SOX11

Summary

SOX11 (SRY-box transcription factor 11, HGNC:11191) is a protein-coding gene on chromosome 2p25.2, encoding Transcription factor SOX-11 (P35716). Transcription factor that acts as a transcriptional activator. It is haploinsufficient (ClinGen: sufficient evidence).

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. The protein may function in the developing nervous system and play a role in tumorigenesis.

Source: NCBI Gene 6664 — RefSeq curated summary.

At a glance

• Gene–disease (curated): SOX11-related complex neurodevelopmental disorder with or without congenital anomalies (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 19
• Clinical variants (ClinVar): 450 total — 24 pathogenic, 53 likely-pathogenic
• Phenotypes (HPO): 94
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_003108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11191
Approved symbol	SOX11
Name	SRY-box transcription factor 11
Location	2p25.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176887
Ensembl biotype	protein_coding
OMIM	600898
Entrez	6664

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000322002

RefSeq mRNA: 1 — MANE Select: NM_003108 NM_003108

CCDS: CCDS1654

Canonical transcript exons

ENST00000322002 — 1 exons

Exon	Start	End
ENSE00001282530	5692384	5701385

Expression profiles

Bgee: expression breadth broad, 93 present calls, max score 99.46.

FANTOM5 (CAGE): breadth broad, TPM avg 14.2447 / max 1272.8219, expressed in 642 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18654	10.5464	615
18653	3.2802	380
18656	0.2447	132
18655	0.1425	59
18652	0.0309	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.46	gold quality
cortical plate	UBERON:0005343	99.13	gold quality
embryo	UBERON:0000922	98.54	gold quality
ventricular zone	UBERON:0003053	96.29	gold quality
buccal mucosa cell	CL:0002336	93.44	gold quality
cartilage tissue	UBERON:0002418	90.25	gold quality
cranial nerve II	UBERON:0000941	82.42	gold quality
pigmented layer of retina	UBERON:0001782	73.35	gold quality
medial globus pallidus	UBERON:0002477	65.32	silver quality
nucleus accumbens	UBERON:0001882	63.75	gold quality
hypothalamus	UBERON:0001898	63.26	gold quality
medulla oblongata	UBERON:0001896	62.59	silver quality
ventral tegmental area	UBERON:0002691	62.29	silver quality
entorhinal cortex	UBERON:0002728	62.00	silver quality
amniotic fluid	UBERON:0000173	61.04	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	61.03	gold quality
amygdala	UBERON:0001876	61.01	gold quality
caudate nucleus	UBERON:0001873	60.59	gold quality
inferior olivary complex	UBERON:0002127	60.58	silver quality
temporal lobe	UBERON:0001871	60.43	gold quality
globus pallidus	UBERON:0001875	60.04	silver quality
superior vestibular nucleus	UBERON:0007227	59.61	silver quality
spinal cord	UBERON:0002240	59.09	gold quality
tendon of biceps brachii	UBERON:0008188	58.52	gold quality
dorsal plus ventral thalamus	UBERON:0001897	58.32	silver quality
lateral nuclear group of thalamus	UBERON:0002736	58.29	gold quality
colonic epithelium	UBERON:0000397	58.12	gold quality
Ammon’s horn	UBERON:0001954	58.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	58.09	gold quality
putamen	UBERON:0001874	58.03	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	10921.83
E-MTAB-6911	yes	8709.89
E-MTAB-8894	yes	6078.91
E-GEOD-98556	yes	4994.44
E-MTAB-9154	yes	2886.74
E-HCAD-5	yes	2721.73
E-GEOD-75688	yes	2625.34
E-HCAD-56	yes	2254.07
E-MTAB-10485	yes	1989.16
E-MTAB-9435	yes	1794.00
E-MTAB-11121	yes	1278.09
E-MTAB-10018	yes	688.64
E-HCAD-10	yes	18.42
E-ANND-3	yes	4.27
E-GEOD-93593	no	7067.62

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets.

Target	Regulation
BDNF	Unknown
DBN1	Activation
GDF5	Unknown
HILPDA	Activation
PAX5
PLAGL1	Repression
SETMAR	Activation
SPAST	Activation
TANK	Unknown
TEAD2
TUBB3	Unknown
WNT4	Unknown

Upstream regulators (CollecTRI, top): CHD8

miRNA regulators (miRDB)

310 targeting SOX11, 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-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Sox-11 activates transcription more strongly than Sox-2; the transactivation domain of Sox-11 is primarily responsible for this capability (PMID:12637543)
• Sry transgene resucues sex reversal in C57Bl-Dax1-Y gonads (PMID:15944188)
• two novel mutations in SRY gene in the patients with 46,XY female sex reversal. (PMID:16018252)
• the function of SIP-1/NHERF2 as an SRY cofactor during testis determination is conserved between human and mouse (PMID:16166090)
• The phenotype of the twins presented in this report is consistent with what is generally seen in XX SRY+ males: they have normal genitalia. (PMID:16276109)
• The SRY gene variation was detected in two cases of male infertility. (PMID:17762975)
• specific overexpression of Sox11 mRNA and nuclear protein in both cyclin D1-positive and - negative MCL may be useful for the diagnosis of MCL as a complement to cyclin D1 and also suggests a functional role for Sox11 in MCL. (PMID:17934069)
• the nuclear expression of sox11 is highly associated with mantle cell lymphoma, but is independent of t(11;14)(q13;q32) in non-mantle cell B-cell neoplasms (PMID:19801969)
• Loss of Sox11 is associated with glioma. (PMID:19808959)
• SOX11 mRNA and nuclear protein expression is a highly specific marker for both cyclin D1-positive and negative mantle cell lymphoma (PMID:19880778)
• SOX11 is strongly expressed only in lymphoblastic malignancies and Burkitt’s and mantle cell lymphoma; expression is independent of cyclin D1 (except for weak expression in hairy cell leukemias) and unlikely due to translocations in lymphoid neoplasia. (PMID:19880779)
• Fifteen patients with SOX11-negative tumors exhibited more frequent nonnodal presentation and better survival compared with 97 patients with SOX11-positive MCL (5-year overall survival of 78% versus 36%, respectively; P = 0.001). (PMID:20124476)
• data demonstrate a tumor suppressor function for SOX11 in hematopoietic malignancies and revealed a potential epigenetic regulation of this developmentally involved gene (PMID:20624318)
• Knockdown of Sox11 with siRNA decreased the proliferation and osteogenic differentiation potential of mesenchymal stem cells. (PMID:20626275)
• Expression of SOX11 in mantle cell lymphoma is not only a new diagnostic marker, but may also carry information related to the clinical and biological behavior. (PMID:20919851)
• Data show that DBN1, SETMAR and HIG2 are direct transcriptional targets of the SOX11 protein. (PMID:21124928)
• High expression of SOX11 is associated with mantle cell lymphoma. (PMID:21479697)
• The pathogenic role of SOX11 is associated with its de novo expression in some aggressive lymphoid malignancies, which is mediated by a shift from inactivating to activating histone modifications. (PMID:21738649)
• In vitro studies demonstrated a SOX11-dependent regulation of mantle cell lymphoma - specific gene expression. (PMID:21880559)
• SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. (PMID:21943380)
• SOX11 is useful in differentiating cyclin D1-positive diffuse large B-cell lymphoma from mantle cell lymphoma (PMID:22642745)
• We confirm the importance of SOX11 as a diagnostic antigen in MCL as 100% of tissue micro array (TMA) cases show bright nuclear staining, using the SOX11-C1 antibody in IHC-P. (PMID:22738398)
• Downregulation of SOX11 is associated with neurodevelopmental defects in trisomies 21. (PMID:22752091)
• significant difference between the expression levels of SOX11 in patients with mantle cell lymphoma at diagnosis (n = 21) and in healthy donors (n = 18) (blood: P < 0.0001; marrow: P = 0.0001) (PMID:22827557)
• observations suggest the idea that MCL with mutated IGHV, SOX11-negativity, and nonnodal presentation correspond to a subtype of the disease with more indolent behavior (PMID:22915760)
• There was statistically significant differences in SOX11 mRNA expression between mantle cell lymphoma and other B-cell non-Hodgkin lymphomas. (PMID:22967417)
• SOX11 contributes to tumor development by altering the terminal B-cell differentiation program of mantle cell lymphoma. (PMID:23321250)
• The importance of Sox11 expression as a favourable prognosticator in glioblastomas. (PMID:23619925)
• patients with SOX11 expression showed a shorter TTT and SOX11-expressing MCL patients showed probably a more indolent course, but further analyses within a larger cohort are warranted to prove the independent diagnostic role of SOX11 expression (PMID:23648671)
• SOX11 is overexpressed in cutaneous malignant melanoma patients. (PMID:23867449)
• Characterize the new monoclonal anti-SOX11 antibodies, suitable for Western blot assay and immunohistochemistry. (PMID:24145648)
• SOX11 is not able to identify mantle cell lymphoma from B-cell non-Hodgkin lymphomas (PMID:24225745)
• IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision (PMID:24402778)
• Results show that SOX11 is a potential tumor-suppressor and an independent positive prognostic factor in gastric cancer patients with less advanced clinicopathological features. (PMID:24604109)
• SOX11 directly binds to genes in critical intracellular pathways controlling cell cycle and proliferation in MCL. (PMID:24681958)
• Currently, there are contradictions regarding the association of SOX11 gene expression and outcome in MCL, while some authors have related the lack of SOX11 expression with good prognosis, others find it associated with an adverse clinical course. (PMID:24736261)
• This is the first report stating that quantification of SOX11 can be used as an minimal residual disease marker equal to the key translocation t(11;14) in Mantle cell lymphoma. (PMID:24878000)
• De novo SOX11 mutations cause Coffin-Siris syndrome. Sox11 is expressed in fetal brain and adult brain and heart tissue. (PMID:24886874)
• High nuclear SOX11 expression to be associated with more prolonged overall survival. (PMID:25041022)
• High SOX11 expression is associated with mantle cell lymphoma. (PMID:25056830)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	sox11a	ENSDARG00000077811
mus_musculus	Sox11	ENSMUSG00000063632
rattus_norvegicus	Sox11	ENSRNOG00000030034
drosophila_melanogaster	Sox14	FBGN0005612
drosophila_melanogaster	Sox21a	FBGN0036411
drosophila_melanogaster	Sox102F	FBGN0039938
caenorhabditis_elegans		WBGENE00001182
caenorhabditis_elegans		WBGENE00015716

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), SOX14 (ENSG00000168875), SOX7 (ENSG00000171056), SOX12 (ENSG00000177732), CFAP65 (ENSG00000181378), SOX2 (ENSG00000181449), SOX1 (ENSG00000182968), SRY (ENSG00000184895), SOX18 (ENSG00000203883)

Protein

Protein identifiers

Transcription factor SOX-11 — P35716 (reviewed: P35716)

All UniProt accessions (1): P35716

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that acts as a transcriptional activator. Binds cooperatively with POU3F2/BRN2 or POU3F1/OCT6 to gene promoters, which enhances transcriptional activation. Acts as a transcriptional activator of TEAD2 by binding to its gene promoter and first intron. Plays a redundant role with SOX4 and SOX12 in cell survival of developing tissues such as the neural tube, branchial arches and somites, thereby contributing to organogenesis.

Subcellular location. Nucleus.

Tissue specificity. Expressed primarily in the brain and heart, with low expression in the kidney, pancreas and muscle.

Disease relevance. Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism (IDDMOH) [MIM:615866] An autosomal dominant disorder characterized by developmental delay, impaired intellectual development and microcephaly. Affected individuals may also have oculomotor apraxia, ocular malformations including coloboma, lens abnormalities and microphthalmia, and hypogonadotropic hypogonadism. Some patients may have finger clinodactyly and hypoplastic distal phalanges with nail hypoplasia, especially of the fifth digits. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_003099* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR017386	SOX-12/11/4	Family
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR050140	SRY-related_HMG-box_TF-like	Family

Pfam: PF00505

UniProt features (55 total): sequence variant 39, region of interest 5, compositionally biased region 4, helix 4, chain 1, DNA-binding region 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6T78	X-RAY DIFFRACTION	2.5
6T7A	ELECTRON MICROSCOPY	3.7
6T7C	ELECTRON MICROSCOPY	4
6T7D	ELECTRON MICROSCOPY	4.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35716-F1	58.44	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 206

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 624 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GGGACCA_MIR133A_MIR133B, GOBP_REGULATION_OF_CELL_ACTIVATION, RRAGTTGT_UNKNOWN, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, AAGCAAT_MIR137, GOBP_EPITHELIUM_DEVELOPMENT, chr2p25, ACTACCT_MIR196A_MIR196B, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT

GO Biological Process (43): negative regulation of transcription by RNA polymerase II (GO:0000122), kidney development (GO:0001822), lens morphogenesis in camera-type eye (GO:0002089), outflow tract morphogenesis (GO:0003151), noradrenergic neuron differentiation (GO:0003357), nervous system development (GO:0007399), brain development (GO:0007420), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), oligodendrocyte development (GO:0014003), glial cell proliferation (GO:0014009), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015), spinal cord development (GO:0021510), neuron differentiation (GO:0030182), positive regulation of BMP signaling pathway (GO:0030513), positive regulation of hippo signaling (GO:0035332), skeletal muscle cell differentiation (GO:0035914), positive regulation of neuron differentiation (GO:0045666), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of ossification (GO:0045778), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of hormone secretion (GO:0046887), sympathetic nervous system development (GO:0048485), embryonic digestive tract morphogenesis (GO:0048557), camera-type eye morphogenesis (GO:0048593), embryonic skeletal system morphogenesis (GO:0048704), negative regulation of lymphocyte proliferation (GO:0050672), positive regulation of neurogenesis (GO:0050769), hard palate development (GO:0060022), soft palate development (GO:0060023), negative regulation of glial cell proliferation (GO:0060253), ventricular septum morphogenesis (GO:0060412), lung morphogenesis (GO:0060425), neuroepithelial cell differentiation (GO:0060563), eyelid development in camera-type eye (GO:0061029), cornea development in camera-type eye (GO:0061303), closure of optic fissure (GO:0061386), positive regulation of stem cell proliferation (GO:2000648), negative regulation of transcription regulatory region DNA binding (GO:2000678), positive regulation of lens epithelial cell proliferation (GO:2001111)

GO Molecular Function (8): transcription cis-regulatory region binding (GO:0000976), 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), DNA-binding transcription factor activity (GO:0003700), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA binding (GO:0003677), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
animal organ development	2
anatomical structure morphogenesis	2
neuron differentiation	2
central nervous system development	2
gene expression	2
regulation of gene expression	2
cell differentiation	2
positive regulation of cell differentiation	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
renal system development	1
lens development in camera-type eye	1
camera-type eye morphogenesis	1
heart morphogenesis	1
system development	1
head development	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
glial cell development	1
oligodendrocyte differentiation	1
cell population proliferation	1
gliogenesis	1
transforming growth factor beta receptor signaling pathway	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of cellular response to transforming growth factor beta stimulus	1
anatomical structure development	1
generation of neurons	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
hippo signaling	1
regulation of hippo signaling	1
positive regulation of intracellular signal transduction	1
skeletal muscle tissue development	1
regulation of neuron differentiation	1
osteoblast differentiation	1

Protein interactions and networks

STRING

2068 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SOX11	POU3F3	P20264	649
SOX11	CCND1	P24385	597
SOX11	SMARCA4	P51532	582
SOX11	CD5	P06127	581
SOX11	WT1	P19544	577
SOX11	ARID1B	Q8NFD5	574
SOX11	KLF7	O75840	568
SOX11	ASCL1	P50553	562
SOX11	IGHV4-38-2	P0DP08	544
SOX11	ID2	Q02363	540
SOX11	ARID1A	O14497	533
SOX11	PAX6	P26367	532
SOX11	NEUROG2	Q9H2A3	531
SOX11	POU3F2	P20265	527
SOX11	SOX8	P57073	525

IntAct

10 interactions, top by confidence:

A	B	Type	Score
SOX5	SOX1	psi-mi:“MI:0914”(association)	0.530
H2AC4	H2BC12	psi-mi:“MI:0915”(physical association)	0.530
SOX13	SOX6	psi-mi:“MI:0914”(association)	0.480
SOX11	MTNR1A	psi-mi:“MI:0915”(physical association)	0.370
CCL26	SOX11	psi-mi:“MI:0915”(physical association)	0.370
IL23A	SOX11	psi-mi:“MI:0915”(physical association)	0.370
SOX5	RGPD8	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): SOX11 (Affinity Capture-MS), SOX11 (Two-hybrid), SOX11 (Affinity Capture-MS), SOX11 (Affinity Capture-MS), SOX11 (Affinity Capture-MS), SOX11 (Cross-Linking-MS (XL-MS)), KCNK16 (Cross-Linking-MS (XL-MS)), SOX11 (Affinity Capture-MS), SOX11 (Affinity Capture-MS), SOX11 (Affinity Capture-MS), SOX11 (Affinity Capture-MS), SOX11 (Affinity Capture-RNA)

ESM2 similar proteins: A1Z6W3, A7X8B3, A7X8B7, A7X8C4, B0WAQ0, O97960, P06401, P08155, P09631, P0C1G9, P15619, P23949, P25172, P35716, P40650, P41894, P47974, P48435, P57073, P57074, P78415, P81067, P84550, P84551, Q04886, Q05A36, Q06831, Q06945, Q0V9X5, Q14774, Q15464, Q292U2, Q292U5, Q297V5, Q2VWA4, Q5IS79, Q5U5Q3, Q66JF1, Q6PD21, Q6QT55

Diamond homologs: A0A0G2JTZ2, A2TED3, A5D8R3, B1H349, B3DLD3, B3DM43, F1M8W4, O42342, O42601, P0C1G9, P35710, P35711, P35712, P35713, P35716, P36389, P36390, P36393, P36394, P36396, P40645, P40646, P40647, P40649, P40650, P40656, P40657, P43680, P47792, P48433, P48435, Q03255, Q03257, Q04891, Q05738, Q06831, Q06945, Q20201, Q23045, Q27949

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SOX11	“up-regulates quantity by expression”	SPAST	“transcriptional regulation”
miR-508-5p	“down-regulates quantity by destabilization”	SOX11	“post transcriptional regulation”
CHD8	“down-regulates quantity”	SOX11	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	53
Uncertain significance	223
Likely benign	88
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1344679	NM_003108.4(SOX11):c.191G>A (p.Arg64His)	Pathogenic
139530	NM_003108.4(SOX11):c.178T>C (p.Ser60Pro)	Pathogenic
1527770	GRCh37/hg19 2p25.2(chr2:5449964-6357647)	Pathogenic
1804060	NM_003108.4(SOX11):c.250G>C (p.Gly84Arg)	Pathogenic
2443007	NM_003108.4(SOX11):c.87C>A (p.Cys29Ter)	Pathogenic
2443014	NM_003108.4(SOX11):c.176G>A (p.Trp59Ter)	Pathogenic
2443029	NM_003108.4(SOX11):c.150G>C (p.Lys50Asn)	Pathogenic
2443030	NM_003108.4(SOX11):c.148A>C (p.Lys50Gln)	Pathogenic
2663531	NM_003108.4(SOX11):c.1148dup (p.Gly384fs)	Pathogenic
3235714	NM_003108.4(SOX11):c.1178C>A (p.Ser393Ter)	Pathogenic
3251948	NM_003108.4(SOX11):c.908C>A (p.Ser303Ter)	Pathogenic
3251953	NM_003108.4(SOX11):c.1032_1044del (p.Ser345fs)	Pathogenic
3251954	NM_003108.4(SOX11):c.251G>A (p.Gly84Asp)	Pathogenic
3337352	NM_003108.4(SOX11):c.914_915dup (p.Gly306fs)	Pathogenic
3368249	NM_003108.4(SOX11):c.296T>C (p.Ile99Thr)	Pathogenic
373066	NM_003108.4(SOX11):c.594C>A (p.Tyr198Ter)	Pathogenic
374396	NM_003108.4(SOX11):c.1286G>A (p.Trp429Ter)	Pathogenic
3906864	NM_003108.4(SOX11):c.168C>A (p.Phe56Leu)	Pathogenic
3959939	NM_003108.4(SOX11):c.386C>A (p.Ser129Ter)	Pathogenic
4082044	NM_003108.4(SOX11):c.655_667del (p.Cys219fs)	Pathogenic
420790	NM_003108.4(SOX11):c.190C>G (p.Arg64Gly)	Pathogenic
520896	NM_003108.4(SOX11):c.1164_1176del (p.Asn389fs)	Pathogenic
520936	NM_003108.4(SOX11):c.791C>A (p.Ser264Ter)	Pathogenic
807694	NM_003108.4(SOX11):c.353A>C (p.Tyr118Ser)	Pathogenic
1029671	NM_003108.4(SOX11):c.700G>T (p.Glu234Ter)	Likely pathogenic
1320206	NM_003108.4(SOX11):c.886G>T (p.Glu296Ter)	Likely pathogenic
1332805	NM_003108.4(SOX11):c.239C>T (p.Ser80Phe)	Likely pathogenic
1338785	NM_003108.4(SOX11):c.650_651insGA (p.Lys218fs)	Likely pathogenic
1685451	NM_003108.4(SOX11):c.167T>G (p.Phe56Cys)	Likely pathogenic
1705386	NM_003108.4(SOX11):c.190C>T (p.Arg64Cys)	Likely pathogenic

SpliceAI

340 predictions. Top by Δscore:

Variant	Effect	Δscore
2:5694105:G:GT	donor_gain	0.9900
2:5694259:TG:T	donor_gain	0.9700
2:5694260:GG:G	donor_gain	0.9700
2:5694274:A:AG	donor_gain	0.9600
2:5696343:G:T	donor_gain	0.9500
2:5694271:GAAA:G	donor_gain	0.9300
2:5696280:A:T	donor_gain	0.9300
2:5694274:A:G	donor_gain	0.9100
2:5694264:T:G	donor_gain	0.9000
2:5694279:T:TA	donor_gain	0.8900
2:5694280:A:AA	donor_gain	0.8900
2:5696285:A:T	donor_gain	0.8800
2:5696215:G:GA	donor_gain	0.8600
2:5696291:GTG:G	donor_gain	0.8500
2:5696347:G:GT	donor_gain	0.8300
2:5696293:G:GA	donor_gain	0.8200
2:5696343:G:GT	donor_gain	0.8200
2:5696350:G:GT	donor_gain	0.8200
2:5697357:G:GG	donor_gain	0.8200
2:5694569:G:GT	donor_gain	0.8100
2:5697356:A:AG	donor_gain	0.8100
2:5695704:G:GA	donor_gain	0.7900
2:5696259:TG:T	donor_gain	0.7800
2:5697361:C:G	donor_gain	0.7800
2:5696214:T:TA	donor_gain	0.7700
2:5696288:G:GT	donor_gain	0.7700
2:5697343:G:GT	donor_gain	0.7600
2:5694089:C:G	donor_gain	0.7500
2:5694120:A:AG	donor_gain	0.7500
2:5694264:TTA:T	donor_gain	0.7500

AlphaMissense

2916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:5692842:T:A	W41R	1.000
2:5692842:T:C	W41R	1.000
2:5692844:G:C	W41C	1.000
2:5692844:G:T	W41C	1.000
2:5692845:T:A	C42S	1.000
2:5692845:T:C	C42R	1.000
2:5692846:G:A	C42Y	1.000
2:5692846:G:C	C42S	1.000
2:5692846:G:T	C42F	1.000
2:5692847:C:G	C42W	1.000
2:5692850:G:C	K43N	1.000
2:5692850:G:T	K43N	1.000
2:5692860:G:C	G47R	1.000
2:5692861:G:A	G47D	1.000
2:5692861:G:T	G47V	1.000
2:5692863:C:A	H48N	1.000
2:5692863:C:G	H48D	1.000
2:5692864:A:C	H48P	1.000
2:5692864:A:T	H48L	1.000
2:5692865:C:A	H48Q	1.000
2:5692865:C:G	H48Q	1.000
2:5692866:A:T	I49F	1.000
2:5692867:T:A	I49N	1.000
2:5692867:T:C	I49T	1.000
2:5692867:T:G	I49S	1.000
2:5692869:A:G	K50E	1.000
2:5692870:A:C	K50T	1.000
2:5692870:A:T	K50M	1.000
2:5692871:G:C	K50N	1.000
2:5692871:G:T	K50N	1.000

dbSNP variants (sampled 300 via entrez): RS1000051619 (2:5694379 C>A), RS1000105332 (2:5694628 T>A), RS1000305592 (2:5700001 A>C), RS1001004618 (2:5695764 G>C,T), RS1001063415 (2:5695951 G>A,C), RS1001139499 (2:5701025 G>A), RS1001197304 (2:5696708 G>C), RS1001486046 (2:5701257 C>A), RS1002016460 (2:5696842 T>C), RS1002420651 (2:5696473 C>T), RS1002509282 (2:5691140 C>A), RS1002968805 (2:5691451 G>A), RS1002985921 (2:5691520 A>G), RS1003016513 (2:5697718 C>T), RS1003136889 (2:5693686 A>C)

Disease associations

OMIM: gene MIM:600898 | disease phenotypes: MIM:615866, MIM:147950, MIM:123100, MIM:189800, MIM:135900, MIM:609943, MIM:614562, MIM:300896

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism	Definitive	Autosomal dominant
Coffin-Siris syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
SOX11-related complex neurodevelopmental disorder with or without congenital anomalies	Definitive	AD

Mondo (9): intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism (MONDO:0014376), hypogonadotropic hypogonadism (MONDO:0018555), craniosynostosis (MONDO:0015469), preeclampsia (MONDO:0005081), intellectual disability (MONDO:0001071), Coffin-Siris syndrome 1 (MONDO:0007617), SLC35A2-congenital disorder of glycosylation (MONDO:0010478), Coffin-Siris syndrome (MONDO:0015452), pituitary stalk interruption syndrome (MONDO:0019828)

Orphanet (7): Coffin-Siris syndrome (Orphanet:1465), Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432), Craniosynostosis (Orphanet:1531), Preeclampsia (Orphanet:275555), SLC35A2-CDG (Orphanet:356961), Pituitary stalk interruption syndrome (Orphanet:95496), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

94 total (30 of 94 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000119	Abnormality of the genitourinary system
HP:0000154	Wide mouth
HP:0000179	Thick lower lip vermilion
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000289	Broad philtrum
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000322	Short philtrum
HP:0000331	Short chin
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000430	Underdeveloped nasal alae
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000545	Myopia

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000649_5	Chronic kidney disease	2.000000e-07
GCST001762_495	Obesity-related traits	9.000000e-06
GCST001785_5	Crohn’s disease	4.000000e-09
GCST002198_10	Tuberculosis	7.000000e-07
GCST002900_1	Obesity in adult survivors of childhood cancer exposed to cranial radiation	8.000000e-08
GCST003098_29	Diabetic kidney disease	6.000000e-06
GCST003141_1	Proteinuria and chronic kidney disease	2.000000e-06
GCST004066_135	Hip circumference	9.000000e-06
GCST004066_69	Hip circumference	5.000000e-08
GCST004495_103	BMI (adjusted for smoking behaviour)	2.000000e-13
GCST004497_45	Body mass index (joint analysis main effects and smoking interaction)	1.000000e-12
GCST004499_105	BMI in non-smokers	2.000000e-12
GCST005580_300	Intraocular pressure	3.000000e-09
GCST007329_24	Automobile speeding propensity	2.000000e-08
GCST007329_27	Automobile speeding propensity	3.000000e-08
GCST008833_10	Type 2 diabetes	6.000000e-08
GCST012332_51	Multisite chronic pain	3.000000e-08
GCST012334_3	Multisite chronic pain	2.000000e-08
GCST90000050_9	Age at first birth	2.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005109	energy expenditure
EFO:0004318	smoking behavior
EFO:0004340	body mass index
EFO:0004695	intraocular pressure measurement
EFO:0008579	risk-taking behaviour
EFO:0010100	multisite chronic pain
EFO:0009101	age at first birth measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D011225	Pre-Eclampsia	C12.050.703.395.249
C536436	Coffin-Siris syndrome (supp.)

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
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	10
trichostatin A	affects cotreatment, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
arsenite	increases methylation	1
hydroquinone	decreases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Camptothecin	increases methylation	1
Cisplatin	affects expression	1
Estradiol	affects cotreatment, decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Progesterone	affects cotreatment, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases abundance, decreases expression	1

Cellosaurus cell lines

7 cell lines: 5 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A6L4	SEES3-1V human SOX11, clone1	Embryonic stem cell	Male
CVCL_A6L5	SEES3-1V human SOX11, clone2	Embryonic stem cell	Male
CVCL_A6L6	SEES3-1V human SOX11, clone3	Embryonic stem cell	Male
CVCL_B8PX	Abcam HCT 116 SOX11 KO	Cancer cell line	Male
CVCL_B9SD	Abcam A-549 SOX11 KO	Cancer cell line	Male
CVCL_E6IC	HUES6 SOX11 ES.HET1	Embryonic stem cell	Female
CVCL_E6ID	HUES6 SOX11 ES.HET2	Embryonic stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00328926	PHASE4	TERMINATED	Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT01454011	PHASE4	COMPLETED	The Effect of Testosterone Replacement on the High Density Lipoprotein Cholesterol Subgroups
NCT01601327	PHASE4	COMPLETED	Effects of Medications in Patients With Hypogonadism
NCT02310074	PHASE4	UNKNOWN	Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03490513	PHASE4	COMPLETED	Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism
NCT04456296	PHASE4	COMPLETED	A Study of the Effect of Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism
NCT05205837	PHASE4	TERMINATED	A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36