TRAPPC2

Chr XXLR

trafficking protein particle complex subunit 2

Also known as: MIP2A, SEDL, SEDT, TRAPPC2P1, TRS20, ZNF547L, hYP38334

NCBI Gene: 6399 ENSG00000196459 UniProt: P0DI81 OMIM: 300202

The protein encoded by TRAPPC2 is part of a multi-subunit complex that targets and fuses endoplasmic reticulum-to-Golgi transport vesicles with their acceptor compartment, and can also bind c-myc promoter-binding protein 1 to block its transcriptional repression. Mutations cause spondyloepiphyseal dysplasia tarda, a skeletal dysplasia primarily affecting the spine and epiphyses that follows X-linked recessive inheritance. This gene is not highly constrained against loss-of-function variation, consistent with its X-linked inheritance pattern where hemizygous males would be affected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is thought to be part of a large multi-subunit complex involved in the targeting and fusion of endoplasmic reticulum-to-Golgi transport vesicles with their acceptor compartment. In addition, the encoded protein can bind c-myc promoter-binding protein 1 and block its transcriptional repression capability. Mutations in this gene are a cause of spondyloepiphyseal dysplasia tarda (SEDT). A processed pseudogene of this gene is located on chromosome 19, and other pseudogenes are found on chromosomes 8 and Y. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spondyloepiphyseal dysplasia tardaMIM #313400

XLR

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Spondyloepiphyseal dysplasia tarda; no ClinGen or GenCC tier

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

1.75

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — TRAPPC2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.75LOEUF

pLI 0.002

Z-score 0.27

OE 0.86 (0.42–1.75)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.53Z-score

OE missense 0.43 (0.31–0.60)

24 obs / 56.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.86 (0.42–1.75)

0≤0.351.4

Missense OE?0.43 (0.31–0.60)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 4 / 4.6Missense obs/exp: 24 / 56.4Syn Z: -0.43

Background carrier burden — how many people carry a rare variant somewhere in TRAPPC2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,600

88 rare PASS variants

Rare truncating (LoF)

1 in 1,200

16 rare PASS variants

Rare synonymous (reference)

1 in 810

50 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TRAPPC2; 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 · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 2,000	1 in 890
South Asian	~36k	1 in 980	≈ 1 in 8,000
Remaining (unassigned)	~31k	1 in 1,900	1 in 1,100
European (Finnish)	~27k	≈ 1 in 14,000	none seen
Admixed American	~23k	1 in 870	1 in 2,300
African / African American	~21k	1 in 1,000	≈ 1 in 4,300
East Asian	~20k	1 in 1,600	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 3,100	1 in 970

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