CCDC28B

protein-coding

coiled-coil domain containing 28B

Gene summary

The product of this gene localizes to centrosomes and basal bodies. The protein colocalizes with several proteins associated with Bardet-Biedl syndrome (BBS) and participates in the regulation of cilia development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

MANE transcript

NM_024296.5

Inheritance

AR, AD

ClinVar variants

U:43B:4

Top phenotype

Bardet-Biedl syndrome, modifier of

gnomAD constraint

pLI —, LoF o/e 1.46

Max pathogenic AF

—

Genomic locus

chr1:32,200,595-32,205,453

External References & Databases

Ensembl (ENSG00000160050)

Transcript & Mutation Effects

hg38 • Region Span ~4.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Bardet-Biedl syndrome 1NO_KNOWN

Inheritance Pattern: AR

Disease ID:MONDO:0008854

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Bardet-Biedl syndrome, modifier ofAD

Manifestation: General

Intervention: General

Rationale: Variants are described as related to modifying alleles, with little evidence that the variant would cause disease alone

Refs: 12677556; 16327777; 22773737

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCDC28B variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 36

not providedTotal: 6

Bardet-Biedl syndrome 1Total: 2

CCDC28B-related disorderTotal: 2

Bardet-Biedl syndrome 1, modifier ofTotal: 1

Bardet-Biedl syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024296.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar		5
missense			36 clinvar	1 clinvar		37
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	43	4	0	47

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024296.5	RefSeq	NP_077272.2	5	MANE Select
ENST00000373602.10	Ensembl	ENSP00000362704.5	5	MANE Select
NM_001301011.2	RefSeq	NP_001287940.1	4	Standard
NM_001437632.1	RefSeq	NP_001424561.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ccdc28b	Danio rerio	Structure: cell Quality: detached from abnormal

Gene / Model

Organism

Observed Phenotype

ccdc28b

Danio rerio

Structure: cell

Quality: detached from

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cilium assembly

Molecular Function

protein binding

Cellular Component

cytoplasm
centrosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373602
Coding exons: 5
Length: 5002
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125740
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.03	83	114	0.729	0.00000668	1287
Missense (PolyPhen)		23	35.273	0.65205		418
Synonymous	0.133	48	49.2	0.976	0.00000294	403
Loss of Function	-1.18	11	7.51	1.46	3.17e-7	103

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00044	0.00040	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00015	rare
South Asian	0.00017	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in ciliogenesis. Regulates cilia length through its interaction with MAPKAP1/SIN1 but independently of mTORC2 complex. Modulates mTORC2 complex assembly and function, possibly enhances AKT1 phosphorylation. Does not seem to modulate assembly and function of mTORC1 complex. {ECO:0000269|PubMed:23015189, ECO:0000269|PubMed:23727834}.;
Disease: DISEASE: Bardet-Biedl syndrome (BBS) [MIM:209900]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:16327777}. Note=The gene represented in this entry acts as a disease modifier.;

Recessive Scores

pRec: 0.183

Intolerance Scores

LoFtool: 0.783
RVIS EVS: 0.26
RVIS percentile EVS: 70.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0312

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium