.27	1170
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-549A-5P	96.35	68.08	587
HSA-MIR-591	96.29	68.16	611
HSA-MIR-3914	94.91	65.77	643

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 54.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish families. (PMID:18643845)
• High SPRR2G expression is associated with squamous cell carcinomas of the vulva. (PMID:23404381)

Cross-species orthologs

0 orthologs

Paralogs (20): LCE2B (ENSG00000159455), LCE3D (ENSG00000163202), SPRR3 (ENSG00000163209), SPRR1B (ENSG00000169469), SPRR1A (ENSG00000169474), LCE1D (ENSG00000172155), SPRR4 (ENSG00000184148), LCE3A (ENSG00000185962), LCE3E (ENSG00000185966), LCE5A (ENSG00000186207), LCE1E (ENSG00000186226), LCE2A (ENSG00000187173), LCE2C (ENSG00000187180), LCE2D (ENSG00000187223), LCE3B (ENSG00000187238), KPLCE (ENSG00000198854), PRR9 (ENSG00000203783), LELP1 (ENSG00000203784), LCE1F (ENSG00000240386), LCE3C (ENSG00000244057)

Protein

Protein identifiers

Small proline-rich protein 2G — Q9BYE4 (reviewed: Q9BYE4)

All UniProt accessions (1): Q9BYE4

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_001014313* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029142	SPRR2	Family

Pfam: PF14820

UniProt features (7 total): repeat 3, region of interest 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYE4-F1	77.94	0.09

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: 23 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, RICKMAN_HEAD_AND_NECK_CANCER_C, chr1q21, GOCC_CORNIFIED_ENVELOPE, FEVR_CTNNB1_TARGETS_UP, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, MIR7515, MIR9500

GO Biological Process (3): epidermis development (GO:0008544), keratinocyte differentiation (GO:0030216), keratinization (GO:0031424)

GO Molecular Function (0):

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

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
epidermal cell differentiation	1
skin development	1
keratinocyte differentiation	1
multicellular organismal process	1
plasma membrane	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPRR2G	SPRR2F	Q96RM1	784
SPRR2G	SPRR2E	P22531	775
SPRR2G	SPRR2D	P22532	751
SPRR2G	SPRR1B	P22528	725
SPRR2G	LCE3D	Q9BYE3	697
SPRR2G	LCE3E	Q5T5B0	638
SPRR2G	LCE2C	Q5TA81	615
SPRR2G	LCE2B	O14633	571
SPRR2G	LCE2D	Q5TA82	545
SPRR2G	LCE2A	Q5TA79	544
SPRR2G	LCE1B	Q5T7P3	528
SPRR2G	SPRR3	Q9UBC9	523
SPRR2G	CNFN	Q9BYD5	512
SPRR2G	SPRR1A	P35321	511
SPRR2G	CDSN	Q15517	485

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SPRR2G	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
OPG065	TUBB8B	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): SPRR2G (Affinity Capture-MS), SPRR2G (Reconstituted Complex), SPRR2G (Affinity Capture-MS), SPRR2G (Affinity Capture-MS), SPRR2G (Affinity Capture-MS), SPRR2G (Affinity Capture-MS), SPRR2G (Affinity Capture-MS), SPRR2G (Affinity Capture-MS), SPRR2G (Affinity Capture-MS), SPRR2G (Affinity Capture-MS), SPRR2G (Affinity Capture-MS), SPRR2G (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

212 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153150129:AATC:A	acceptor_loss	0.9700
1:153150130:ATC:A	acceptor_loss	0.9700
1:153150131:TCTGA:T	acceptor_loss	0.9700
1:153150132:C:CC	acceptor_gain	0.9700
1:153150132:C:CG	acceptor_loss	0.9700
1:153150133:T:A	acceptor_loss	0.9700
1:153150128:GAAT:G	acceptor_gain	0.9600
1:153150846:ACT:A	donor_loss	0.9100
1:153150847:CTC:C	donor_loss	0.9100
1:153150848:TCAC:T	donor_loss	0.9100
1:153150849:CACC:C	donor_loss	0.9100
1:153150851:C:CA	donor_loss	0.9100
1:153150844:GTACT:G	donor_loss	0.9000
1:153150127:AGAAT:A	acceptor_gain	0.8900
1:153150850:A:AC	donor_gain	0.8900
1:153150851:C:CC	donor_gain	0.8900
1:153150129:AAT:A	acceptor_gain	0.8800
1:153150130:AT:A	acceptor_gain	0.8800
1:153150845:TACT:T	donor_loss	0.8600
1:153150843:TGTAC:T	donor_loss	0.8500
1:153150134:G:C	acceptor_loss	0.8400
1:153150851:CCAGA:C	donor_gain	0.8300
1:153150543:TGC:T	donor_gain	0.8200
1:153150850:AC:A	donor_gain	0.8100
1:153150851:CC:C	donor_gain	0.8100
1:153150851:CCA:C	donor_gain	0.8000
1:153150851:CCAG:C	donor_gain	0.8000
1:153150547:CCCA:C	donor_gain	0.7300
1:153150276:TC:T	donor_gain	0.7100
1:153150542:TTG:T	donor_gain	0.7000

AlphaMissense

468 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153150077:A:G	C12R	0.827
1:153150087:G:C	C8W	0.792
1:153150089:A:G	C8R	0.786
1:153150075:G:C	C12W	0.781
1:153150076:C:G	C12S	0.772
1:153150077:A:T	C12S	0.772
1:153149892:C:A	K73N	0.763
1:153149892:C:G	K73N	0.763
1:153150093:C:A	Q6H	0.723
1:153150093:C:G	Q6H	0.723
1:153150042:G:C	C23W	0.717
1:153150044:A:G	C23R	0.705
1:153150090:C:A	Q7H	0.698
1:153150090:C:G	Q7H	0.698
1:153150030:A:C	C27W	0.697
1:153150059:A:G	C18R	0.689
1:153150106:G:A	S2F	0.681
1:153150084:C:A	K9N	0.666
1:153150084:C:G	K9N	0.666
1:153150032:A:G	C27R	0.657
1:153149893:T:A	K73M	0.654
1:153150043:C:G	C23S	0.653
1:153150044:A:T	C23S	0.653
1:153150081:C:A	Q10H	0.651
1:153150081:C:G	Q10H	0.651
1:153149898:C:A	K71N	0.647
1:153149898:C:G	K71N	0.647
1:153150088:C:G	C8S	0.631
1:153150089:A:T	C8S	0.631
1:153150076:C:T	C12Y	0.626

dbSNP variants (sampled 300 via entrez): RS1000042561 (1:153186544 CT>C,CTT), RS1000062106 (1:153171316 G>C), RS1000156643 (1:153171990 A>T), RS1000171895 (1:153155099 A>G), RS1000216065 (1:153181150 T>C), RS1000276985 (1:153187483 G>C), RS1000300645 (1:153154021 T>A), RS1000365819 (1:153175420 T>C), RS1000388275 (1:153198629 T>C,G), RS1000413777 (1:153186241 A>G), RS1000449208 (1:153161490 T>C), RS1000478264 (1:153154697 A>C,T), RS1000497624 (1:153171500 G>A,T), RS1000514325 (1:153182059 G>GCAT), RS1000582427 (1:153176329 C>T)

Disease associations

OMIM: gene MIM:617590 | 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
GCST008916_87	Asthma	2.000000e-13
GCST010039_3	Adverse response to inhaled corticosteroid treatment x age interaction in asthma	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008007	age at assessment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
hydroquinone	increases expression	2
Sodium Dodecyl Sulfate	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
sodium arsenate	decreases expression, increases abundance	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
incobotulinumtoxinA	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Arsenic	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Nickel	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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