SOX14

Summary

SOX14 (SRY-box transcription factor 14, HGNC:11193) is a protein-coding gene on chromosome 3q22.3, encoding Transcription factor SOX-14 (O95416). Acts as a negative regulator of transcription.

This intronless gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. Mutations in this gene are suggested to be responsible for the limb defects associated with blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) and Mobius syndrome.

Source: NCBI Gene 8403 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_004189

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11193
Approved symbol	SOX14
Name	SRY-box transcription factor 14
Location	3q22.3
Locus type	gene with protein product
Status	Approved
Aliases	SOX28
Ensembl gene	ENSG00000168875
Ensembl biotype	protein_coding
OMIM	604747
Entrez	8403

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000306087

RefSeq mRNA: 1 — MANE Select: NM_004189 NM_004189

CCDS: CCDS3094

Canonical transcript exons

ENST00000306087 — 1 exons

Exon	Start	End
ENSE00001154585	137764315	137766334

Expression profiles

Bgee: expression breadth broad, 15 present calls, max score 54.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2017 / max 38.4047, expressed in 45 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38760	0.2017	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	54.24	gold quality
hypothalamus	UBERON:0001898	51.30	gold quality
lower esophagus mucosa	UBERON:0035834	46.90	silver quality
lower lobe of lung	UBERON:0008949	45.42	silver quality
substantia nigra	UBERON:0002038	45.18	gold quality
midbrain	UBERON:0001891	44.51	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
buccal mucosa cell	CL:0002336	43.07	gold quality
amniotic fluid	UBERON:0000173	42.79	gold quality
prostate gland	UBERON:0002367	42.58	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
gingiva	UBERON:0001828	42.56	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
trabecular bone tissue	UBERON:0002483	40.78	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
cortical plate	UBERON:0005343	40.35	silver quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
dorsal plus ventral thalamus	UBERON:0001897	40.22	gold quality
mammary duct	UBERON:0001765	40.19	gold quality
jejunum	UBERON:0002115	40.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.48

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
MICAL1	Unknown

JASPAR motifs

Motif	Name	Family
MA1562.1	SOX14	SOX-related factors
MA1562.2	SOX14	SOX-related factors

JASPAR matrix evidence (PMIDs): PMID:17852354

Upstream regulators (CollecTRI, top): FOXA2, FOXO4, GLI1

miRNA regulators (miRDB)

87 targeting SOX14, 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-3120-5P	100.00	65.56	965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 4)

• identified the positive control element and provided the first evidence that FOXA2 is involved in up-regulation of SOX14 expression in HepG2 and U87MG cell lines (PMID:20074681)
• these results demonstrate that SOX14 can promote proliferation and invasion capacity of cervical cancer cells by activating the Wnt/beta-catenin pathway. (PMID:25973056)
• High SOX14 expression is associated with bladder cancer. (PMID:28258492)
• SOX14 hypermethylation as a tumour biomarker in cervical cancer. (PMID:34098886)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	sox14	ENSDARG00000070929
mus_musculus	Sox14	ENSMUSG00000053747
rattus_norvegicus	Sox14	ENSRNOG00000022084
drosophila_melanogaster	Sox14	FBGN0005612
drosophila_melanogaster	Sox21a	FBGN0036411
drosophila_melanogaster	Sox102F	FBGN0039938
caenorhabditis_elegans		WBGENE00001182

Paralogs (20): SOX8 (ENSG00000005513), SOX30 (ENSG00000039600), SOX10 (ENSG00000100146), SOX6 (ENSG00000110693), SOX4 (ENSG00000124766), SOX21 (ENSG00000125285), SOX9 (ENSG00000125398), SOX15 (ENSG00000129194), SOX5 (ENSG00000134532), SOX3 (ENSG00000134595), SOX13 (ENSG00000143842), SOX17 (ENSG00000164736), SOX7 (ENSG00000171056), SOX11 (ENSG00000176887), SOX12 (ENSG00000177732), CFAP65 (ENSG00000181378), SOX2 (ENSG00000181449), SOX1 (ENSG00000182968), SRY (ENSG00000184895), SOX18 (ENSG00000203883)

Protein

Protein identifiers

Transcription factor SOX-14 — O95416 (reviewed: O95416)

Alternative names: Protein SOX-28

All UniProt accessions (1): O95416

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative regulator of transcription.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_004180* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR022097	SOX_fam	Family
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR050140	SRY-related_HMG-box_TF-like	Family

Pfam: PF00505, PF12336

UniProt features (2 total): chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95416-F1	68.13	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_CIRCADIAN_RHYTHM, RNGTGGGC_UNKNOWN, YAATNRNNNYNATT_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, GCANCTGNY_MYOD_Q6, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, EVI1_05, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, TCF4_Q5, NKX62_Q2, NF1_Q6_01, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, OCT1_03

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), nervous system development (GO:0007399), brain development (GO:0007420), visual perception (GO:0007601), entrainment of circadian clock (GO:0009649), neuron differentiation (GO:0030182), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of neuron migration (GO:2001222), regulation of DNA-templated transcription (GO:0006355)

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 activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
DNA-templated transcription	2
binding	2
negative regulation of DNA-templated transcription	1
system development	1
central nervous system development	1
animal organ development	1
head development	1
sensory perception of light stimulus	1
response to external stimulus	1
regulation of circadian rhythm	1
cell differentiation	1
generation of neurons	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
neuron migration	1
regulation of cell migration	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SOX14	C4BPA	P04003	551
SOX14	NKX2-2	O95096	463
SOX14	DBX1	A6NMT0	438
SOX14	CDR2L	Q86X02	426
SOX14	LHX9	Q9NQ69	425
SOX14	TMEM14A	Q9Y6G1	417
SOX14	LHX3	Q9UBR4	407
SOX14	TAL2	Q16559	405
SOX14	GBX2	P52951	399
SOX14	DKK4	Q9UBT3	396
SOX14	ANAPC2	Q9UJX6	395
SOX14	AKR7A2	O43488	387
SOX14	ESYT3	A0FGR9	381
SOX14	LHX5	Q9H2C1	376
SOX14	LHX1	P48742	376

IntAct

97 interactions, top by confidence:

A	B	Type	Score
SOX14	NAIF1	psi-mi:“MI:0915”(physical association)	0.670
NAIF1	SOX14	psi-mi:“MI:0915”(physical association)	0.670
CRX	SOX14	psi-mi:“MI:0915”(physical association)	0.560
SOX14	ROR2	psi-mi:“MI:0915”(physical association)	0.560
SOX14	SPMIP9	psi-mi:“MI:0915”(physical association)	0.560
FOXH1	SOX14	psi-mi:“MI:0915”(physical association)	0.560
VENTX	SOX14	psi-mi:“MI:0915”(physical association)	0.560
SOX14	KRTAP15-1	psi-mi:“MI:0915”(physical association)	0.560
APBB1	SOX14	psi-mi:“MI:0915”(physical association)	0.560
GRN	SOX14	psi-mi:“MI:0915”(physical association)	0.560
SOX14	NR3C1	psi-mi:“MI:0915”(physical association)	0.560
PSEN2	SOX14	psi-mi:“MI:0915”(physical association)	0.560
TGM2	SOX14	psi-mi:“MI:0915”(physical association)	0.560
SOX14	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
SOX14	HTT	psi-mi:“MI:0915”(physical association)	0.560
SOX14	ATXN3	psi-mi:“MI:0915”(physical association)	0.560
SOX14	ATXN1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (14): NAIF1 (Two-hybrid), SOX14 (Two-hybrid), SOX14 (Affinity Capture-MS), SOX14 (Affinity Capture-MS), SOX14 (Two-hybrid), SOX14 (Two-hybrid), SOX14 (Two-hybrid), ROR2 (Two-hybrid), TEX37 (Two-hybrid), KRTAP15-1 (Two-hybrid), SOX14 (Two-hybrid), SOX14 (Affinity Capture-MS), SOX14 (Affinity Capture-MS), SOX14 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A4IIJ8, A4QNG3, B0ZTE1, B0ZTE2, B7ZR65, O42342, O95416, P04476, P09071, P23770, P27782, P46692, P47792, P48433, P55863, P61259, P70056, Q04892, Q08478, Q1KKY3, Q1KL17, Q28447, Q28GD5, Q28IU6, Q32PP9, Q66JW3, Q68FA4, Q6DFF5, Q6EJB7, Q6NVT7, Q6RVD7, Q6VVD7, Q7SZS1, Q8AWY9, Q8AXX8, Q90481, Q90X25, Q90ZH7, Q90ZH8, Q91169

Diamond homologs: A2TED3, A4QNG3, B0ZTE1, B0ZTE2, O00570, O42569, O57401, O60248, O95416, P36389, P36390, P36393, P36395, P36396, P41225, P43267, P47792, P48046, P48430, P48431, P48432, P48433, P51501, P53783, P53784, P54231, P55863, P61259, Q04892, Q05066, Q20201, Q21305, Q24533, Q28447, Q28778, Q28783, Q28798, Q2PG84, Q2Z1R2, Q32PP9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chemokine receptors bind chemokines	6	38.7×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
chemokine-mediated signaling pathway	6	52.5×	4e-07
antimicrobial humoral immune response mediated by antimicrobial peptide	7	30.7×	4e-07
chemotaxis	6	22.0×	2e-05
cellular response to lipopolysaccharide	6	15.9×	1e-04
positive regulation of cell migration	8	13.3×	1e-05
cell-cell signaling	7	13.2×	5e-05
inflammatory response	10	10.2×	4e-06
immune response	6	7.6×	4e-03

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	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

45 predictions. Top by Δscore:

Variant	Effect	Δscore
3:137764397:A:T	donor_gain	0.9200
3:137764405:G:T	donor_gain	0.7800
3:137764424:TG:T	donor_gain	0.7700
3:137764425:GG:G	donor_gain	0.7700
3:137764418:C:T	donor_gain	0.6000
3:137765422:A:AG	acceptor_gain	0.4400
3:137765423:G:GG	acceptor_gain	0.4400
3:137765053:ACAG:A	donor_loss	0.3600
3:137765054:CAGG:C	donor_loss	0.3600
3:137765055:AGGTA:A	donor_loss	0.3600
3:137765057:G:A	donor_loss	0.3600
3:137765058:T:A	donor_loss	0.3600
3:137765538:TCTGA:T	donor_gain	0.3500
3:137765052:GACAG:G	donor_gain	0.3400
3:137765453:C:T	donor_gain	0.3400
3:137764355:A:T	donor_gain	0.3300
3:137765057:G:GG	donor_gain	0.3300
3:137764440:G:GT	donor_gain	0.3000
3:137765423:GC:G	acceptor_gain	0.3000
3:137765494:C:G	donor_gain	0.2900
3:137764396:G:GT	donor_gain	0.2800
3:137765392:ACT:A	donor_gain	0.2700
3:137765503:T:G	donor_gain	0.2700
3:137764404:GGAAC:G	donor_gain	0.2600
3:137764935:G:GC	acceptor_gain	0.2500
3:137765659:G:GA	acceptor_gain	0.2400
3:137764405:G:GT	donor_gain	0.2300
3:137765176:C:A	acceptor_gain	0.2300
3:137765485:C:A	donor_gain	0.2300
3:137764329:GC:G	donor_gain	0.2200

AlphaMissense

1553 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:137764803:C:G	H7D	1.000
3:137764807:T:A	I8N	1.000
3:137764809:A:G	K9E	1.000
3:137764810:A:T	K9M	1.000
3:137764811:G:C	K9N	1.000
3:137764811:G:T	K9N	1.000
3:137764812:C:G	R10G	1.000
3:137764812:C:T	R10W	1.000
3:137764813:G:A	R10Q	1.000
3:137764813:G:T	R10L	1.000
3:137764815:C:A	P11T	1.000
3:137764815:C:G	P11A	1.000
3:137764815:C:T	P11S	1.000
3:137764816:C:A	P11H	1.000
3:137764816:C:G	P11R	1.000
3:137764816:C:T	P11L	1.000
3:137764819:T:A	M12K	1.000
3:137764819:T:C	M12T	1.000
3:137764819:T:G	M12R	1.000
3:137764820:G:A	M12I	1.000
3:137764820:G:C	M12I	1.000
3:137764820:G:T	M12I	1.000
3:137764821:A:C	N13H	1.000
3:137764821:A:G	N13D	1.000
3:137764821:A:T	N13Y	1.000
3:137764822:A:T	N13I	1.000
3:137764823:C:A	N13K	1.000
3:137764823:C:G	N13K	1.000
3:137764824:G:A	A14T	1.000
3:137764825:C:A	A14D	1.000

dbSNP variants (sampled 300 via entrez): RS1000159882 (3:137765112 C>T), RS1000507646 (3:137763570 T>A), RS1001392390 (3:137764274 G>T), RS1001827458 (3:137762742 T>C), RS1003051101 (3:137763032 C>G,T), RS1004449220 (3:137764978 G>T), RS1004690849 (3:137763845 A>G), RS1005145250 (3:137765893 T>G), RS1005189632 (3:137763683 G>C), RS1005897070 (3:137764609 C>A,T), RS1007548183 (3:137762342 G>A), RS1008029384 (3:137766599 C>A), RS1008582887 (3:137766423 G>A), RS1008788316 (3:137766602 T>C), RS1009005250 (3:137766307 A>G)

Disease associations

OMIM: gene MIM:604747 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (1): Microphthalmia-anophthalmia-coloboma (Orphanet:98555)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002817_1	Alzheimer’s disease in APOE e4- carriers	5.000000e-07
GCST003084_7	Glucocorticoid-induced osteonecrosis	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases methylation	1
arsenite	increases methylation	1
CGP 52608	affects binding, increases reaction	1
deguelin	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A6L7	SEES3-1V human SOX14, clone1	Embryonic stem cell	Male
CVCL_A6L8	SEES3-1V human SOX14, clone2	Embryonic stem cell	Male
CVCL_A6L9	SEES3-1V human SOX14, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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