TMEM105

Chr 17

TMEM105 long non-coding RNA

NCBI Gene: 284186ENSG00000185332UniProt: Q8N8V8

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
18
Pathogenic / LP
21
ClinVar variants
3
Pubs (1 yr)
-0.1
Missense Z
1.94
LOEUF
Clinical Summary— TMEM105
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 2 VUS of 21 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.
1.94LOEUF
pLI 0.014
Z-score -0.82
OE 1.85 (0.51–1.94)
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.
-0.14Z-score
OE missense 1.05 (0.87–1.26)
80 obs / 76.6 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.1.85 (0.51–1.94)
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 (0.87–1.26)
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.1.09
0≤1.21.6
LoF obs/exp: 2 / 1.1Missense obs/exp: 80 / 76.6Syn Z: -0.41
DN
0.74top 25%
GOF
0.6638th %ile
LOF
0.4234th %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

21 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic2
VUS2
Likely Benign1
16
Pathogenic
2
Likely Pathogenic
2
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————16
Likely Pathogenic
————2
VUS
————2
Likely Benign
————1
Benign
————0
Total—21

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TMEM105 · 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
TMEM105 upregulation promotes colorectal cancer malignancy: a novel prognostic biomarker potentially linked to the MYC-Ribosome biogenesis axis
Rezaenasab A et al.·Cancer Cell Int
2026
Machine learning-mediated identification of ferroptosis-related genes in osteonecrosis of the femoral head
Huang X et al.·FEBS Open Bio
2024
Evolutionary learning-derived lncRNA signature with biomarker discovery for predicting stage of colon adenocarcinoma.
Ho YL et al.·Annu Int Conf IEEE Eng Med Biol Soc
2024
Development and Validation of Ferroptosis- and Immune-Related lncRNAs Signatures for Breast Infiltrating Duct and Lobular Carcinoma
Wei T et al.·Front Oncol
2022
C10orf55, CASC2, and SFTA1P lncRNAs Are Potential Biomarkers to Assess Radiation Therapy Response in Head and Neck Cancers
Paszkowska A et al.·J Pers Med
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 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