SPRR2F

Summary

SPRR2F (small proline rich protein 2F, HGNC:11266) is a protein-coding gene on chromosome 1q21.3, encoding Small proline-rich protein 2F (Q96RM1). 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 nucleus.

Source: NCBI Gene 6705 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_001014450

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11266
Approved symbol	SPRR2F
Name	small proline rich protein 2F
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000244094
Ensembl biotype	protein_coding
OMIM	617589
Entrez	6705

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000468739

RefSeq mRNA: 2 — MANE Select: NM_001014450 NM_001014450, NM_001382255

CCDS: CCDS30867

Canonical transcript exons

ENST00000468739 — 2 exons

Exon	Start	End
ENSE00001772564	153113474	153113516
ENSE00001881943	153112121	153112752

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 97.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.6280 / max 1881.5512, expressed in 80 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14589	1.3515	39
14592	0.1538	21
14590	0.1089	22
14591	0.0138	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.18	gold quality
left ovary	UBERON:0002119	93.02	gold quality
ovary	UBERON:0000992	91.44	gold quality
esophagus mucosa	UBERON:0002469	88.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.52	gold quality
right ovary	UBERON:0002118	82.42	gold quality
left testis	UBERON:0004533	77.24	gold quality
right testis	UBERON:0004534	76.85	gold quality
testis	UBERON:0000473	76.67	gold quality
esophagus	UBERON:0001043	67.22	gold quality
tonsil	UBERON:0002372	63.25	gold quality
omental fat pad	UBERON:0010414	62.15	gold quality
vagina	UBERON:0000996	60.02	gold quality
ectocervix	UBERON:0012249	58.93	gold quality
right coronary artery	UBERON:0001625	55.07	gold quality
body of pancreas	UBERON:0001150	54.39	gold quality
minor salivary gland	UBERON:0001830	53.42	gold quality
saliva-secreting gland	UBERON:0001044	51.26	gold quality
left uterine tube	UBERON:0001303	51.10	gold quality
uterine cervix	UBERON:0000002	49.43	gold quality
skin of leg	UBERON:0001511	48.52	gold quality
right uterine tube	UBERON:0001302	47.86	gold quality
body of stomach	UBERON:0001161	47.67	gold quality
zone of skin	UBERON:0000014	47.23	gold quality
skin of abdomen	UBERON:0001416	45.89	gold quality
stomach	UBERON:0000945	45.57	gold quality
pancreas	UBERON:0001264	44.73	gold quality
adipose tissue	UBERON:0001013	44.55	gold quality
fundus of stomach	UBERON:0001160	44.13	gold quality
lower esophagus	UBERON:0013473	43.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8381	yes	1327.86
E-ANND-3	yes	11.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting SPRR2F, 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-513A-5P	100.00	69.77	2465
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-12123	99.52	71.79	2990
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-4520-3P	98.75	66.55	963
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-6880-5P	98.08	65.59	1282
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-4308	97.56	67.13	1385
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 2)

• Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish families. (PMID:18643845)
• SPRR2F expression is significantly downregulated in healthy palatal mucosa of smokers (PMID:31682009)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Small proline-rich protein 2F — Q96RM1 (reviewed: Q96RM1)

All UniProt accessions (1): Q96RM1

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 (2): NP_001014450, NP_001369184 (=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-Q96RM1-F1	75.55	0.00

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: 41 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, chr1q21, GOCC_CORNIFIED_ENVELOPE, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, MIR4441, MIR6764_5P, MIR6806_3P

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

254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPRR2F	SPRR2D	P22532	832
SPRR2F	SPRR1B	P22528	785
SPRR2F	SPRR2A	P35326	785
SPRR2F	SPRR2G	Q9BYE4	784
SPRR2F	SPRR2E	P22531	736
SPRR2F	LCE3D	Q9BYE3	576
SPRR2F	SPRR1A	P35321	522
SPRR2F	SPRR3	Q9UBC9	507
SPRR2F	CNFN	Q9BYD5	448
SPRR2F	PI3	P19957	446
SPRR2F	LCE3E	Q5T5B0	434
SPRR2F	SPRR4	Q96PI1	413
SPRR2F	LCE1C	Q5T751	394
SPRR2F	LCE2C	Q5TA81	370
SPRR2F	KRT24	Q2M2I5	367

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ATG16L1		psi-mi:“MI:0914”(association)	0.350

BioGRID (3): SPRR2F (Affinity Capture-MS), SPRR2F (Affinity Capture-MS), SPRR2F (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

175 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153112872:AATTC:A	donor_gain	1.0000
1:153112872:AATT:A	donor_gain	0.9900
1:153112876:C:A	donor_gain	0.9900
1:153113470:TCAC:T	donor_loss	0.9900
1:153113471:CA:C	donor_loss	0.9900
1:153113472:A:AC	donor_gain	0.9900
1:153113473:C:A	donor_loss	0.9900
1:153113473:C:CC	donor_gain	0.9900
1:153112752:TC:T	acceptor_loss	0.9800
1:153112753:C:CA	acceptor_loss	0.9800
1:153112753:C:CC	acceptor_gain	0.9800
1:153112754:T:G	acceptor_loss	0.9800
1:153113468:ACT:A	donor_loss	0.9800
1:153113473:CCAG:C	donor_gain	0.9800
1:153113473:CCA:C	donor_gain	0.9700
1:153113472:AC:A	donor_gain	0.9500
1:153113473:CC:C	donor_gain	0.9500
1:153113473:CCAGG:C	donor_gain	0.9500
1:153113091:T:C	donor_gain	0.9400
1:153112875:T:TA	donor_gain	0.9300
1:153112905:T:TA	donor_gain	0.9100
1:153112748:AGAAT:A	acceptor_gain	0.8900
1:153112751:AT:A	acceptor_gain	0.8900
1:153113077:T:TA	donor_gain	0.8800
1:153112902:A:AC	donor_gain	0.8700
1:153112903:C:CC	donor_gain	0.8700
1:153112755:G:C	acceptor_loss	0.8600
1:153112746:TCAGA:T	acceptor_gain	0.8500
1:153112749:GAAT:G	acceptor_gain	0.8500
1:153112872:A:AC	donor_gain	0.8300

AlphaMissense

461 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153112700:A:G	C12R	0.731
1:153112518:C:A	K72N	0.716
1:153112518:C:G	K72N	0.716
1:153112712:A:G	C8R	0.677
1:153112698:G:C	C12W	0.668
1:153112707:C:A	K9N	0.666
1:153112707:C:G	K9N	0.666
1:153112710:G:C	C8W	0.651
1:153112519:T:A	K72M	0.631
1:153112699:C:G	C12S	0.626
1:153112700:A:T	C12S	0.626
1:153112682:A:G	C18R	0.603
1:153112653:A:C	C27W	0.577
1:153112716:C:A	Q6H	0.565
1:153112716:C:G	Q6H	0.565

dbSNP variants (sampled 300 via entrez): RS1000356623 (1:153118736 T>C), RS1000765575 (1:153113794 C>A), RS1000967779 (1:153114025 T>C), RS1001133078 (1:153120276 T>A), RS1001239868 (1:153119288 A>G), RS1001290537 (1:153119455 G>A), RS1001481204 (1:153119795 A>G), RS1001740500 (1:153112950 T>C), RS1002042984 (1:153114837 C>A), RS1002085525 (1:153118348 A>G,T), RS1003107147 (1:153115753 T>C), RS1003696607 (1:153115989 A>G), RS1004301369 (1:153115173 C>T), RS1004583619 (1:153116369 T>C,G), RS1004639319 (1:153116750 G>A)

Disease associations

OMIM: gene MIM:617589 | 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 arsenite	increases expression	2
sodium arsenate	decreases expression, increases abundance	1
Zoledronic Acid	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Mustard Gas	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	increases expression	1
Valproic Acid	decreases methylation	1
beta-Naphthoflavone	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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