SPRR2D

Summary

SPRR2D (small proline rich protein 2D, HGNC:11264) is a protein-coding gene on chromosome 1q21.3, encoding Small proline-rich protein 2D (P22532). Cross-linked envelope protein of keratinocytes.

Predicted to be involved in female gonad development. Predicted to act upstream of or within response to estradiol. Located in cytoplasm.

Source: NCBI Gene 6703 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_006945

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11264
Approved symbol	SPRR2D
Name	small proline rich protein 2D
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163216
Ensembl biotype	protein_coding
OMIM	617587
Entrez	6703

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000360379, ENST00000368756, ENST00000368757, ENST00000368758

RefSeq mRNA: 2 — MANE Select: NM_006945 NM_001382248, NM_006945

CCDS: CCDS30864

Canonical transcript exons

ENST00000360379 — 2 exons

Exon	Start	End
ENSE00001407560	153039732	153040365
ENSE00001625250	153041078	153041120

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 99.26.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.6657 / max 2063.8919, expressed in 145 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14583	6.6657	145

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.26	gold quality
esophagus mucosa	UBERON:0002469	98.28	gold quality
endometrium epithelium	UBERON:0004811	93.87	silver quality
vastus lateralis	UBERON:0001379	93.68	silver quality
skin of leg	UBERON:0001511	93.65	gold quality
skin of abdomen	UBERON:0001416	93.64	gold quality
zone of skin	UBERON:0000014	93.60	gold quality
metanephric glomerulus	UBERON:0004736	93.31	silver quality
epithelium of bronchus	UBERON:0002031	93.14	gold quality
quadriceps femoris	UBERON:0001377	92.74	silver quality
cerebellar vermis	UBERON:0004720	91.97	silver quality
trachea	UBERON:0003126	91.26	silver quality
thymus	UBERON:0002370	90.43	gold quality
layer of synovial tissue	UBERON:0007616	89.99	silver quality
dorsal plus ventral thalamus	UBERON:0001897	89.64	silver quality
paraflocculus	UBERON:0005351	87.55	gold quality
dorsal root ganglion	UBERON:0000044	87.52	silver quality
frontal pole	UBERON:0002795	84.78	silver quality
Brodmann (1909) area 10	UBERON:0013541	83.26	silver quality
middle frontal gyrus	UBERON:0002702	83.16	silver quality
vagina	UBERON:0000996	82.38	gold quality
esophagus	UBERON:0001043	81.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.01	silver quality
tonsil	UBERON:0002372	73.11	gold quality
minor salivary gland	UBERON:0001830	71.67	gold quality
ectocervix	UBERON:0012249	71.58	gold quality
saliva-secreting gland	UBERON:0001044	67.95	gold quality
uterine cervix	UBERON:0000002	66.17	gold quality
lower esophagus	UBERON:0013473	61.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.51	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	8752.40
E-ANND-3	yes	28.10
E-MTAB-10596	no	1063.63

Regulation

Is transcription factor: no

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): SPRR2B (ENSG00000196805), SPRR2E (ENSG00000203785)

Protein

Protein identifiers

Small proline-rich protein 2D — P22532 (reviewed: P22532)

Alternative names: Small proline-rich protein II

All UniProt accessions (1): P22532

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_001369177, NP_008876* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029142	SPRR2	Family

Pfam: PF14820

UniProt features (14 total): repeat 3, sequence conflict 3, region of interest 3, compositionally biased region 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22532-F1	77.37	0.07

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: 37 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, HUMMERICH_BENIGN_SKIN_TUMOR_UP, HUMMERICH_MALIGNANT_SKIN_TUMOR_UP, ONDER_CDH1_TARGETS_3_DN, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, MARTINEZ_RB1_TARGETS_UP, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, MARTINEZ_RB1_AND_TP53_TARGETS_UP, chr1q21, GOCC_CORNIFIED_ENVELOPE, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION

GO Biological Process (2): epidermis development (GO:0008544), keratinization (GO:0031424)

GO Molecular Function (0):

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
keratinocyte differentiation	1
multicellular organismal process	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
SPRR2D	SPRR2E	P22531	863
SPRR2D	SPRR2F	Q96RM1	832
SPRR2D	SPRR1B	P22528	802
SPRR2D	SPRR2A	P35326	800
SPRR2D	SPRR2G	Q9BYE4	751
SPRR2D	LCE3D	Q9BYE3	747
SPRR2D	LCE3E	Q5T5B0	719
SPRR2D	LCE1B	Q5T7P3	658
SPRR2D	LCE1E	Q5T753	645
SPRR2D	SPRR3	Q9UBC9	624
SPRR2D	LCE1C	Q5T751	615
SPRR2D	SPRR1A	P35321	582
SPRR2D	LCE2C	Q5TA81	512
SPRR2D	LCE2D	Q5TA82	503
SPRR2D	LCE3A	Q5TA76	448

IntAct

13 interactions, top by confidence:

A	B	Type	Score
GID8	PGRMC2	psi-mi:“MI:0914”(association)	0.640
MAPK6	SPRR2D	psi-mi:“MI:0915”(physical association)	0.370
PKN1	SPRR2D	psi-mi:“MI:0915”(physical association)	0.370
SFMBT1	SOX1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
ITGA9	IGLL5	psi-mi:“MI:0914”(association)	0.350
SPRR2D	HAL	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
FHIP2A	MED19	psi-mi:“MI:2364”(proximity)	0.270
GID8	SPRR2D	psi-mi:“MI:0915”(physical association)	0.000
USP13	SPRR2D	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): SPRR2D (Affinity Capture-MS), SPRR2D (Affinity Capture-MS), SFMBT1 (Affinity Capture-MS), SPRR2D (Affinity Capture-MS), SPRR2D (Affinity Capture-MS), HAL (Affinity Capture-MS), C17orf70 (Affinity Capture-MS), SPRR2D (Affinity Capture-MS), SPRR2D (Affinity Capture-MS), SPRR2D (Positive Genetic), SPRR2D (Affinity Capture-MS), SPRR2D (Affinity Capture-MS), SPRR2D (Affinity Capture-MS), SPRR2D (Affinity Capture-MS), SPRR2D (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

153 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153040366:C:CC	acceptor_gain	1.0000
1:153040361:AGGAT:A	acceptor_gain	0.9900
1:153040363:GATC:G	acceptor_loss	0.9900
1:153040364:ATCT:A	acceptor_loss	0.9900
1:153040365:TCTG:T	acceptor_loss	0.9900
1:153040366:CTG:C	acceptor_loss	0.9900
1:153040367:T:A	acceptor_loss	0.9900
1:153041071:CA:C	donor_gain	0.9900
1:153041074:T:TC	donor_loss	0.9900
1:153041075:C:CC	donor_loss	0.9900
1:153041076:ACCAG:A	donor_loss	0.9900
1:153041077:C:CT	donor_loss	0.9900
1:153040362:GGAT:G	acceptor_gain	0.9800
1:153040363:GAT:G	acceptor_gain	0.9800
1:153040364:AT:A	acceptor_gain	0.9800
1:153040485:A:C	donor_gain	0.9800
1:153041076:A:AC	donor_gain	0.9800
1:153041077:C:CC	donor_gain	0.9800
1:153040484:AACTG:A	donor_gain	0.9700
1:153040703:T:C	donor_gain	0.9700
1:153040697:T:C	donor_gain	0.9600
1:153040359:TCAGG:T	acceptor_gain	0.9500
1:153041071:CACT:C	donor_gain	0.9500
1:153041072:ACTC:A	donor_loss	0.9500
1:153041077:CCAG:C	donor_gain	0.9500
1:153041077:CCA:C	donor_gain	0.9400
1:153040375:A:AC	acceptor_gain	0.9300
1:153040676:T:TA	donor_gain	0.9300
1:153040488:G:GA	donor_gain	0.9200
1:153040505:T:TA	donor_gain	0.9200

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000734722 (1:153041917 T>G), RS1001191475 (1:153041011 C>T), RS1001513669 (1:153040264 G>A), RS1002200534 (1:153039529 A>C,G), RS1003089823 (1:153042063 A>G), RS1003152980 (1:153042312 T>C), RS1004487037 (1:153042918 C>T), RS1004822305 (1:153042609 C>A), RS1006017120 (1:153039993 C>G,T), RS1006392518 (1:153039559 A>T), RS1008458069 (1:153041563 G>A), RS1009271762 (1:153041533 T>C), RS1011675104 (1:153043114 G>C), RS1013471302 (1:153039736 T>A,C), RS1013902085 (1:153040607 C>A,G)

Disease associations

OMIM: gene MIM:617587 | 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

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
beta-Naphthoflavone	increases expression	2
sodium arsenate	decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
tamibarotene	affects expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
Acetaminophen	decreases expression	1
Allergens	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cannabidiol	increases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Lasalocid	increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Mustard Gas	increases expression	1
Nicotine	increases expression	1
Sodium Chloride	increases expression, affects cotreatment, affects localization, decreases expression	1
Thiram	increases expression	1
Tretinoin	affects expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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