TMEM240

Chr 1AD

transmembrane protein 240

Also known as: C1orf70, SCA21

NCBI Gene: 339453ENSG00000205090UniProt: Q5SV17OMIM: 616101

The protein is a transmembrane domain-containing protein expressed in the brain and cerebellum. Mutations cause spinocerebellar ataxia 21, a progressive neurodegenerative disorder primarily affecting cerebellar function and coordination. This condition follows autosomal dominant inheritance.

OMIMResearchSummary from RefSeq, OMIM
LOFmechanismADLOEUF 0.871 OMIM phenotype
Clinical Summary— TMEM240
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
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ClinVar Variants
135 unique Pathogenic / Likely Pathogenic· 97 VUS of 311 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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
0.87LOEUF
pLI 0.229
Z-score 1.80
OE 0.28 (0.11–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.55Z-score
OE missense 0.58 (0.47–0.72)
62 obs / 107.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.11–0.87)
0≤0.351.4
Missense OE0.58 (0.47–0.72)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 2 / 7.2Missense obs/exp: 62 / 107.0Syn Z: -0.55
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTMEM240-related spinocerebellar ataxia and intellectual disabilityLOFAD
DN
0.6939th %ile
GOF
0.78top 25%
LOF
0.3745th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

311 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic126
Likely Pathogenic9
VUS97
Likely Benign53
Benign17
Conflicting8
126
Pathogenic
9
Likely Pathogenic
97
VUS
53
Likely Benign
17
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
125
0
126
Likely Pathogenic
0
2
7
0
9
VUS
5
67
25
0
97
Likely Benign
0
5
19
29
53
Benign
0
1
10
6
17
Conflicting
—8
Total67518635310

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM240 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
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