CCDC88B

Chr 11

coiled-coil and HOOK domain protein 88B

Also known as: BRLZ, CCDC88, HKRP3, gipie

NCBI Gene: 283234 ENSG00000168071 UniProt: A6NC98

This gene encodes a hook-related protein that regulates T-cell maturation and inflammatory function, enhances NK cell cytotoxicity through microtubule organization, and suppresses endoplasmic reticulum stress-induced apoptosis. Mutations cause autosomal recessive primary immunodeficiency with developmental delay and variable neurological features including intellectual disability and seizures. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the hook-related protein family. Members of this family are characterized by an N-terminal potential microtubule binding domain, a central coiled-coiled and a C-terminal Hook-related domain. The encoded protein may be involved in linking organelles to microtubules. [provided by RefSeq, Oct 2009]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.53

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.53LOEUF

pLI 0.000

Z-score 4.92

OE 0.39 (0.29–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.94Z-score

OE missense 0.91 (0.86–0.96)

777 obs / 854.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.29–0.53)

0≤0.351.4

Missense OE?0.91 (0.86–0.96)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 29 / 74.9Missense obs/exp: 777 / 854.6Syn Z: 1.38

Background carrier burden — how many people carry a rare variant somewhere in CCDC88B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 22

2,193 rare PASS variants

Rare truncating (LoF)

1 in 360

347 rare PASS variants

Rare synonymous (reference)

1 in 52

865 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCDC88B. 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 31	1 in 380
South Asian	~43k	1 in 21	1 in 360
Remaining (unassigned)	~30k	1 in 20	1 in 330
European (Finnish)	~27k	1 in 87	1 in 750
Admixed American	~22k	1 in 20	1 in 340
African / African American	~21k	1 in 17	1 in 240
East Asian	~20k	1 in 21	1 in 180
Ashkenazi Jewish	~13k	1 in 98	1 in 670
Middle Eastern	~2,884	1 in 19	1 in 310

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.

Exome coverage (gnomAD): 24 of 27 coding exons well covered in gnomAD exomes; exons 1, 17, 24 marginal. Genomes: all 27.? see exons ↓