SPRR4

Summary

SPRR4 (small proline rich protein 4, HGNC:23173) is a protein-coding gene on chromosome 1q21.3, encoding Small proline-rich protein 4 (Q96PI1). Cross-linked envelope protein of keratinocytes.

Predicted to be involved in keratinization. Predicted to be located in cell cortex.

Source: NCBI Gene 163778 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 11 total
• MANE Select transcript: NM_173080

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23173
Approved symbol	SPRR4
Name	small proline rich protein 4
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000184148
Ensembl biotype	protein_coding
OMIM	616363
Entrez	163778

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000328051

RefSeq mRNA: 1 — MANE Select: NM_173080 NM_173080

CCDS: CCDS1031

Canonical transcript exons

ENST00000328051 — 2 exons

Exon	Start	End
ENSE00001293042	152970648	152970694
ENSE00001309409	152971871	152972574

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 90.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7442 / max 729.0675, expressed in 18 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5332	0.7442	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	90.59	gold quality
sperm	CL:0000019	87.32	gold quality
mammalian vulva	UBERON:0000997	84.27	gold quality
skin of abdomen	UBERON:0001416	83.27	gold quality
zone of skin	UBERON:0000014	82.54	gold quality
skin of leg	UBERON:0001511	81.30	gold quality
nipple	UBERON:0002030	80.32	gold quality
epithelium of nasopharynx	UBERON:0001951	77.17	gold quality
cardia of stomach	UBERON:0001162	76.72	silver quality
mucosa of paranasal sinus	UBERON:0005030	76.67	gold quality
lateral nuclear group of thalamus	UBERON:0002736	72.35	gold quality
endothelial cell	CL:0000115	72.29	silver quality
penis	UBERON:0000989	71.95	gold quality
superior surface of tongue	UBERON:0007371	71.74	silver quality
body of tongue	UBERON:0011876	71.31	gold quality
vena cava	UBERON:0004087	71.22	gold quality
substantia nigra pars reticulata	UBERON:0001966	71.15	gold quality
trachea	UBERON:0003126	70.81	silver quality
thymus	UBERON:0002370	70.68	gold quality
pericardium	UBERON:0002407	70.58	gold quality
substantia nigra pars compacta	UBERON:0001965	70.41	gold quality
lateral globus pallidus	UBERON:0002476	70.40	gold quality
pylorus	UBERON:0001166	70.31	gold quality
renal medulla	UBERON:0000362	69.84	gold quality
synovial joint	UBERON:0002217	69.84	gold quality
layer of synovial tissue	UBERON:0007616	69.78	silver quality
pons	UBERON:0000988	69.61	gold quality
right testis	UBERON:0004534	69.56	gold quality
superior vestibular nucleus	UBERON:0007227	69.29	gold quality
nasal cavity epithelium	UBERON:0005384	69.13	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting SPRR4, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-3691-5P	98.62	65.88	552

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

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sprr4	ENSMUSG00000045566
rattus_norvegicus	Sprr4	ENSRNOG00000042266

Paralogs (20): LCE2B (ENSG00000159455), SPRR2G (ENSG00000159516), LCE3D (ENSG00000163202), SPRR3 (ENSG00000163209), SPRR1B (ENSG00000169469), SPRR1A (ENSG00000169474), LCE1D (ENSG00000172155), 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 4 — Q96PI1 (reviewed: Q96PI1)

All UniProt accessions (1): Q96PI1

UniProt curated annotations — full annotation on UniProt →

Function. Cross-linked envelope protein of keratinocytes. Involved in UV-induced cornification.

Subcellular location. Cytoplasm. Cell cortex.

Post-translational modifications. Cross-linked to membrane proteins by transglutaminase.

Induction. By UV irradiation.

Similarity. Belongs to the cornifin (SPRR) family.

RefSeq proteins (1): NP_775103* (*=MANE)

Domains & families (InterPro)

UniProt features (5 total): compositionally biased region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PI1-F1	67.35	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, chr1q21, MGGAAGTG_GABP_B, MARTENS_TRETINOIN_RESPONSE_UP, PEDRIOLI_MIR31_TARGETS_UP, GOBP_KERATINOCYTE_DIFFERENTIATION, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, MIR1827, MIR765, MIR450A_1_3P

GO Biological Process (1): keratinization (GO:0031424)

GO Molecular Function (0):

GO Cellular Component (2): cell cortex (GO:0005938), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
keratinocyte differentiation	1
multicellular organismal process	1
cytoplasm	1
cell periphery	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPRR4	LCE2A	Q5TA79	685
SPRR4	SPRR3	Q9UBC9	668
SPRR4	LORICRIN	P23490	661
SPRR4	KPRP	Q5T749	646
SPRR4	IVL	P07476	627
SPRR4	TCHHL1	Q5QJ38	626
SPRR4	LELP1	Q5T871	604
SPRR4	LCE3A	Q5TA76	532
SPRR4	LCE3C	Q5T5A8	530
SPRR4	LCE1A	Q5T7P2	506
SPRR4	LCE6A	A0A183	505
SPRR4	KRTAP2-1	Q9BYU5	500
SPRR4	SPRR2A	P35326	489
SPRR4	S100A2	P29034	480
SPRR4	LCE3E	Q5T5B0	475

IntAct

2 interactions, top by confidence:

A	B	Type	Score
	EBAG9	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): SPRR4 (Affinity Capture-MS), SPRR4 (Protein-RNA), APP (Reconstituted Complex)

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: Q8CGN8, Q96PI1

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	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

136 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152970692:CTGG:C	donor_loss	0.9800
1:152970695:G:GA	donor_loss	0.9800
1:152970696:T:TC	donor_loss	0.9800
1:152971868:TAG:T	acceptor_loss	0.9800
1:152971869:A:C	acceptor_loss	0.9800
1:152971870:G:C	acceptor_loss	0.9800
1:152970695:G:GG	donor_gain	0.9700
1:152971869:A:AG	acceptor_gain	0.9700
1:152971870:G:GG	acceptor_gain	0.9700
1:152970699:G:GG	donor_gain	0.9500
1:152971870:GGCT:G	acceptor_gain	0.9500
1:152970698:A:AG	donor_gain	0.9400
1:152971868:TAGG:T	acceptor_gain	0.9400
1:152971870:GGCTC:G	acceptor_gain	0.9400
1:152970692:CTG:C	donor_gain	0.9100
1:152970697:AA:A	donor_loss	0.9100
1:152971869:AG:A	acceptor_gain	0.9100
1:152971870:GG:G	acceptor_gain	0.9100
1:152970693:TG:T	donor_gain	0.9000
1:152970694:GG:G	donor_gain	0.9000
1:152971858:C:A	acceptor_gain	0.9000
1:152970690:CTCTG:C	donor_gain	0.8900
1:152971869:AGGC:A	acceptor_gain	0.8900
1:152970803:G:T	donor_gain	0.8800
1:152971867:TTAGG:T	acceptor_gain	0.8600
1:152971870:GGC:G	acceptor_gain	0.8600
1:152970691:TCTG:T	donor_gain	0.8500
1:152971859:G:A	acceptor_gain	0.8500
1:152971844:AT:A	acceptor_gain	0.8300
1:152971281:GGTGC:G	donor_gain	0.7700

AlphaMissense

514 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152971962:G:C	K24N	0.753
1:152971962:G:T	K24N	0.753
1:152971969:T:C	C27R	0.629
1:152971971:T:G	C27W	0.614

dbSNP variants (sampled 300 via entrez): RS1000100779 (1:152969811 G>A), RS1000169827 (1:152968497 G>T), RS1001035156 (1:152968374 T>G), RS1002156968 (1:152971426 C>T), RS1002269984 (1:152970085 A>G), RS1002612161 (1:152971520 G>A), RS1002761406 (1:152970135 T>C), RS1003062278 (1:152971649 A>C), RS1003647839 (1:152967536 G>A,C), RS1004343148 (1:152972694 G>A), RS1004411744 (1:152966829 T>C), RS1004875813 (1:152968710 A>G), RS1005616780 (1:152971886 G>A,C), RS1005619248 (1:152967621 G>C), RS1005900172 (1:152972869 G>T)

Disease associations

OMIM: gene MIM:616363 | 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

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	2
sodium arsenate	decreases expression, increases abundance	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Formaldehyde	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Lactic Acid	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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