SURF6

Chr 9

surfeit 6

Also known as: RRP14

NCBI Gene: 6838ENSG00000148296UniProt: O75683

This gene encodes a conserved protein that is localized to the nucleolus. The encoded protein may function as a nucleolar-matrix protein with nucleic acid-binding properties. There is a pseudogene for this gene on chromosome Y. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

0
Active trials
36
Pathogenic / LP
127
ClinVar variants
1
Pubs (1 yr)
-0.3
Missense Z
1.13
LOEUF
Clinical Summary— SURF6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 88 VUS of 127 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.27Z-score
OE missense 1.05 (0.95–1.17)
253 obs / 241.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.44–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.95–1.17)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
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

127 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.

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 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