TMEM184B

Chr 22

transmembrane protein 184B

Also known as: C22orf5, FM08, HS5O6A, HSPC256, SLC51C2

This gene encodes a predicted transmembrane transporter that may activate MAP kinase signaling pathways. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.514), but no definitive human disease associations have been established. Clinical significance of variants in TMEM184B remains uncertain pending further research.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.51
Clinical SummaryTMEM184B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.373
Z-score 3.03
OE 0.22 (0.110.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.06Z-score
OE missense 0.64 (0.560.73)
165 obs / 258.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.22 (0.110.51)
00.351.4
Missense OE0.64 (0.560.73)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 4 / 17.8Missense obs/exp: 165 / 258.3Syn Z: 0.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTMEM184B-related neurodevelopmental disorderLOFAD
DN
0.6744th %ile
GOF
0.77top 25%
LOF
0.3551th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TMEM184B · 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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