TMEM95

Chr 17

transmembrane protein 95

Also known as: UNQ9390

NCBI Gene: 339168ENSG00000182896UniProt: Q3KNT9

Involved in fusion of sperm to egg plasma membrane involved in single fertilization. Predicted to be located in cytoplasmic vesicle and sperm plasma membrane. Predicted to be active in acrosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

67
ClinVar variants
29
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TMEM95
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 38 VUS of 67 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.
1.55LOEUF
pLI 0.000
Z-score 0.12
OE 0.96 (0.62–1.55)
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.
-0.23Z-score
OE missense 1.06 (0.91–1.25)
107 obs / 100.6 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.0.96 (0.62–1.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.91–1.25)
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.0.93
0≤1.21.6
LoF obs/exp: 12 / 12.4Missense obs/exp: 107 / 100.6Syn Z: 0.36

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic3
VUS38
26
Pathogenic
3
Likely Pathogenic
38
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
3
0
3
VUS
0
32
6
0
38
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total03235067

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM95 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Human sperm TMEM95 binds eggs and facilitates membrane fusion.
Tang S et al.·Proc Natl Acad Sci U S A
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The Role of Sperm Proteins IZUMO1 and TMEM95 in Mammalian Fertilization: A Systematic Review.
Hernández-Falcó M et al.·Int J Mol Sci
2022🔓 Open AccessReview
TMEM95 is a sperm membrane protein essential for mammalian fertilization.
Lamas-Toranzo I et al.·Elife
2020🔓 Open Access
Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice.
Noda T et al.·Proc Natl Acad Sci U S A
2020🔓 Open Access
Detection of Bovine TMEM95 p.Cys161X Mutation in 13 Chinese Indigenous Cattle Breeds.
Zhang S et al.·Animals (Basel)
2019🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools