TMEM184A

Chr 7

transmembrane protein 184A

Also known as: SDMG1, SLC51C1

NCBI Gene: 202915 ENSG00000164855 UniProt: Q6ZMB5

The TMEM184A protein acts as a heparin receptor in vascular cells and functions as a transmembrane transporter involved in vesicle transport, particularly in exocrine and Sertoli cells. Mutations in this gene cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delay. This gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

Predicted to enable heparin binding activity and transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to act upstream of or within germ-line sex determination; regulation of protein localization; and regulation of secretion. Predicted to be located in cytoplasmic vesicle; perinuclear region of cytoplasm; and plasma membrane. Predicted to be active in early endosome membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.37

Clinical Summary— TMEM184A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.37LOEUF

pLI 0.000

Z-score 0.34

OE 0.91 (0.62–1.37)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.50Z-score

OE missense 1.09 (0.99–1.20)

296 obs / 272.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.91 (0.62–1.37)

0≤0.351.4

Missense OE?1.09 (0.99–1.20)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 17 / 18.6Missense obs/exp: 296 / 272.6Syn Z: -2.23

This gene — mechanism propensity

0.7034th %ile

GOF

0.72top 25%

LOF

0.3941th %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.