TMEM200C

Chr 18

transmembrane protein 200C

Also known as: TTMA

TMEM200C encodes a protein predicted to be located in cellular membranes, though its specific function remains poorly characterized. Mutations in this gene have been associated with neurodevelopmental disorders, but the clinical phenotype and inheritance pattern are not well-established in the current literature. The gene shows relatively low constraint against loss-of-function variants, suggesting it may tolerate some degree of functional disruption.

Summary from RefSeq
Research Assistant →
0
Active trials
1
Pubs (1 yr)
117
P/LP submissions
P/LP missense
1.24
LOEUF
GOF
Mechanism· predicted
Clinical SummaryTMEM200C
Population Constraint (gnomAD)
Low constraint (pLI 0.11) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
112 unique Pathogenic / Likely Pathogenic· 7 VUS of 126 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.24LOEUF
pLI 0.106
Z-score 1.25
OE 0.40 (0.161.24)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.10Z-score
OE missense 1.02 (0.921.13)
263 obs / 258.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.40 (0.161.24)
00.351.4
Missense OE1.02 (0.921.13)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 2 / 5.0Missense obs/exp: 263 / 258.4Syn Z: -1.62
DN
0.5574th %ile
GOF
0.6638th %ile
LOF
0.60top 25%

The highest-scoring mechanism for this gene is gain-of-function.

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

126 submitted variants in ClinVar

Classification Summary

Pathogenic111
Likely Pathogenic1
VUS7
Likely Benign6
111
Pathogenic
1
Likely Pathogenic
7
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
111
Likely Pathogenic
1
VUS
7
Likely Benign
6
Benign
0
Total125

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TMEM200C · 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

No active trials found for this gene.

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Clinical Literature
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