TMEM184B

Chr 22

transmembrane protein 184B

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

NCBI Gene: 25829 ENSG00000198792 UniProt: Q9Y519 OMIM: 621411

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.51

Clinical Summary— TMEM184B

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

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ClinVar Variants

45 VUS of 67 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.373

Z-score 3.03

OE 0.22 (0.11–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.06Z-score

OE missense 0.64 (0.56–0.73)

165 obs / 258.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.22 (0.11–0.51)

0≤0.351.4

Missense OE?0.64 (0.56–0.73)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 4 / 17.8Missense obs/exp: 165 / 258.3Syn Z: 0.16

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedTMEM184B-related neurodevelopmental disorderLOFAD

This gene — mechanism propensity

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

67 submitted variants in ClinVar

ClinVar

Classification Summary

VUS45

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	44	45
Likely Benign	0	2	2
Benign	0	0	0
Total	1	46	47

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap TMEM184B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →