TMEM8B

Chr 9

transmembrane protein 8B

Also known as: C9orf127, FP588, LINC00950, NAG-5, NAG5, NGX6, NGX6a

TMEM8B encodes a protein that regulates cell-matrix adhesion and may function as a regulator of the EGFR pathway involved in cell growth and proliferation. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.95), suggesting that mutations would likely cause severe developmental disorders. However, no specific disease phenotypes have been definitively associated with TMEM8B mutations in current databases.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.95
Clinical SummaryTMEM8B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.000
Z-score 1.73
OE 0.59 (0.380.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.91Z-score
OE missense 0.69 (0.620.78)
210 obs / 303.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.380.95)
00.351.4
Missense OE0.69 (0.620.78)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 12 / 20.5Missense obs/exp: 210 / 303.5Syn Z: 0.11
DN
0.6743th %ile
GOF
0.6638th %ile
LOF
0.3261th %ile

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

DNprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TMEM8B · 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.

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Clinical Literature
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