TMEM199

Chr 17AR

vacuolar ATPase assembly factor VMA12

Also known as: C17orf32, CDG2P, TMEM199, VPH2

NCBI Gene: 147007UniProt: Q8N511

The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) in some human cells. The encoded protein shares some homology with the yeast protein Vma12. Defects in this gene are a cause of congenital disorder of glycosylation, type IIp. [provided by RefSeq, Mar 2016]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IIpMIM #616829
AR
Congenital disorder of glycosylation, type IIpMIM #616829
AR
0
Active trials
1
Pathogenic / LP
18
ClinVar variants
1
Pubs (1 yr)
-0.2
Missense Z
1.46
LOEUF
Clinical Summary— TMEM199
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
1 Pathogenic / Likely Pathogenic· 9 VUS of 18 total submissions
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 400 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/TMEM199?content-type=application/json&expand=1

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.
1.46LOEUF
pLI 0.000
Z-score 0.54
OE 0.81 (0.48–1.46)
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.
-0.25Z-score
OE missense 1.06 (0.92–1.23)
132 obs / 124.3 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.0.81 (0.48–1.46)
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 (0.92–1.23)
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.1.15
0≤1.21.6
LoF obs/exp: 8 / 9.8Missense obs/exp: 132 / 124.3Syn Z: -0.87
DN
0.6744th %ile
GOF
0.5465th %ile
LOF
0.3356th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

18 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS9
Benign8
1
Pathogenic
9
VUS
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
0
7
2
0
9
Likely Benign
0
0
0
0
0
Benign
1
0
6
1
8
Total179118

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM199 · protein map & ClinVar variants

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

Gene2Phenotype Curations

VMA12-related congenital disorder of glycosylation

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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