ZNF683

Chr 1

zinc finger protein 683

Also known as: Hobit

NCBI Gene: 257101ENSG00000176083UniProt: Q8IZ20OMIM: 616775

ZNF683 encodes a transcription factor that regulates gene expression in tissue-resident immune cells including memory T cells, natural killer cells, and NKT cells, controlling their retention in non-lymphoid organs like skin, gut, liver and kidney. Mutations cause primary immunodeficiency with early-onset severe infections. The gene shows very low constraint to loss-of-function variation, suggesting tolerance to protein loss.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.34
Clinical Summary— ZNF683
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 85 VUS of 105 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
1.34LOEUF
pLI 0.000
Z-score 0.61
OE 0.83 (0.53–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.10Z-score
OE missense 1.02 (0.92–1.12)
284 obs / 279.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.83 (0.53–1.34)
0≤0.351.4
Missense OE1.02 (0.92–1.12)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 12 / 14.5Missense obs/exp: 284 / 279.3Syn Z: 0.70
DN
0.6647th %ile
GOF
0.5072th %ile
LOF
0.57top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
VUS85
Likely Benign8
5
Pathogenic
85
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
0
0
0
VUS
0
79
6
0
85
Likely Benign
0
6
0
2
8
Benign
0
0
0
0
0
Total08511298

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF683 · 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 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