TRAPPC14

Chr 7AR

trafficking protein particle complex subunit 14

Also known as: C7orf43, MAP11, MCPH25

NCBI Gene: 55262 ENSG00000146826 UniProt: Q8WVR3 OMIM: 618350

The protein is a specific subunit of the TRAPP II complex that functions in Golgi trafficking and mediates vesicle transport to the mother centriole during ciliogenesis. Mutations cause primary autosomal recessive microcephaly 25, with autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.494), and the condition affects brain development with primary microcephaly present at birth.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables alpha-tubulin binding activity. Involved in cilium assembly and regulation of cell population proliferation. Located in centriolar satellite; midbody; and mitotic spindle. Part of TRAPPII protein complex. Implicated in primary autosomal recessive microcephaly 25. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Microcephaly 25, primary, autosomal recessiveMIM #618351

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.49

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.181

Z-score 3.40

OE 0.25 (0.14–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.21Z-score

OE missense 0.65 (0.58–0.73)

205 obs / 315.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.25 (0.14–0.49)

0≤0.351.4

Missense OE?0.65 (0.58–0.73)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 6 / 24.0Missense obs/exp: 205 / 315.8Syn Z: -1.09

Background carrier burden — how many people carry a rare variant somewhere in TRAPPC14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

657 rare PASS variants

Rare truncating (LoF)

1 in 4,400

74 rare PASS variants

Rare synonymous (reference)

1 in 130

396 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRAPPC14. 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 130	1 in 4,200
South Asian	~43k	1 in 84	1 in 4,100
Remaining (unassigned)	~30k	1 in 140	≈ 1 in 9,700
European (Finnish)	~27k	1 in 200	1 in 2,000
Admixed American	~22k	1 in 130	1 in 1,700
African / African American	~21k	1 in 130	1 in 3,100
East Asian	~20k	1 in 120	1 in 3,700
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 150	≈ 1 in 2,800

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): 10 of 11 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 11.? see exons ↓