SCAF4

Chr 21AD

SR-related CTD associated factor 4

Also known as: FZS, SFRS15, SRA4

NCBI Gene: 57466ENSG00000156304UniProt: O95104

This gene likely encodes a member of the arginine/serine-rich splicing factor family. A similar protein in Rat appears to bind the large subunit of RNA polymerase II and provide a link between transcription and pre-mRNA splicing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

Primary Disease Associations & Inheritance

Fliedner-Zweier syndromeMIM #620511
AD
0
Active trials
97
Pathogenic / LP
384
ClinVar variants
7
Pubs (1 yr)
1.9
Missense Z
0.11
LOEUF· LoF intolerant
Clinical Summary— SCAF4
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
97 Pathogenic / Likely Pathogenic· 237 VUS of 384 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 6.92
OE 0.03 (0.01–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.94Z-score
OE missense 0.79 (0.73–0.85)
518 obs / 658.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.03 (0.01–0.11)
0≤0.351.4
Missense OE0.79 (0.73–0.85)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 2 / 59.6Missense obs/exp: 518 / 658.2Syn Z: -0.89
LOF
DN
0.2199th %ile
GOF
0.2696th %ile
LOF
0.87top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 25% of P/LP variants are LoF · LOEUF 0.11

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

384 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic80
Likely Pathogenic17
VUS237
Likely Benign47
Benign1
Conflicting2
80
Pathogenic
17
Likely Pathogenic
237
VUS
47
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
1
65
0
80
Likely Pathogenic
10
1
6
0
17
VUS
9
203
24
1
237
Likely Benign
1
31
8
7
47
Benign
0
0
0
1
1
Conflicting
—2
Total342361039384

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

SCAF4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SCAF4-related neurodevelopmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients