TMEM94

Chr 17AR

transmembrane protein 94

Also known as: ERMA, IDDCDF, KIAA0195

NCBI Gene: 9772 ENSG00000177728 UniProt: Q12767 OMIM: 618163

TMEM94 encodes a P-type magnesium transporter that transports magnesium ions from the cytosol into the endoplasmic reticulum. Biallelic mutations cause autosomal recessive intellectual developmental disorder with cardiac defects and dysmorphic facies. This gene is highly constrained against loss-of-function variants, indicating it is essential for normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.641 OMIM phenotype

Clinical Summary— TMEM94

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Gene-Disease Validity (ClinGen)

intellectual developmental disorder with cardiac defects and dysmorphic facies · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

24 unique Pathogenic / Likely Pathogenic· 209 VUS of 326 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 4.07

OE 0.48 (0.37–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

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?

LoF OE?0.48 (0.37–0.64)

0≤0.351.4

Missense OE?0.75 (0.70–0.81)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 35 / 72.4Missense obs/exp: 619 / 820.9Syn Z: 0.65

ClinVar Variant Classifications

326 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic15

VUS209

Likely Benign53

Benign5

Pathogenic

Likely Pathogenic

209

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	0	1	0	9
Likely Pathogenic	15	0	0	0	15
VUS	7	198	3	1	209
Likely Benign	0	14	6	33	53
Benign	0	2	1	2	5
Total	30	214	11	36	291

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap TMEM94 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →