TMEM245

Chr 9

transmembrane protein 245

Also known as: C9orf5, CG-2, CG2

NCBI Gene: 23731ENSG00000106771UniProt: Q9H330OMIM: 620252

The protein is predicted to be located in membrane structures, but its specific cellular function remains unknown. Mutations in TMEM245 cause neurodevelopmental disorders through a predicted dominant-negative mechanism. The inheritance pattern and specific clinical phenotypes associated with TMEM245 mutations are not established based on the available data.

OMIMResearchSummary from RefSeq, Mechanism
MultiplemechanismLOEUF 0.59
Clinical Summary— TMEM245
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 125 VUS of 200 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 3.68
OE 0.40 (0.27–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.24Z-score
OE missense 0.83 (0.76–0.91)
354 obs / 426.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.40 (0.27–0.59)
0≤0.351.4
Missense OE0.83 (0.76–0.91)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 17 / 43.0Missense obs/exp: 354 / 426.2Syn Z: -1.71
DN
0.78top 25%
GOF
0.73top 25%
LOF
0.2873th %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

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic5
VUS125
Likely Benign7
Benign1
30
Pathogenic
5
Likely Pathogenic
125
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
5
0
5
VUS
0
118
7
0
125
Likely Benign
0
4
0
3
7
Benign
0
0
0
1
1
Total0122424168

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM245 · 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 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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