CCZ1

Chr 7

CCZ1 vacuolar protein trafficking and biogenesis associated

Also known as: C7orf28A, CCZ1A, CGI-43, H_DJ1163J12.2

NCBI Gene: 51622 ENSG00000122674 UniProt: P86791 OMIM: 620660

The protein acts as a guanine nucleotide exchange factor for RAB7 in concert with MON1A, promoting vesicle-mediated transport within cells. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene shows minimal constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in vacuolar transport and vesicle-mediated transport. Located in late endosome. Part of Mon1-Ccz1 complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.92

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.000

Z-score 1.83

OE 0.57 (0.36–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.19Z-score

OE missense 1.04 (0.93–1.17)

199 obs / 191.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.57 (0.36–0.92)

0≤0.351.4

Missense OE?1.04 (0.93–1.17)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 12 / 21.1Missense obs/exp: 199 / 191.5Syn Z: -0.87

Background carrier burden — how many people carry a rare variant somewhere in CCZ1?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

277 rare PASS variants

Rare truncating (LoF)

1 in 860

56 rare PASS variants

Rare synonymous (reference)

1 in 220

101 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCZ1. 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)	~555k	1 in 120	1 in 940
South Asian	~43k	1 in 130	1 in 1,700
Remaining (unassigned)	~30k	1 in 85	1 in 770
European (Finnish)	~27k	1 in 290	1 in 4,300
Admixed American	~22k	1 in 190	1 in 1,200
African / African American	~21k	1 in 110	1 in 870
East Asian	~20k	1 in 140	1 in 620
Ashkenazi Jewish	~13k	1 in 1,400	none seen
Middle Eastern	~2,872	1 in 120	none seen

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): 6 of 15 coding exons well covered in gnomAD exomes; exons 1, 4, 11, 13 poorly covered; exons 2, 7, 9, 10, 14 marginal. Genomes: 2 of 15 (exons 1, 2, 3, 4, 5 and 8 more below).? see exons ↓