TMEM161B

Chr 5

transmembrane protein 161B

TMEM161B encodes a plasma membrane protein that inhibits potassium and calcium currents in cardiomyocytes to maintain normal cardiac rhythm during heart development and ensure neonatal survival. Mutations cause autosomal recessive cardiac arrhythmias and sudden death in infancy. The gene shows tolerance to loss-of-function variants in the general population.

ResearchSummary from RefSeq, UniProt

Essential for maintaining normal cardiac rhythm in the developing heart and for neonatal survival (By similarity). Inhibits potassium and calcium currents in the cardiomyocytes, this assists in timely action potential repolarization and thereby maintains normal cardiac rhythm (By similarity)

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.72

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.000

Z-score 2.71

OE 0.45 (0.29–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.19Z-score

OE missense 0.78 (0.70–0.89)

191 obs / 243.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.29–0.72)

0≤0.351.4

Missense OE?0.78 (0.70–0.89)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 13 / 28.7Missense obs/exp: 191 / 243.3Syn Z: 0.14

Background carrier burden — how many people carry a rare variant somewhere in TMEM161B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

573 rare PASS variants

Rare truncating (LoF)

1 in 1,600

102 rare PASS variants

Rare synonymous (reference)

1 in 320

203 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM161B. 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 210	1 in 860
South Asian	~43k	1 in 120	1 in 3,100
Remaining (unassigned)	~30k	1 in 140	1 in 5,000
European (Finnish)	~27k	1 in 980	1 in 600
Admixed American	~22k	1 in 130	1 in 1,100
African / African American	~21k	1 in 160	1 in 1,500
East Asian	~20k	1 in 120	1 in 670
Ashkenazi Jewish	~13k	1 in 380	1 in 1,700
Middle Eastern	~2,884	1 in 150	≈ 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): 8 of 12 coding exons well covered in gnomAD exomes; exons 4, 5, 7, 9 marginal. Genomes: 11 of 12 (exon 5 below).? see exons ↓