SCAF8

Chr 6

SR-related CTD associated factor 8

Also known as: RBM16

NCBI Gene: 22828 ENSG00000213079 UniProt: Q9UPN6 OMIM: 616024

The SCAF8 protein prevents premature termination of RNA polymerase II transcription by binding to nascent RNA and suppressing early polyadenylation sites, thereby ensuring production of full-length functional proteins. Mutations cause autosomal dominant neurodevelopmental disorder with microcephaly, epilepsy, and brain malformations. This gene is highly constrained against loss-of-function variants, reflecting its critical role in normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity and RNA polymerase II C-terminal domain phosphoserine binding activity. Involved in negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled and positive regulation of DNA-templated transcription, elongation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.10

Clinical Summary— SCAF8

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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.

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ClinVar Variants

144 VUS of 175 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.10LOEUF

pLI 1.000

Z-score 7.27

OE 0.03 (0.01–0.10)

Highly constrained

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

Missense Constraint?

1.90Z-score

OE missense 0.80 (0.74–0.86)

560 obs / 701.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.10)

0≤0.351.4

Missense OE?0.80 (0.74–0.86)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 2 / 65.5Missense obs/exp: 560 / 701.5Syn Z: -2.62

This gene — mechanism propensity

0.2698th %ile

GOF

0.2497th %ile

LOF

0.84top 5%

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

LOFprediction above median · LOEUF 0.10

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

175 submitted variants in ClinVar

ClinVar

Classification Summary

VUS144

Likely Benign6

144

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	142	1	144
Likely Benign	1	5	0	6
Benign	0	0	0	0
Total	2	147	1	150

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap SCAF8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →