TMEM225

Chr 11

transmembrane protein 225

Also known as: PMP22CD, PPP1R154, SPATA47

NCBI Gene: 338661ENSG00000204300UniProt: Q6GV28

TMEM225 encodes a protein that inhibits protein phosphatase 1 (PP1) in sperm by binding to the catalytic subunit PPP1CC and is located in acrosomal membranes. Based on the available data, no specific diseases have been definitively associated with mutations in this gene. The gene shows low constraint against loss-of-function variants (pLI 0.002, LOEUF 1.42), suggesting tolerance to such mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
53
P/LP submissions
0%
P/LP missense
1.42
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— TMEM225
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 unique Pathogenic / Likely Pathogenic· 31 VUS of 92 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
1.42LOEUF
pLI 0.002
Z-score 0.80
OE 0.68 (0.35–1.42)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.34Z-score
OE missense 0.91 (0.78–1.07)
111 obs / 121.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.35–1.42)
0≤0.351.4
Missense OE0.91 (0.78–1.07)
0≤0.61.4
Synonymous OE1.18
0≤1.21.6
LoF obs/exp: 5 / 7.3Missense obs/exp: 111 / 121.5Syn Z: -0.95
DN
0.82top 10%
GOF
0.73top 25%
LOF
0.1697th %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

92 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic2
VUS31
Likely Benign6
51
Pathogenic
2
Likely Pathogenic
31
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
51
0
51
Likely Pathogenic
0
0
2
0
2
VUS
0
28
3
0
31
Likely Benign
0
6
0
0
6
Benign
0
0
0
0
0
Total03456090

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM225 · 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
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 2 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