SPRR1A

Summary

SPRR1A (small proline rich protein 1A, HGNC:11259) is a protein-coding gene on chromosome 1q21.3, encoding Cornifin-A (P35321). Cross-linked envelope protein of keratinocytes.

A structural constituent of skin epidermis. Involved in keratinocyte differentiation and peptide cross-linking. Located in cornified envelope.

Source: NCBI Gene 6698 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_005987

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11259
Approved symbol	SPRR1A
Name	small proline rich protein 1A
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169474
Ensembl biotype	protein_coding
OMIM	182265
Entrez	6698

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000368762, ENST00000696219

RefSeq mRNA: 2 — MANE Select: NM_005987 NM_001199828, NM_005987

CCDS: CCDS1032

Canonical transcript exons

ENST00000368762 — 2 exons

Exon	Start	End
ENSE00001447915	152985212	152985814
ENSE00003966542	152984081	152984125

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 99.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 28.9838 / max 6845.6832, expressed in 143 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5333	28.7674	139
5334	0.1048	26
5336	0.0582	19
5335	0.0533	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	99.96	gold quality
lower esophagus mucosa	UBERON:0035834	99.95	gold quality
gingiva	UBERON:0001828	99.94	gold quality
gingival epithelium	UBERON:0001949	99.93	gold quality
tongue squamous epithelium	UBERON:0006919	99.93	gold quality
pharyngeal mucosa	UBERON:0000355	99.92	gold quality
body of tongue	UBERON:0011876	99.88	gold quality
penis	UBERON:0000989	99.85	gold quality
squamous epithelium	UBERON:0006914	99.84	gold quality
buccal mucosa cell	CL:0002336	99.82	gold quality
esophagus squamous epithelium	UBERON:0006920	99.75	gold quality
oral cavity	UBERON:0000167	99.73	gold quality
esophagus mucosa	UBERON:0002469	99.73	gold quality
mammalian vulva	UBERON:0000997	99.72	gold quality
cervix epithelium	UBERON:0004801	99.68	gold quality
tongue	UBERON:0001723	99.63	gold quality
amniotic fluid	UBERON:0000173	99.41	gold quality
superior surface of tongue	UBERON:0007371	99.21	gold quality
epithelium of esophagus	UBERON:0001976	99.10	gold quality
skin of abdomen	UBERON:0001416	98.65	gold quality
upper arm skin	UBERON:0004263	98.49	gold quality
nipple	UBERON:0002030	98.16	gold quality
periodontal ligament	UBERON:0008266	98.09	gold quality
skin of leg	UBERON:0001511	97.83	gold quality
upper leg skin	UBERON:0004262	97.70	gold quality
zone of skin	UBERON:0000014	97.60	gold quality
nasal cavity epithelium	UBERON:0005384	94.60	gold quality
vagina	UBERON:0000996	93.98	gold quality
hair follicle	UBERON:0002073	89.45	gold quality
uterine cervix	UBERON:0000002	88.32	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	17062.18
E-CURD-114	yes	607.40
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, ELF3, JUN, KLF4

miRNA regulators (miRDB)

11 targeting SPRR1A, 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-548AT-5P	99.96	70.83	2666
HSA-MIR-609	99.82	64.26	505
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-4268	94.45	64.09	819
HSA-MIR-6826-5P	93.80	67.42	514

Literature-anchored findings (GeneRIF, showing 9)

• Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish families. (PMID:18643845)
• the deregulated increase in SPRR1A expression in chronic atopic skin lesions reflects an insufficient rise in SPRR transcripts, unable to compensate for the lack of LOR and thus contributing to the persistence of chronic atopic dermatitis skin lesions. (PMID:19672094)
• A expression may be useful as a prognostic factor for diffuse large B-cell lymphoma. (PMID:24886019)
• the SPRR1A status might play an important role in the prognosis of postmenopausal breast carcinoma patients, especially that of progesterone receptor-positive subgroups. (PMID:25424702)
• mRNA levels of LELP1, SPRR1Av1, and SPRR1Av2 were significantly higher in the skin of patients with AD compared with the control group. (PMID:27304082)
• The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial-like head and neck carcinoma subtypes. (PMID:30652380)
• Small proline-rich protein 1A promotes lung adenocarcinoma progression and indicates unfavorable clinical outcomes. (PMID:35263193)
• Survival-related indicators ALOX12B and SPRR1A are associated with DNA damage repair and tumor microenvironment status in HPV 16-negative head and neck squamous cell carcinoma patients. (PMID:35768785)
• SPRR1A is a key downstream effector of MiR-150 during both maladaptive cardiac remodeling in mice and human cardiac fibroblast activation. (PMID:37468478)

Cross-species orthologs

0 orthologs

Paralogs (20): LCE2B (ENSG00000159455), SPRR2G (ENSG00000159516), LCE3D (ENSG00000163202), SPRR3 (ENSG00000163209), SPRR1B (ENSG00000169469), 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

Cornifin-A — P35321 (reviewed: P35321)

Alternative names: 19 kDa pancornulin, SPRK, Small proline-rich protein IA

All UniProt accessions (1): P35321

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_001186757, NP_005978* (*=MANE)

Domains & families (InterPro)

Pfam: PF02389

UniProt features (18 total): repeat 8, region of interest 4, sequence variant 2, sequence conflict 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35321-F1	69.36	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: 91 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, JAEGER_METASTASIS_DN, GOBP_PEPTIDE_CROSS_LINKING, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GGGTGGRR_PAX4_03, PAX2_01, CHANG_IMMORTALIZED_BY_HPV31_DN, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, MARTINEZ_RB1_TARGETS_UP, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, MODULE_301, HUPER_BREAST_BASAL_VS_LUMINAL_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN

GO Biological Process (5): epidermis development (GO:0008544), peptide cross-linking (GO:0018149), keratinocyte differentiation (GO:0030216), cornification (GO:0070268), 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), 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
protein modification process	1
epidermal cell differentiation	1
skin development	1
programmed cell death	1
keratinization	1
cornified envelope assembly	1
keratinocyte differentiation	1
multicellular organismal process	1
molecular_function	1
structural molecule activity	1
binding	1
plasma membrane	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPRR1A	IVL	P07476	899
SPRR1A	LORICRIN	P23490	827
SPRR1A	SPRR2A	P35326	801
SPRR1A	TCHH	Q07283	724
SPRR1A	S100A6	P06703	719
SPRR1A	FLG	P20930	715
SPRR1A	FLG2	Q5D862	703
SPRR1A	C4BPA	P04003	659
SPRR1A	S100A10	P08206	620
SPRR1A	LCE3D	Q9BYE3	595
SPRR1A	SPRR2D	P22532	582
SPRR1A	LCE1C	Q5T751	558
SPRR1A	LCE3E	Q5T5B0	548
SPRR1A	SPRR2F	Q96RM1	522
SPRR1A	SPRR2G	Q9BYE4	511

IntAct

16 interactions, top by confidence:

A	B	Type	Score
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
SPRR1A	GLIS1	psi-mi:“MI:0915”(physical association)	0.560
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
ST6GALNAC6	A2ML1	psi-mi:“MI:0914”(association)	0.350
GABPA	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
MRM1	RIMOC1	psi-mi:“MI:0914”(association)	0.350
NUDT3	A2ML1	psi-mi:“MI:0914”(association)	0.350
P/V/C	HSPA5	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350
INSR	UBXN8	psi-mi:“MI:0914”(association)	0.350
GLIS1	SPRR1A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), GLIS1 (Two-hybrid), SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), SPRR1A (Affinity Capture-MS), SPRR1A (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: P22528, P35321, P35322, P35323

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

45 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152985494:G:GT	donor_gain	0.8000
1:152985494:GAA:G	donor_gain	0.7700
1:152985497:G:GG	donor_gain	0.7500
1:152985321:G:GT	donor_gain	0.6100
1:152985412:TTCCA:T	donor_gain	0.4500
1:152985496:AGTA:A	donor_loss	0.4500
1:152985497:GT:G	donor_loss	0.4500
1:152985498:T:A	donor_loss	0.4500
1:152985363:GTGCC:G	donor_gain	0.4400
1:152985364:TGCCT:T	donor_gain	0.4400
1:152985365:GCCTG:G	donor_gain	0.4400
1:152985499:A:C	donor_loss	0.4400
1:152985367:C:G	donor_gain	0.4300
1:152985435:GTGCC:G	donor_gain	0.4100
1:152985436:TGCCT:T	donor_gain	0.4100
1:152985437:GCCTG:G	donor_gain	0.4100
1:152985292:TGA:T	donor_gain	0.3900
1:152985294:A:AG	donor_gain	0.3900
1:152985295:A:G	donor_gain	0.3800
1:152985457:C:CA	acceptor_gain	0.3800
1:152985293:G:A	donor_gain	0.3600
1:152985439:C:G	donor_gain	0.3400
1:152985495:AA:A	donor_gain	0.3300
1:152985492:CAGAA:C	donor_gain	0.3200
1:152985493:AGAA:A	donor_gain	0.3200
1:152985496:A:G	donor_gain	0.3200
1:152985455:AACGG:A	acceptor_gain	0.3100
1:152985454:CAACG:C	acceptor_gain	0.3000
1:152985322:A:T	donor_gain	0.2800
1:152985453:TCAAC:T	acceptor_gain	0.2500

AlphaMissense

575 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152985497:G:C	K89N	0.583
1:152985497:G:T	K89N	0.583

dbSNP variants (sampled 300 via entrez): RS1000493540 (1:152984535 T>C), RS1000506973 (1:152985353 C>A,T), RS1000987258 (1:152986046 T>C), RS1001524407 (1:152985140 A>C), RS1001896493 (1:152983056 G>A,T), RS1002656876 (1:152982219 G>C,T), RS1004511999 (1:152986062 T>C), RS1005000806 (1:152982821 C>T), RS1005316713 (1:152984117 G>A), RS1005346333 (1:152983459 G>A), RS1006821178 (1:152984439 G>A), RS1007181365 (1:152984748 A>C,T), RS1009734664 (1:152986109 G>A), RS1010086434 (1:152982195 C>T), RS1011325199 (1:152982487 G>A)

Disease associations

OMIM: gene MIM:182265 | 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

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	4
sodium arsenite	decreases expression, increases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
Endosulfan	increases expression	2
deoxynivalenol	decreases expression	1
sodium arsenate	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Antimony Potassium Tartrate	decreases expression	1
Arsenic	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Calcitriol	decreases expression	1
Estradiol	affects cotreatment, decreases expression, increases expression	1
Fluorouracil	increases expression	1
Hydralazine	affects cotreatment, decreases expression	1
Lasalocid	increases expression	1
Nickel	increases expression	1
Tetradecanoylphorbol Acetate	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects cotreatment, decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Permethrin	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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