SP5

Summary

SP5 (Sp5 transcription factor, HGNC:14529) is a protein-coding gene on chromosome 2q31.1, encoding Transcription factor Sp5 (Q6BEB4). Binds to GC boxes promoters elements.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within bone morphogenesis and post-anal tail morphogenesis. Predicted to be located in chromatin.

Source: NCBI Gene 389058 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• MANE Select transcript: NM_001003845

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14529
Approved symbol	SP5
Name	Sp5 transcription factor
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204335
Ensembl biotype	protein_coding
OMIM	609391
Entrez	389058

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000375281, ENST00000487037

RefSeq mRNA: 1 — MANE Select: NM_001003845 NM_001003845

CCDS: CCDS33322

Canonical transcript exons

ENST00000375281 — 2 exons

Exon	Start	End
ENSE00001466560	170716259	170718078
ENSE00001466561	170715337	170715563

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 79.37.

FANTOM5 (CAGE): breadth broad, TPM avg 5.8501 / max 333.4766, expressed in 400 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23605	2.0911	252
23614	0.8808	181
23609	0.5585	196
23607	0.4973	190
23611	0.4876	140
23603	0.2793	77
23612	0.2788	118
23610	0.2298	129
23613	0.2253	117
23606	0.1411	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endocervix	UBERON:0000458	79.37	gold quality
ectocervix	UBERON:0012249	79.04	gold quality
uterine cervix	UBERON:0000002	72.56	gold quality
skin of leg	UBERON:0001511	72.46	gold quality
germinal epithelium of ovary	UBERON:0001304	72.01	silver quality
upper leg skin	UBERON:0004262	69.40	silver quality
body of uterus	UBERON:0009853	68.84	gold quality
mammalian vulva	UBERON:0000997	68.77	gold quality
zone of skin	UBERON:0000014	68.51	gold quality
skin of hip	UBERON:0001554	67.52	silver quality
body of stomach	UBERON:0001161	66.88	gold quality
minor salivary gland	UBERON:0001830	64.65	gold quality
right lobe of liver	UBERON:0001114	64.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.51	gold quality
subcutaneous adipose tissue	UBERON:0002190	64.49	gold quality
stomach	UBERON:0000945	64.42	gold quality
skin of abdomen	UBERON:0001416	64.39	gold quality
right adrenal gland cortex	UBERON:0035827	64.17	gold quality
muscle layer of sigmoid colon	UBERON:0035805	64.00	gold quality
right adrenal gland	UBERON:0001233	63.96	gold quality
uterus	UBERON:0000995	63.91	gold quality
right coronary artery	UBERON:0001625	63.76	gold quality
mouth mucosa	UBERON:0003729	63.73	gold quality
right uterine tube	UBERON:0001302	63.69	gold quality
fundus of stomach	UBERON:0001160	63.02	gold quality
left adrenal gland	UBERON:0001234	62.43	gold quality
mucosa of stomach	UBERON:0001199	62.25	gold quality
endometrium	UBERON:0001295	62.00	gold quality
vagina	UBERON:0000996	61.87	gold quality
popliteal artery	UBERON:0002250	61.58	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	65.23
E-MTAB-8060	no	61.33
E-ANND-3	no	1.17

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CDKN1A	Repression
WNT2

JASPAR motifs

Motif	Name	Family
MA1965.1	SP5	Three-zinc finger Kruppel-related
MA1965.2	SP5	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:29044119

Upstream regulators (CollecTRI, top): CTNNB1, POU5F1, SHH, SP1, TCF7L2

miRNA regulators (miRDB)

43 targeting SP5, 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-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-495-3P	99.96	72.81	4197
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-214-3P	98.71	68.12	2128

Literature-anchored findings (GeneRIF, showing 4)

• human Sp5 is a member of Sp transcription factor family with a role in human cancers (PMID:16380080)
• SP5 negatively regulates WNT3a transcriptional programs in human pluripotent stem cells. (PMID:29044119)
• Circular RNA circSP5 promotes liver metastasis of colorectal cancer via SP5-mediated BAMBI transcription. (PMID:37596430)
• CPT1A mediates the succinylation of SP5 which activates transcription of PDPK1 to promote the viability and glycolysis of prostate cancer cells. (PMID:38494680)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sp5a	ENSDARG00000076571
mus_musculus	Sp5	ENSMUSG00000075304
rattus_norvegicus	Sp5	ENSRNOG00000054086
drosophila_melanogaster	CG3065	FBGN0034946
drosophila_melanogaster	luna	FBGN0040765
caenorhabditis_elegans		WBGENE00011926

Paralogs (22): KLF6 (ENSG00000067082), KLF8 (ENSG00000102349), KLF5 (ENSG00000102554), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), KLF7 (ENSG00000118263), KLF12 (ENSG00000118922), KLF9 (ENSG00000119138), KLF2 (ENSG00000127528), KLF16 (ENSG00000129911), KLF4 (ENSG00000136826), KLF10 (ENSG00000155090), KLF15 (ENSG00000163884), SP8 (ENSG00000164651), KLF13 (ENSG00000169926), SP7 (ENSG00000170374), KLF17 (ENSG00000171872), KLF11 (ENSG00000172059), SP6 (ENSG00000189120), SP9 (ENSG00000217236), KLF14 (ENSG00000266265), KLF18 (ENSG00000283039)

Protein

Protein identifiers

Transcription factor Sp5 — Q6BEB4 (reviewed: Q6BEB4)

All UniProt accessions (1): Q6BEB4

UniProt curated annotations — full annotation on UniProt →

Function. Binds to GC boxes promoters elements. Probable transcriptional activator that has a role in the coordination of changes in transcription required to generate pattern in the developing embryo.

Subcellular location. Nucleus.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Similarity. Belongs to the Sp1 C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_001003845* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (8 total): zinc finger region 3, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6BEB4-F1	56.01	0.02

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 74 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GTACAGG_MIR486, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_BONE_DEVELOPMENT, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, SANSOM_APC_TARGETS_UP, GOBP_BONE_MORPHOGENESIS, CTTTGTA_MIR524, GOBP_POST_ANAL_TAIL_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_MORPHOGENESIS, NUYTTEN_EZH2_TARGETS_DN, SANSOM_APC_TARGETS, SANSOM_WNT_PATHWAY_REQUIRE_MYC

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), post-anal tail morphogenesis (GO:0036342), bone morphogenesis (GO:0060349), negative regulation of transcription by RNA polymerase II (GO:0000122)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
regulation of DNA-templated transcription	1
anatomical structure morphogenesis	1
animal organ morphogenesis	1
skeletal system morphogenesis	1
bone development	1
negative regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transition metal ion binding	1
transcription cis-regulatory region binding	1
nucleic acid binding	1
DNA binding	1
cation binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SP5	CHAC2	Q8WUX2	586
SP5	ASB3	Q9Y575	546
SP5	MYO3B	Q8WXR4	506
SP5	PEX11B	O96011	499
SP5	ERF	P50548	366
SP5	ZFAND6	Q6FIF0	357
SP5	ZNF326	Q5BKZ1	355
SP5	MEI4	A8MW99	316
SP5	SLC25A36	Q96CQ1	308
SP5	CLEC18A	A5D8T8	305
SP5	ABHD12B	Q7Z5M8	301
SP5	DEPDC7	Q96QD5	296
SP5	EVX1	P49640	288
SP5	ARL8A	Q96BM9	285
SP5	ATP13A4	Q4VNC1	282

IntAct

2 interactions, top by confidence:

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

BioGRID (5): SP5 (Negative Genetic), SP5 (Affinity Capture-MS), SP5 (Affinity Capture-MS), SP5 (Affinity Capture-MS), SP5 (Two-hybrid)

ESM2 similar proteins: A0A8I6AGW3, A2A9A2, A6NMB9, A8MYZ6, E9PZZ1, J3QK54, O02755, O02756, O35392, O35767, O60548, O70220, P05554, P17676, P21272, P28033, P35713, P42582, P49715, P49716, P52952, P53566, P58012, Q12952, Q13461, Q14526, Q60843, Q61345, Q63244, Q63250, Q6BEB4, Q6VFT5, Q6VFT6, Q6ZQN5, Q70KY4, Q8IU81, Q8MIP2, Q8NDY6, Q8R2I0, Q98937

Diamond homologs: A5ABV9, O08876, O14901, O70494, O89090, O89091, P08047, P0CG40, P41696, Q01714, Q02446, Q02447, Q0VA40, Q13351, Q22678, Q3SY56, Q5XGT8, Q62445, Q64HY3, Q64HY5, Q6BEB4, Q6NW96, Q6P0J3, Q8BMJ8, Q8IXZ3, Q8K1S5, Q8TDD2, Q8VI67, Q90WR8, Q9ESX2, Q9JHX2, Q9TZ64, A1C6L9, A1DH89, A2QCJ9, B0XSK6, B8NGC8, G4N3L5, K9GKQ6, O14335

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

302 predictions. Top by Δscore:

Variant	Effect	Δscore
2:170716235:C:CA	acceptor_gain	1.0000
2:170716245:C:A	acceptor_gain	1.0000
2:170716248:C:A	acceptor_gain	1.0000
2:170715559:TCCAG:T	donor_loss	0.9900
2:170715560:CCAG:C	donor_loss	0.9900
2:170715561:CAGGT:C	donor_loss	0.9900
2:170715562:AGGTC:A	donor_loss	0.9900
2:170715563:GGTC:G	donor_loss	0.9900
2:170715564:G:T	donor_loss	0.9900
2:170715565:T:G	donor_loss	0.9900
2:170716254:T:G	acceptor_gain	0.9900
2:170716254:TGCA:T	acceptor_loss	0.9900
2:170716257:A:AG	acceptor_gain	0.9900
2:170716257:AG:A	acceptor_gain	0.9900
2:170716258:G:A	acceptor_loss	0.9900
2:170716258:G:GA	acceptor_gain	0.9900
2:170716258:GG:G	acceptor_gain	0.9900
2:170716258:GGAC:G	acceptor_gain	0.9900
2:170716258:GGACC:G	acceptor_gain	0.9900
2:170716254:T:TA	acceptor_gain	0.9800
2:170716258:GGA:G	acceptor_gain	0.9800
2:170716253:A:AG	acceptor_gain	0.9700
2:170715598:TGGA:T	donor_gain	0.9500
2:170716245:C:CA	acceptor_loss	0.9500
2:170716256:CAGGA:C	acceptor_gain	0.9500
2:170716257:AGGAC:A	acceptor_gain	0.9400
2:170716258:G:T	acceptor_gain	0.9400
2:170715863:G:GG	donor_gain	0.9300
2:170716254:TGCAG:T	acceptor_gain	0.9300
2:170716255:GCAGG:G	acceptor_gain	0.9300

AlphaMissense

2539 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:170717153:C:G	H316D	1.000
2:170717216:T:C	F337L	1.000
2:170717217:T:C	F337S	1.000
2:170717218:C:A	F337L	1.000
2:170717218:C:G	F337L	1.000
2:170717243:C:G	H346D	1.000
2:170717245:C:A	H346Q	1.000
2:170717245:C:G	H346Q	1.000
2:170717279:T:C	C358R	1.000
2:170717300:T:C	F365L	1.000
2:170717301:T:C	F365S	1.000
2:170717302:C:A	F365L	1.000
2:170717302:C:G	F365L	1.000
2:170717099:T:A	C298S	0.999
2:170717099:T:C	C298R	0.999
2:170717100:G:C	C298S	0.999
2:170717101:C:G	C298W	0.999
2:170717114:T:A	C303S	0.999
2:170717114:T:C	C303R	0.999
2:170717115:G:A	C303Y	0.999
2:170717115:G:C	C303S	0.999
2:170717116:C:G	C303W	0.999
2:170717126:T:G	Y307D	0.999
2:170717145:T:C	L313P	0.999
2:170717153:C:A	H316N	0.999
2:170717154:A:G	H316R	0.999
2:170717155:C:A	H316Q	0.999
2:170717155:C:G	H316Q	0.999
2:170717157:T:C	L317P	0.999
2:170717165:C:G	H320D	0.999

dbSNP variants (sampled 300 via entrez): RS1000468558 (2:170714323 C>A), RS1001606976 (2:170714959 G>C), RS1001912616 (2:170713738 T>A,C), RS1002156800 (2:170715198 T>G), RS1002567696 (2:170717031 G>A,T), RS1003521349 (2:170718381 G>A), RS1003920675 (2:170715998 C>T), RS1003980245 (2:170716057 C>A), RS1004651455 (2:170717762 T>C,G), RS1004932594 (2:170717554 G>C,T), RS1005084755 (2:170715082 A>T), RS1005311000 (2:170715174 T>A,C,G), RS1006323502 (2:170716252 T>C), RS1006811268 (2:170714561 C>G,T), RS1006939195 (2:170714914 G>A,C)

Disease associations

OMIM: gene MIM:609391 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002828_11	Urate levels in obese individuals	2.000000e-06
GCST002998_2	Lobe attachment	9.000000e-12
GCST002999_2	Lobe size	1.000000e-10
GCST003001_3	Ear morphology	3.000000e-08
GCST005192_76	Lobe attachment (rater-scored or self-reported)	6.000000e-100
GCST005193_11	Lobe attachment (rater scored)	7.000000e-16
GCST005193_17	Lobe attachment (rater scored)	1.000000e-28
GCST009391_1158	Metabolite levels	6.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0007667	lobe attachment
EFO:0007666	lobe size
EFO:0007664	outer ear morphology trait
EFO:0010460	anthranilic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	5
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
Tetrachlorodibenzodioxin	decreases expression	3
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	decreases expression	1
mercuric bromide	affects cotreatment, decreases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	decreases expression	1
ormosil	affects binding, increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Aldehydes	increases expression	1

Clinical trials (associated diseases)

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