CACYBP

Chr 1

calcyclin binding protein

Also known as: GIG5, PNAS-107, S100A6BP, SIP

NCBI Gene: 27101 ENSG00000116161 UniProt: Q9HB71 OMIM: 606186

The protein serves as a molecular bridge in ubiquitin E3 complexes and participates in calcium-dependent ubiquitination and proteasomal degradation of target proteins, including beta-catenin. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures, developmental delay, and dystonia. The gene is highly constrained against loss-of-function variants, indicating that functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a calcyclin binding protein. It may be involved in calcium-dependent ubiquitination and subsequent proteosomal degradation of target proteins. It probably serves as a molecular bridge in ubiquitin E3 complexes and participates in the ubiquitin-mediated degradation of beta-catenin. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.38

Clinical Summary— CACYBP

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

19 VUS of 31 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.920

Z-score 3.01

OE 0.08 (0.03–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.14Z-score

OE missense 0.70 (0.59–0.84)

81 obs / 115.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.38)

0≤0.351.4

Missense OE?0.70 (0.59–0.84)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 12.5Missense obs/exp: 81 / 115.4Syn Z: -0.24

ClinVar Variant Classifications

31 submitted variants in ClinVar

ClinVar

Classification Summary

VUS19

Benign2

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	19	0	0	19
Likely Benign	0	0	0	0
Benign	0	1	1	2
Total	19	1	1	21

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap CACYBP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →