GeneBe

CEP19

protein-coding

centrosomal protein 19

Gene summary

The protein encoded by this gene localizes to centrosomes and primary cilia and co-localizes with a marker for the mother centriole. This gene resides in a region of human chromosome 3 that is linked to morbid obesity. A homozygous knockout of the orthologous gene in mouse resulted in mice with morbid obesity, hyperphagy, glucose intolerance, and insulin resistance. Mutations in this gene cause morbid obesity and spermatogenic failure (MOSPGF). This gene has a pseudogene on human chromosome 2. [provided by RefSeq, Apr 2014]

Previous symbols:
  • C3orf34

MANE transcript

NM_032898.5

Inheritance

AR

ClinVar variants

P:3U:76B:30

Top phenotype

Morbid obesity and spermatogenic failure

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr3:196,706,277-196,712,250

External References & Databases

Ensembl (ENSG00000174007)NCBI Gene (84984)OMIM (615586)HGNC:28209GenCCUniProt (Q96LK0)AlphaFoldClinVar (CEP19)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~6.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

obesity due to CEP19 deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014309

Submitter: Ambry Genetics

obesity due to CEP19 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014309

Submitter: Labcorp Genetics (formerly Invitae)

obesity due to CEP19 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014309

Submitter: Genomics England PanelApp

obesity due to CEP19 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014309

Submitter: Orphanet

Bardet-Biedl syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015229

Submitter: Orphanet

Clinical Genomic Database (CGD)

Morbid obesity and spermatogenic failureAR

Manifestation: Endocrine; Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 24268657Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CEP19 variants in ClinVar

6 Conditions Cataloged
not providedTotal: 104
not specifiedTotal: 22
Obesity due to CEP19 deficiencyTotal: 3
CEP19-related disorderTotal: 2
Optic atrophyTotal: 1
Bardet-Biedl syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032898.5. 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.

EffectPLPVUSLBBSum
synonymous
27
clinvar
2
clinvar
 29
missense
65
clinvar
1
clinvar
 66
nonsense
1
clinvar
1
clinvar
4
clinvar
 6
start loss
1
clinvar
 1
frameshift
1
clinvar
5
clinvar
 6
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total2176273109

Highest pathogenic variant AF is 0.0000117718055

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_032898.5RefSeqNP_116287.32MANE Select
ENST00000409690.5EnsemblENSP00000387209.42MANE Select
NM_001379468.1RefSeqNP_001366397.12Standard
NM_001379469.1RefSeqNP_001366398.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • microtubule anchoring at centrosome
  • cilium assembly
  • vesicle targeting, trans-Golgi to periciliary membrane compartment

Molecular Function

  • protein binding

Cellular Component

  • spindle pole
  • centrosome
  • centriole
  • cilium
  • ciliary basal body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000409690
Coding exons
2
Length
6017
Individuals with no LoFs
124774
Homozygous LoFs
0
Heterozygous LoFs
18
Defined
124792
p
0.0000721
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.1369490.41.040.000004771116
Missense (PolyPhen)2825.8911.0815359
Synonymous0.08823030.60.9800.00000151287
Loss of Function1.4048.390.4776.03e-784

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.000370.00037rare
European (Non-Finnish)0.0000540.000053rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Required for ciliation (PubMed:28625565, PubMed:28428259, PubMed:28659385). Recruits the RABL2B GTPase to the ciliary base to initiate ciliation. After specifically capturing the activated GTP-bound RABL2B, the CEP19-RABL2B complex binds intraflagellar transport (IFT) complex B from the large pool pre-docked at the base of the cilium and thus triggers its entry into the cilia (PubMed:28625565, PubMed:28428259). Involved in the early steps in cilia formation by recruiting the ciliary vesicles (CVs) to the distal end of the mother centriole where they fuse to initiate cilium assembly. Involved in microtubule (MT) anchoring to the centrosomes (PubMed:28659385). {ECO:0000269|PubMed:28428259, ECO:0000269|PubMed:28625565, ECO:0000269|PubMed:28659385}.;
Disease
DISEASE: Morbid obesity and spermatogenic failure (MOSPGF) [MIM:615703]: An autosomal recessive morbid obesity syndrome characterized by hypertension, fatty liver disease, insulin resistance, and decreased sperm counts. Variable clinical manifestations are early coronary artery disease with myocardial infarction before 45 years of age, type II diabetes mellitus, and intellectual disability. Morbid obese individuals are defined as having a BMI greater than 40. {ECO:0000269|PubMed:24268657}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.0926

Intolerance Scores

RVIS EVS
0.01
RVIS percentile EVS
54.95

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.114

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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