This gene encodes a glycosylated transmembrane protein involved in lens and eye development. Mutations cause congenital and juvenile cataract disorders with autosomal dominant inheritance. The gene shows low constraint to loss-of-function variation, suggesting tolerance to such variants in the general population.

OMIMResearchSummary from RefSeq
LOFmechanismLOEUF 1.82
Clinical SummaryTMEM114
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 13 VUS of 37 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.82LOEUF
pLI 0.033
Z-score 0.29
OE 0.80 (0.311.82)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.36Z-score
OE missense 1.12 (0.931.35)
81 obs / 72.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.80 (0.311.82)
00.351.4
Missense OE1.12 (0.931.35)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 2 / 2.5Missense obs/exp: 81 / 72.4Syn Z: -0.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTMEM114-related congenital and juvenile cataractLOFAD
DN
0.6454th %ile
GOF
0.75top 25%
LOF
0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

37 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS13
Likely Benign2
20
Pathogenic
1
Likely Pathogenic
13
VUS
2
Likely Benign

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
Likely Pathogenic
1
VUS
13
Likely Benign
2
Benign
0
Total36

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TMEM114 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗