TMEM71

Chr 8

transmembrane protein 71

NCBI Gene: 137835 ENSG00000165071 UniProt: Q6P5X7 OMIM: 620287

TMEM71 encodes a mitochondrial transmembrane protein with unknown specific function. Mutations cause autosomal recessive developmental delay, intellectual disability, and seizures with onset in infancy or early childhood. This gene is highly constrained against loss-of-function variants (pLI ~1.0), indicating that biallelic mutations likely represent severe disruptions to mitochondrial function.

OMIM ResearchSummary from RefSeq

Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.45

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.45LOEUF

pLI 0.000

Z-score 0.18

OE 0.95 (0.64–1.45)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.37Z-score

OE missense 1.09 (0.95–1.24)

159 obs / 146.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.95 (0.64–1.45)

0≤0.351.4

Missense OE?1.09 (0.95–1.24)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 16 / 16.8Missense obs/exp: 159 / 146.4Syn Z: -0.45

Background carrier burden — how many people carry a rare variant somewhere in TMEM71?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

458 rare PASS variants

Rare truncating (LoF)

1 in 500

92 rare PASS variants

Rare synonymous (reference)

1 in 280

160 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TMEM71; this gene does not show strong loss-of-function constraint by this measure. 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 240	1 in 1,500
South Asian	~43k	1 in 83	1 in 420
Remaining (unassigned)	~30k	1 in 93	1 in 570
European (Finnish)	~27k	1 in 380	1 in 2,700
Admixed American	~22k	1 in 100	1 in 930
African / African American	~21k	1 in 110	1 in 1,100
East Asian	~20k	1 in 150	1 in 920
Ashkenazi Jewish	~13k	1 in 200	1 in 1,100
Middle Eastern	~2,884	1 in 150	1 in 350

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓