RESF1

Chr 12

retroelement silencing factor 1

Also known as: C12orf35, GET, KIAA1551, UTA2-1

NCBI Gene: 55196ENSG00000174718UniProt: Q9HCM1

The RESF1 protein regulates imprinted gene expression and maintains repressive chromatin modifications by recruiting SETDB1 to silence endogenous retroviruses in embryonic stem cells. Mutations cause neurodevelopmental disorders with autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants, indicating that complete protein loss is likely incompatible with normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
33
P/LP submissions
0%
P/LP missense
0.41
LOEUF
—
Mechanism
Clinical Summary— RESF1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 305 VUS of 388 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.009
Z-score 5.23
OE 0.27 (0.18–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-1.79Z-score
OE missense 1.17 (1.11–1.24)
1005 obs / 857.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.27 (0.18–0.41)
0≤0.351.4
Missense OE1.17 (1.11–1.24)
0≤0.61.4
Synonymous OE1.11
0≤1.21.6
LoF obs/exp: 16 / 59.6Missense obs/exp: 1005 / 857.4Syn Z: -1.52

ClinVar Variant Classifications

388 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic3
VUS305
Likely Benign32
Benign3
30
Pathogenic
3
Likely Pathogenic
305
VUS
32
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
3
0
3
VUS
0
303
2
0
305
Likely Benign
0
30
0
2
32
Benign
0
2
0
1
3
Total0335353373

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

View in ClinVar →

Protein Context — Lollipop Plot

RESF1 · 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.

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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
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