TUBGCP6

Chr 22AR

tubulin gamma complex component 6

Also known as: GCP-6, GCP6, MCCRP, MCCRP1, MCPHCR

NCBI Gene: 85378 ENSG00000128159 UniProt: Q96RT7 OMIM: 610053

TUBGCP6 encodes a component of the gamma-tubulin ring complex (gTuRC) that mediates microtubule nucleation at the centrosome, which is critical for centrosome duplication and spindle formation. Biallelic mutations cause microcephaly and chorioretinopathy, autosomal recessive, 1, affecting both brain development and retinal structure. This follows autosomal recessive inheritance and has an associated GeneReviews entry for additional clinical guidance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is part of a large multisubunit complex required for microtubule nucleation at the centrosome. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Microcephaly and chorioretinopathy, autosomal recessive, 1MIM #251270

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · microcephaly and chorioretinopathy 1 · AR · ClinGen 2023

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

0.93

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — TUBGCP6

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?

0.93LOEUF

pLI 0.000

Z-score 2.10

OE 0.74 (0.60–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.94Z-score

OE missense 1.08 (1.03–1.13)

1215 obs / 1125.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.74 (0.60–0.93)

0≤0.351.4

Missense OE?1.08 (1.03–1.13)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 59 / 79.2Missense obs/exp: 1215 / 1125.8Syn Z: -4.14

Background carrier burden — how many people carry a rare variant somewhere in TUBGCP6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 16

2,878 rare PASS variants

Rare truncating (LoF)

1 in 300

450 rare PASS variants

Rare synonymous (reference)

1 in 31

1,118 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TUBGCP6. 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 22	1 in 360
South Asian	~43k	1 in 15	1 in 320
Remaining (unassigned)	~30k	1 in 13	1 in 280
European (Finnish)	~27k	1 in 46	1 in 320
Admixed American	~22k	1 in 15	1 in 260
African / African American	~21k	1 in 15	1 in 330
East Asian	~20k	1 in 18	1 in 190
Ashkenazi Jewish	~13k	1 in 76	1 in 900
Middle Eastern	~2,884	1 in 16	1 in 470

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.