TMEM39A

Chr 3

transmembrane protein 39A

Also known as: SUSR2

NCBI Gene: 55254 ENSG00000176142 UniProt: Q9NV64 OMIM: 621550

Involved in negative regulation of autophagosome assembly; negative regulation of autophagosome maturation; and positive regulation of viral genome replication. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.34

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.955

Z-score 3.86

OE 0.13 (0.06–0.34)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.55Z-score

OE missense 0.73 (0.65–0.83)

198 obs / 269.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.06–0.34)

0≤0.351.4

Missense OE?0.73 (0.65–0.83)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 3 / 22.9Missense obs/exp: 198 / 269.5Syn Z: 0.71

Background carrier burden — how many people carry a rare variant somewhere in TMEM39A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

469 rare PASS variants

Rare truncating (LoF)

1 in 6,400

46 rare PASS variants

Rare synonymous (reference)

1 in 330

210 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM39A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 11,000
South Asian	~43k	1 in 220	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 140	≈ 1 in 7,500
European (Finnish)	~27k	1 in 760	1 in 3,800
Admixed American	~22k	1 in 150	1 in 2,000
African / African American	~21k	1 in 170	1 in 3,100
East Asian	~20k	1 in 200	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 1,900	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 210	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓