SPRR2B

Summary

SPRR2B (small proline rich protein 2B, HGNC:11262) is a protein-coding gene on chromosome 1q21.3, encoding Small proline-rich protein 2B (P35325). Cross-linked envelope protein of keratinocytes.

Predicted to be involved in keratinocyte differentiation. Predicted to act upstream of or within response to estradiol. Predicted to be located in cornified envelope and cytosol.

Source: NCBI Gene 6701 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_001388198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11262
Approved symbol	SPRR2B
Name	small proline rich protein 2B
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196805
Ensembl biotype	protein_coding
OMIM	182268
Entrez	6701

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368755

RefSeq mRNA: 2 — MANE Select: NM_001388198 NM_001017418, NM_001388198

CCDS: CCDS30865

Canonical transcript exons

ENST00000368755 — 2 exons

Exon	Start	End
ENSE00001447903	153070226	153070858
ENSE00003926904	153071569	153071611

Expression profiles

Bgee: expression breadth broad, 77 present calls, max score 95.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3164 / max 426.3144, expressed in 16 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14586	0.3164	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.47	gold quality
lower esophagus mucosa	UBERON:0035834	95.46	gold quality
esophagus mucosa	UBERON:0002469	85.28	gold quality
skin of leg	UBERON:0001511	75.13	gold quality
zone of skin	UBERON:0000014	71.64	gold quality
skin of abdomen	UBERON:0001416	66.90	gold quality
right testis	UBERON:0004534	62.31	gold quality
testis	UBERON:0000473	62.23	gold quality
left testis	UBERON:0004533	62.18	gold quality
left ovary	UBERON:0002119	61.11	gold quality
esophagus	UBERON:0001043	60.07	gold quality
ovary	UBERON:0000992	59.46	gold quality
right ovary	UBERON:0002118	53.70	gold quality
vagina	UBERON:0000996	53.56	gold quality
tonsil	UBERON:0002372	50.54	gold quality
adrenal tissue	UBERON:0018303	49.51	gold quality
minor salivary gland	UBERON:0001830	48.79	gold quality
saliva-secreting gland	UBERON:0001044	47.04	gold quality
ectocervix	UBERON:0012249	41.49	gold quality
right lung	UBERON:0002167	40.86	gold quality
omental fat pad	UBERON:0010414	40.09	gold quality
gall bladder	UBERON:0002110	38.39	gold quality
ganglionic eminence	UBERON:0004023	37.84	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
sural nerve	UBERON:0015488	36.16	gold quality
uterine cervix	UBERON:0000002	35.76	gold quality
multicellular organism	UBERON:0000468	34.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting SPRR2B, 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-4441	99.49	66.56	3216
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-7106-3P	97.33	65.33	644
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-12128	96.67	66.98	1471

Literature-anchored findings (GeneRIF, showing 5)

• SPR2B transcripts and protein were moderately increased in the human papillomaviurs 11- and 59-infected tissues. (PMID:14748073)
• Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish families. (PMID:18643845)
• We showed that just four genes, G3BP2, SCARB2, CSNK1A1 and SPRR2B, can classify patients as presence of lymph node metastasis negative or positive, with 80.0% accuracy. (PMID:21985131)
• An SNP in SPRR2B was predictive of asthma among white children with eczema from 2 independent populations. (PMID:22374195)
• Knockdown of the Sprr2b gene or inhibition of SPRR2B phosphorylation attenuates USP7/MDM2 binding and p53 degradation, leading to fibroblasts cell cycle arrest. (PMID:29581288)

Cross-species orthologs

0 orthologs

Paralogs (2): SPRR2D (ENSG00000163216), SPRR2E (ENSG00000203785)

Protein

Protein identifiers

Small proline-rich protein 2B — P35325 (reviewed: P35325)

All UniProt accessions (1): P35325

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.

Tissue specificity. Suprabasal layers of squamous-differentiated tissues such as epidermis, esophagus, tongue and trachea.

Induction. By UV irradiation and carcinogenic agents. During squamous differentiation of epidermal keratinocytes.

Similarity. Belongs to the cornifin (SPRR) family.

RefSeq proteins (2): NP_001017418, NP_001375127* (*=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 variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35325-F1	78.45	0.18

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: 49 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, OCT1_B, GOBP_SKIN_DEVELOPMENT, chr1q21, GOCC_CORNIFIED_ENVELOPE, OCT_Q6, ATF2_UP.V1_DN, WNT_UP.V1_DN, CTIP_DN.V1_DN, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, NOTCH_DN.V1_DN

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

0 interactions, top by confidence (×1000):

IntAct

5 interactions, top by confidence:

A	B	Type	Score
Cdk1		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
OPG065	TUBB8B	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): SPRR2B (Affinity Capture-Western), SPRR2B (Affinity Capture-MS), SPRR2B (Affinity Capture-MS), SPRR2B (Affinity Capture-MS), SPRR2B (Protein-peptide), SPRR2B (Affinity Capture-MS), SPRR2B (Affinity Capture-MS), SPRR2B (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

273 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153070588:AT:A	donor_gain	0.8700
1:153070588:ATCCT:A	donor_gain	0.7900
1:153070589:T:C	donor_gain	0.7900
1:153070816:G:A	donor_gain	0.7900
1:153070588:ATC:A	donor_gain	0.7800
1:153070447:T:C	acceptor_gain	0.7300
1:153070596:ATGCT:A	donor_gain	0.7300
1:153070749:T:TA	donor_gain	0.7300
1:153070582:AT:A	donor_gain	0.7200
1:153070589:T:TA	donor_gain	0.7100
1:153070296:CCAGG:C	acceptor_gain	0.7000
1:153070628:CT:C	donor_gain	0.7000
1:153070641:A:AC	donor_gain	0.7000
1:153070642:C:CC	donor_gain	0.7000
1:153070624:CTTG:C	donor_gain	0.6900
1:153070533:G:C	donor_gain	0.6700
1:153070579:ATTAT:A	donor_gain	0.6700
1:153070588:A:AC	donor_gain	0.6600
1:153070627:G:GC	donor_gain	0.6500
1:153070489:A:AC	donor_gain	0.6400
1:153070583:T:C	donor_gain	0.6400
1:153070594:T:A	donor_gain	0.6400
1:153070601:C:CA	donor_gain	0.6200
1:153070583:T:TA	donor_gain	0.6100
1:153070667:G:GC	donor_gain	0.6100
1:153070297:C:T	acceptor_gain	0.6000
1:153070815:TGC:T	donor_gain	0.6000
1:153070558:G:C	donor_gain	0.5900
1:153070817:CA:C	donor_gain	0.5900
1:153070297:CAGG:C	acceptor_gain	0.5800

AlphaMissense

461 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153070806:A:G	C12R	0.806
1:153070804:G:C	C12W	0.748
1:153070818:A:G	C8R	0.719
1:153070816:G:C	C8W	0.707
1:153070805:C:G	C12S	0.706
1:153070806:A:T	C12S	0.706
1:153070813:C:A	K9N	0.703
1:153070813:C:G	K9N	0.703
1:153070624:C:A	K72N	0.673
1:153070624:C:G	K72N	0.673
1:153070759:A:C	C27W	0.627
1:153070819:C:A	Q7H	0.624
1:153070819:C:G	Q7H	0.624
1:153070822:C:A	Q6H	0.619
1:153070822:C:G	Q6H	0.619
1:153070734:A:G	C36R	0.604
1:153070788:A:G	C18R	0.599
1:153070805:C:T	C12Y	0.596
1:153070625:T:A	K72M	0.587
1:153070771:G:C	C23W	0.582
1:153070761:A:G	C27R	0.581

dbSNP variants (sampled 300 via entrez): RS1000096996 (1:153084933 T>A), RS1000162148 (1:153073444 C>G,T), RS1000379882 (1:153073091 C>G,T), RS1000391997 (1:153078636 A>G), RS1000697713 (1:153074535 G>C), RS1000844930 (1:153088394 C>A), RS1001024724 (1:153083528 G>A), RS1001249213 (1:153080193 G>A), RS1001291152 (1:153085439 A>C,G), RS1001294313 (1:153088795 C>G), RS1001425229 (1:153085634 C>G), RS1001642641 (1:153081344 A>G), RS1001700294 (1:153080544 G>T), RS1001736850 (1:153073909 T>G), RS1001881293 (1:153069829 G>A,C)

Disease associations

OMIM: gene MIM:182268 | 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

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
hydroquinone	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
bisphenol A	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	increases expression	1
Air Pollutants	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Carmustine	decreases expression	1
Coal Tar	increases expression	1
Nickel	increases expression	1
Progesterone	decreases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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