CENPJ

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: 12843329; 15793586; 16900296; 20522431; 20978018; 21668957; 22775483

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CENPJ variants in ClinVar

7 Conditions Cataloged

not providedTotal: 28

Seckel syndrome 4Total: 8

Microcephaly 6, primary, autosomal recessiveTotal: 5

Primary microcephaly;Intellectual disability, moderate;Perisylvian polymicrogyria;Lissencephaly type 3Total: 1

Microcephaly 1, primary, autosomal recessiveTotal: 1

Perisylvian polymicrogyria;Intellectual disability, moderate;Lissencephaly type 3;Primary microcephalyTotal: 1

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript . 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			10 clinvar	93 clinvar	5 clinvar	108
missense		2 clinvar	224 clinvar	14 clinvar	5 clinvar	245
nonsense	10 clinvar	9 clinvar	4 clinvar			23
start loss						0
frameshift	25 clinvar	7 clinvar	1 clinvar			33
splice donor/acceptor (+/-2bp)	1 clinvar	4 clinvar	2 clinvar			7
Total	36	22	241	107	10	416

Highest pathogenic variant AF is 0.0000788892

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 0 of 0 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
No transcripts match your selected source or search query.

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
Generic Transcription Pathway
Prolactin
RNA Polymerase II Transcription
Regulation of PLK1 Activity at G2/M Transition

Biological Process

G2/M transition of mitotic cell cycle
microtubule nucleation
centriole replication
smoothened signaling pathway
regulation of G2/M transition of mitotic cell cycle

Molecular Function

transcription corepressor activity
protein binding
tubulin binding
protein kinase binding
protein domain specific binding

Cellular Component

nucleus
nucleoplasm
centrosome
centriole
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381884
Coding exons: 16
Length: 39848
Individuals with no LoFs: 125632
Homozygous LoFs: 0
Heterozygous LoFs: 116
Defined: 125748
p: 0.000461

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.216	683	699	0.977	0.0000381	8908
Missense (PolyPhen)		144	155.65	0.92517		2051
Synonymous	0.521	241	252	0.958	0.0000140	2391
Loss of Function	1.74	50	65.1	0.768	0.00000361	795

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00081	0.00081	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00054	0.00054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00048	0.00047	rare
South Asian	0.00046	0.00039	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in cell division and centrosome function by participating in centriole duplication (PubMed:17681131, PubMed:20531387). Inhibits microtubule nucleation from the centrosome. Involved in the regulation of slow processive growth of centriolar microtubules. Acts as microtubule plus-end tracking protein that stabilizes centriolar microtubules and inhibits microtubule polymerization and extension from the distal ends of centrioles (PubMed:15047868, PubMed:27219064, PubMed:27306797). Required for centriole elongation and for STIL- mediated centriole amplification (PubMed:22020124). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865). May be involved in the control of centriolar-microtubule growth by acting as a regulator of tubulin release (PubMed:27306797). {ECO:0000269|PubMed:15047868, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:20531387, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27185865, ECO:0000269|PubMed:27219064, ECO:0000305|PubMed:27306797}.;
Disease: DISEASE: Microcephaly 6, primary, autosomal recessive (MCPH6) [MIM:608393]: A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. {ECO:0000269|PubMed:15793586, ECO:0000269|PubMed:22020124}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Seckel syndrome 4 (SCKL4) [MIM:613676]: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation. {ECO:0000269|PubMed:20522431}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.967
RVIS EVS: 0.83
RVIS percentile EVS: 88.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.117

Gene Damage Prediction

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