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 vesicle-mediated transport. Located in intracellular membrane-bounded organelle. Part of Mon1-Ccz1 complex. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.92

Clinical Summary— CCZ1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 92 VUS of 129 total submissions

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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

ClinVar Variant Classifications

129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS92

Likely Benign4

Benign2

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	2
Likely Pathogenic	0	0	0	0
VUS	92	0	0	92
Likely Benign	3	0	1	4
Benign	1	1	0	2
Total	96	3	1	100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

45 pathogenic / likely-pathogenic (of 66) ClinVar copy-number / structural variants overlap CCZ1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →