SF3B4-related acrofacial dysostosis

Summary

SF3B4-related acrofacial dysostosis (MONDO:0800483) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	SF3B4-related acrofacial dysostosis
Mondo ID	MONDO:0800483
GARD	0026574
Is cancer (heuristic)	no

Also known as: SF3B4-related acrofacial dysostosis

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › acrofacial dysostosis › SF3B4-related acrofacial dysostosis

Related subtypes (13): acrofacial dysostosis, Catania type, Patterson-Stevenson-Fontaine syndrome, acrofacial dysostosis, Weyers type, acrocraniofacial dysostosis, acrofacial dysostosis Rodriguez type, acrofrontofacionasal dysostosis, postaxial acrofacial dysostosis, acrofacial dysostosis, Palagonia type, acromelic frontonasal dysostosis, mandibulofacial dysostosis-microcephaly syndrome, acrofacial dysostosis Cincinnati type, acrofacial dysostosis, Kennedy-Teebi type, acrofacial dysostosis Preis type

Subtypes (1): Nager acrofacial dysostosis

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3780598	NM_005850.5(SF3B4):c.913+5G>T	SF3B4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SF3B4	Orphanet:1788	Acrofacial dysostosis, Rodríguez type
SF3B4	Orphanet:245	Nager 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
SF3B4	HGNC:10771	ENSG00000143368	Q15427	Splicing factor 3B subunit 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SF3B4	Splicing factor 3B subunit 4	Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SF3B4	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, SF3B4_RRM1

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
granulocyte	1
mucosa of transverse colon	1
transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SF3B4	259	ubiquitous	marker	mucosa of transverse colon, transverse colon, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SF3B4	3,119

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SF3B4	Q15427	45

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
mRNA Splicing - Minor Pathway	1	223.9×	0.019	SF3B4
mRNA Splicing	1	109.8×	0.019	SF3B4
CHD1 and CHD2 subfamily	1	108.8×	0.019	SF3B4
mRNA Polyadenylation	1	87.8×	0.019	SF3B4
Processing of Capped Intron-Containing Pre-mRNA	1	82.2×	0.019	SF3B4
mRNA Splicing - Major Pathway	1	54.6×	0.024	SF3B4
Dengue Virus-Host Interactions	1	45.7×	0.024	SF3B4
Metabolism of RNA	1	41.7×	0.024	SF3B4

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
RNA splicing, via transesterification reactions	1	624.1×	0.004	SF3B4
U2-type prespliceosome assembly	1	624.1×	0.004	SF3B4
mRNA splicing, via spliceosome	1	91.6×	0.013	SF3B4
RNA splicing	1	88.2×	0.013	SF3B4
mRNA processing	1	78.8×	0.013	SF3B4

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SF3B4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SF3B4	6	Binding:6

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	SF3B4

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)
SF3B4	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.