TMEM94

Chr 17AR

transmembrane protein 94

Also known as: ERMA, IDDCDF, KIAA0195

NCBI Gene: 9772ENSG00000177728UniProt: Q12767

Enables P-type magnesium transporter activity. Involved in magnesium ion transport from cytosol to endoplasmic reticulum. Is active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Intellectual developmental disorder with cardiac defects and dysmorphic faciesMIM #618316
AR
307
ClinVar variants
35
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TMEM94
🧬
Gene-Disease Validity (ClinGen)
intellectual developmental disorder with cardiac defects and dysmorphic facies · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 Pathogenic / Likely Pathogenic· 214 VUS of 307 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.
0.64LOEUF
pLI 0.000
Z-score 4.07
OE 0.48 (0.37–0.64)
Tolerant

Typical tolerance to LoF variation

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.
2.50Z-score
OE missense 0.75 (0.70–0.81)
619 obs / 820.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.48 (0.37–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.70–0.81)
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.0.96
0≤1.21.6
LoF obs/exp: 35 / 72.4Missense obs/exp: 619 / 820.9Syn Z: 0.65

ClinVar Variant Classifications

307 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic13
VUS214
Likely Benign53
Benign5
22
Pathogenic
13
Likely Pathogenic
214
VUS
53
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
16
0
22
Likely Pathogenic
9
0
4
0
13
VUS
5
194
14
1
214
Likely Benign
0
14
6
33
53
Benign
0
2
1
2
5
Total202104136307

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM94 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TMEM94-related neurodevelopmental delay, congenital heart defects, and distinct facial dysmorphism

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder with cardiac defects and dysmorphic facies

MIM #618316

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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