SURF6

Chr 9

surfeit 6

Also known as: RRP14

NCBI Gene: 6838ENSG00000148296UniProt: O75683OMIM: 185642

The protein binds to DNA and RNA and functions as a nucleolar matrix protein involved in ribosomal biosynthesis or assembly. Mutations cause neurodevelopmental disorder with seizures, intellectual disability, and dysmorphic features, which follows an autosomal recessive inheritance pattern. The gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.13
Clinical Summary— SURF6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 88 VUS of 133 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 1.18
OE 0.69 (0.44–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.27Z-score
OE missense 1.05 (0.95–1.17)
253 obs / 241.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.69 (0.44–1.13)
0≤0.351.4
Missense OE1.05 (0.95–1.17)
0≤0.61.4
Synonymous OE1.22
0≤1.21.6
LoF obs/exp: 12 / 17.3Missense obs/exp: 253 / 241.1Syn Z: -1.75
DN
0.6743th %ile
GOF
0.6735th %ile
LOF
0.2775th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

133 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic1
VUS88
Likely Benign3
35
Pathogenic
1
Likely Pathogenic
88
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
1
0
1
VUS
1
79
8
0
88
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total181441127

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

View in ClinVar →

Protein Context — Lollipop Plot

SURF6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
KRAS mutations promote the intratumoral colonization of enterotoxigenic bacteroides fragilis in colorectal cancer through the regulation of the miRNA3655/SURF6/IRF7/IFNβ axis.
Chen Y et al.·Gut Microbes
2024Open Access
Human nucleolar protein SURF6/RRP14 participates in early steps of pre-rRNA processing.
Moraleva A et al.·PLoS One
2023Open Access
A Higher Level of Expression of the Nucleolar Protein SURF6 in Human Normal Activated Lymphocytes and in Lymphocytes of Patients with Lymphoproliferative Disorders.
Moraleva AA et al.·Dokl Biochem Biophys
2020Cohort
Compositional adaptability in NPM1-SURF6 scaffolding networks enabled by dynamic switching of phase separation mechanisms.
Ferrolino MC et al.·Nat Commun
2018Open AccessFunctional
Involvement of the specific nucleolar protein SURF6 in regulation of proliferation and ribosome biogenesis in mouse NIH/3T3 fibroblasts.
Moraleva A et al.·Cell Cycle
2017Functional
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