TMEM114

Chr 16

transmembrane protein 114

NCBI Gene: 283953 ENSG00000232258 UniProt: B3SHH9

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.

ResearchSummary from RefSeq

This gene encodes a glycosylated transmembrane protein that plays a role in lens and eye development. Mutations in this gene, including a t(16;22)(p13.3;q11.2) translocation, are associated with congenital and juvenile cataract disorders. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.82

Clinical Summary— TMEM114

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Population Constraint (gnomAD)

Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 total variants — no pathogenic classifications of 3 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.82LOEUF

pLI 0.033

Z-score 0.29

OE 0.80 (0.31–1.82)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.36Z-score

OE missense 1.12 (0.93–1.35)

81 obs / 72.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.80 (0.31–1.82)

0≤0.351.4

Missense OE?1.12 (0.93–1.35)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

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

This gene — mechanism propensity

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

3 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Benign2

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Synonymous	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	0	0
Likely Benign	2	2
Benign	0	0
Total	2	2

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap TMEM114 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →