TRANK1

Chr 3

tetratricopeptide repeat and ankyrin repeat containing 1

Also known as: LBA1

NCBI Gene: 9881 ENSG00000168016 UniProt: O15050 OMIM: 619316

The protein functions as a transcriptional regulator that controls gene expression in neural development and synaptic function. Mutations cause neurodevelopmental disorders with intellectual disability, autism spectrum disorder, and psychiatric features including bipolar disorder and schizophrenia, inherited in an autosomal dominant pattern. The gene shows moderate constraint against loss-of-function variants, and affected individuals typically present with early-onset developmental delays and behavioral abnormalities.

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.67

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.000

Z-score 4.48

OE 0.54 (0.43–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.08Z-score

OE missense 0.85 (0.81–0.89)

1329 obs / 1560.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.54 (0.43–0.67)

0≤0.351.4

Missense OE?0.85 (0.81–0.89)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 59 / 109.7Missense obs/exp: 1329 / 1560.7Syn Z: -0.35

Background carrier burden — how many people carry a rare variant somewhere in TRANK1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 19

3,557 rare PASS variants

Rare truncating (LoF)

1 in 310

411 rare PASS variants

Rare synonymous (reference)

1 in 25

1,493 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRANK1. 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 23	1 in 300
South Asian	~43k	1 in 18	1 in 340
Remaining (unassigned)	~30k	1 in 18	1 in 290
European (Finnish)	~27k	1 in 55	1 in 740
Admixed American	~22k	1 in 17	1 in 290
African / African American	~21k	1 in 18	1 in 540
East Asian	~20k	1 in 19	1 in 540
Ashkenazi Jewish	~13k	1 in 68	1 in 1,000
Middle Eastern	~2,884	1 in 20	≈ 1 in 580

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): 20 of 24 coding exons well covered in gnomAD exomes; exons 1, 2, 5, 6 marginal. Genomes: all 24.? see exons ↓