Coffin-Siris syndrome 10

Summary

Coffin-Siris syndrome 10 (MONDO:0032791) is a disease caused by SOX4 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SOX4 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 44

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Coffin-Siris syndrome 10
Mondo ID	MONDO:0032791
OMIM	618506
DOID	DOID:0112371
UMLS	C4760583
MedGen	1683634
GARD	0016358
Is cancer (heuristic)	no

Also known as: CSS10

Data availability: 44 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Coffin-Siris syndrome › Coffin-Siris syndrome 10

Related subtypes (10): Coffin-Siris syndrome 1, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, Coffin-Siris syndrome 5, Coffin-Siris syndrome 12, Coffin-Siris syndrome 8, Coffin-Siris syndrome 11, Coffin-Siris syndrome 7

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

44 retrieved; paginated sample, class counts are floors:

20 uncertain significance, 9 likely pathogenic, 6 pathogenic, 4 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1220547	NM_003107.3(SOX4):c.1040C>A (p.Ser347Ter)	SOX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686223	NM_003107.3(SOX4):c.975C>G (p.Tyr325Ter)	SOX4	Pathogenic	criteria provided, single submitter
2443795	NM_003107.3(SOX4):c.1333G>T (p.Glu445Ter)	SOX4	Pathogenic	criteria provided, single submitter
2443796	NM_003107.3(SOX4):c.130_133delinsCGCT (p.Gly44_Lys45delinsArgTer)	SOX4	Pathogenic	no assertion criteria provided
3254650	NM_003107.3(SOX4):c.386_390del (p.Arg129fs)	SOX4	Pathogenic	criteria provided, single submitter
4074737	NM_003107.3(SOX4):c.1274C>A (p.Ser425Ter)	SOX4	Pathogenic	criteria provided, single submitter
4795244	NM_003107.3(SOX4):c.468_469del (p.Asp156fs)	SOX4	Pathogenic	criteria provided, single submitter
635852	NM_003107.3(SOX4):c.334G>C (p.Ala112Pro)	SOX4	Pathogenic/Likely pathogenic	no assertion criteria provided
635853	NM_003107.3(SOX4):c.176T>G (p.Ile59Ser)	SOX4	Pathogenic/Likely pathogenic	no assertion criteria provided
635854	NM_003107.3(SOX4):c.315G>T (p.Lys105Asn)	SOX4	Pathogenic/Likely pathogenic	no assertion criteria provided
2580163	NM_003107.3(SOX4):c.281G>A (p.Gly94Asp)	SOX4	Likely pathogenic	criteria provided, single submitter
2664011	NM_003107.3(SOX4):c.373_378del (p.Asp125_Tyr126del)	SOX4	Likely pathogenic	no assertion criteria provided
3254652	NM_003107.3(SOX4):c.335C>A (p.Ala112Glu)	SOX4	Likely pathogenic	criteria provided, single submitter
3392529	NM_003107.3(SOX4):c.200T>C (p.Met67Thr)	SOX4	Likely pathogenic	criteria provided, single submitter
3629480	NM_003107.3(SOX4):c.185C>T (p.Pro62Leu)	SOX4	Likely pathogenic	criteria provided, single submitter
3774374	NM_003107.3(SOX4):c.185C>G (p.Pro62Arg)	SOX4	Likely pathogenic	criteria provided, single submitter
4279018	NM_003107.3(SOX4):c.251T>G (p.Met84Arg)	SOX4	Likely pathogenic	criteria provided, single submitter
4813418	NM_003107.3(SOX4):c.332dup (p.Ala112fs)	SOX4	Likely pathogenic	criteria provided, single submitter
548142	NM_003107.3(SOX4):c.198C>A (p.Phe66Leu)	SOX4	Likely pathogenic	criteria provided, single submitter
1341848	NM_003107.3(SOX4):c.499_500insCGG (p.His166_Gly167insAla)	SOX4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2656272	NM_003107.3(SOX4):c.666CGG[6] (p.Gly227_Lys228insGly)	SOX4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
931190	NM_003107.3(SOX4):c.697_708del (p.Ala233_Ser236del)	SOX4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2583138	NM_003107.3(SOX4):c.965delinsAGGG (p.Leu322delinsGlnGly)	LOC129995966	Uncertain significance	criteria provided, single submitter
1029670	NM_003107.3(SOX4):c.746C>A (p.Pro249His)	SOX4	Uncertain significance	criteria provided, single submitter
1285590	NM_003107.3(SOX4):c.193G>A (p.Ala65Thr)	SOX4	Uncertain significance	criteria provided, single submitter
1333895	NM_003107.3(SOX4):c.1382A>T (p.Asp461Val)	SOX4	Uncertain significance	criteria provided, single submitter
1341908	NM_003107.3(SOX4):c.149G>C (p.Ser50Thr)	SOX4	Uncertain significance	criteria provided, single submitter
1526184	NM_003107.3(SOX4):c.173A>C (p.His58Pro)	SOX4	Uncertain significance	criteria provided, single submitter
2436258	NM_003107.3(SOX4):c.618_626del (p.204AGG[1])	SOX4	Uncertain significance	criteria provided, single submitter
2443346	NM_003107.3(SOX4):c.362C>G (p.Ala121Gly)	SOX4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SOX4	Strong	Autosomal dominant	Coffin-Siris syndrome 10	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOX4	Orphanet:1465	Coffin-Siris syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SOX4	HGNC:11200	ENSG00000124766	Q06945	Transcription factor SOX-4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SOX4	Transcription factor SOX-4	Transcriptional activator that binds with high affinity to the T-cell enhancer motif 5’-AACAAAG-3’ motif.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SOX4	Transcription factor	no		HMG_box_dom, SOX-12/11/4, HMG_box_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
embryo	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SOX4	295	ubiquitous	marker	cortical plate, ganglionic eminence, embryo

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOX4	2,846

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SOX4	Q06945	55.71

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Deactivation of the beta-catenin transactivating complex	1	233.1×	0.012	SOX4
TCF dependent signaling in response to WNT	1	117.7×	0.012	SOX4
Signaling by WNT	1	112.0×	0.012	SOX4
Signal Transduction	1	10.2×	0.098	SOX4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glial cell development	1	5617.3×	0.002	SOX4
pro-B cell differentiation	1	4213.0×	0.002	SOX4
ascending aorta morphogenesis	1	4213.0×	0.002	SOX4
atrial septum primum morphogenesis	1	3370.4×	0.002	SOX4
noradrenergic neuron differentiation	1	2407.4×	0.002	SOX4
mesenchyme development	1	2407.4×	0.002	SOX4
regulation of DNA damage response, signal transduction by p53 class mediator	1	2106.5×	0.002	SOX4
positive regulation of gamma-delta T cell differentiation	1	1872.4×	0.002	SOX4
kidney morphogenesis	1	1872.4×	0.002	SOX4
mitral valve morphogenesis	1	1685.2×	0.002	SOX4
neuroepithelial cell differentiation	1	1532.0×	0.002	SOX4
cardiac right ventricle morphogenesis	1	1404.3×	0.002	SOX4
endocrine pancreas development	1	936.2×	0.003	SOX4
sympathetic nervous system development	1	936.2×	0.003	SOX4
glial cell proliferation	1	887.0×	0.003	SOX4
camera-type eye morphogenesis	1	766.0×	0.003	SOX4
negative regulation of myoblast differentiation	1	624.1×	0.004	SOX4
hematopoietic stem cell homeostasis	1	561.7×	0.004	SOX4
spinal cord development	1	510.7×	0.004	SOX4
ventricular septum morphogenesis	1	432.1×	0.005	SOX4
T cell differentiation	1	383.0×	0.005	SOX4
positive regulation of myoblast differentiation	1	366.4×	0.005	SOX4
cellular response to glucose stimulus	1	267.5×	0.006	SOX4
positive regulation of insulin secretion	1	255.3×	0.006	SOX4
somatic stem cell population maintenance	1	247.8×	0.006	SOX4
positive regulation of canonical Wnt signaling pathway	1	154.6×	0.010	SOX4
glucose homeostasis	1	130.6×	0.011	SOX4
neuron differentiation	1	100.3×	0.014	SOX4
gene expression	1	79.9×	0.016	SOX4
brain development	1	79.5×	0.016	SOX4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SOX4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SOX4

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SOX4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.