TRIP11

Chr 14AR

thyroid hormone receptor interactor 11

Also known as: ACG1A, CEV14, GMAP-210, GMAP210, ODCD, ODCD1, TRIP-11, TRIP230

NCBI Gene: 9321 ENSG00000100815 UniProt: Q15643 OMIM: 604505

The protein functions as a membrane tether essential for maintaining Golgi structure and efficient trafficking in the early secretory pathway between the endoplasmic reticulum and Golgi complex. Mutations cause achondrogenesis type IA and odontochondrodysplasia 1, severe skeletal disorders that primarily affect cartilage and bone development. The gene follows autosomal recessive inheritance and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene was identified based on the interaction of its protein product with thyroid hormone receptor beta. This protein is associated with the Golgi apparatus. The N-terminal region of the protein binds Golgi membranes and the C-terminal region binds the minus ends of microtubules; thus, the protein is thought to play a role in assembly and maintenance of the Golgi ribbon structure around the centrosome. Mutations in this gene cause achondrogenesis type IA.[provided by RefSeq, Mar 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Achondrogenesis, type IAMIM #200600

Odontochondrodysplasia 1MIM #184260

UniProtAchondrogenesis 1A

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · TRIP11-related skeletal dysplasia · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.000

Z-score 5.72

OE 0.39 (0.30–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.52Z-score

OE missense 0.95 (0.90–1.01)

903 obs / 947.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.30–0.50)

0≤0.351.4

Missense OE?0.95 (0.90–1.01)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 39 / 101.1Missense obs/exp: 903 / 947.7Syn Z: -0.89

Background carrier burden — how many people carry a rare variant somewhere in TRIP11?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 26

2,207 rare PASS variants

Rare truncating (LoF)

1 in 350

353 rare PASS variants

Rare synonymous (reference)

1 in 56

815 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRIP11. 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 37	1 in 340
South Asian	~43k	1 in 24	1 in 240
Remaining (unassigned)	~30k	1 in 25	1 in 330
European (Finnish)	~27k	1 in 84	1 in 2,400
Admixed American	~22k	1 in 27	1 in 970
African / African American	~21k	1 in 25	1 in 430
East Asian	~20k	1 in 26	1 in 470
Ashkenazi Jewish	~13k	1 in 89	1 in 1,000
Middle Eastern	~2,884	1 in 27	1 in 480

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 21 coding exons well covered in gnomAD exomes and genomes.? see exons ↓