TMEM59

Chr 1

transmembrane protein 59

Also known as: C1orf8, DCF1, HSPC001, PRO195, UNQ169

NCBI Gene: 9528ENSG00000116209UniProt: Q9BXS4OMIM: 617084

This gene encodes a protein that regulates autophagy in response to bacterial infections and modulates protein glycosylation in the Golgi apparatus, including processing of amyloid precursor protein. The gene shows very low constraint against loss-of-function variants (pLI nearly zero, LOEUF 1.47), but no established human disease associations have been reported in the provided data. Clinical significance of TMEM59 variants in pediatric patients remains undefined.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.47
Clinical Summary— TMEM59
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 34 VUS of 54 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
1.47LOEUF
pLI 0.000
Z-score 0.04
OE 0.99 (0.68–1.47)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.44Z-score
OE missense 0.90 (0.79–1.03)
151 obs / 166.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.99 (0.68–1.47)
0≤0.351.4
Missense OE0.90 (0.79–1.03)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 18 / 18.2Missense obs/exp: 151 / 166.9Syn Z: 0.23
DN
0.4983th %ile
GOF
0.6737th %ile
LOF
0.4038th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

54 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS34
9
Pathogenic
3
Likely Pathogenic
34
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
3
0
3
VUS
0
30
4
0
34
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total03016046

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM59 · 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