CENPJ

centromere protein J

Basic information

Region (hg38): 13:24882278-24922889

Previous symbols: [ "MCPH6" ]

Links

ENSG00000151849 ∙ NCBI:55835 ∙ OMIM:609279 ∙ HGNC:17272 ∙ Uniprot:Q9HC77 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Seckel syndrome 4 (Definitive), mode of inheritance: AR
• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
• Seckel syndrome (Supportive), mode of inheritance: AR
• microcephaly 6, primary, autosomal recessive (Strong), mode of inheritance: AR
• microcephaly 6 with or without short stature (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Seckel syndrome 4; Microcephaly, primary autosomal recessive, 6	AR	General	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	Craniofacial; Musculoskeletal; Neurologic	12843329; 15793586; 16900296; 20522431; 20978018; 21668957; 22775483

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CENPJ gene.

• not provided (397 variants)
• Microcephaly 6, primary, autosomal recessive (131 variants)
• Seckel syndrome 4 (118 variants)
• Inborn genetic diseases (62 variants)
• not specified (54 variants)
• Primary Microcephaly, Recessive (14 variants)
• Seckel syndrome (14 variants)
• Microcephaly 6, primary, autosomal recessive;Seckel syndrome 4 (9 variants)
• Seckel syndrome 4;Microcephaly 6, primary, autosomal recessive (7 variants)
• Microcephaly 1, primary, autosomal recessive (2 variants)
• Seckel syndrome 1 (2 variants)
• CENPJ-Related Disorders (1 variants)
• Autosomal recessive primary microcephaly (1 variants)
• Lissencephaly type 3;Intellectual disability, moderate;Perisylvian polymicrogyria;Primary microcephaly (1 variants)
• CENPJ-related condition (1 variants)
• Lissencephaly;Microcephaly (1 variants)
• Perisylvian polymicrogyria;Lissencephaly type 3;Primary microcephaly;Intellectual disability, moderate (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CENPJ gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			13	65	5	83
missense		2	182	8	5	197
nonsense	8	8	3			19
start loss						0
frameshift	22	6	1			29
inframe indel			8			8
splice donor/acceptor (+/-2bp)		3	2			5
splice region			9	3	2	14
non coding			26	50	46	122
Total	30	19	235	123	56

Highest pathogenic variant AF is 0.0000789

Variants in CENPJ

This is a list of pathogenic ClinVar variants found in the CENPJ region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-24882287-A-G		Seckel syndrome 4 • Microcephaly 6, primary, autosomal recessive	Conflicting classifications of pathogenicity (Jan 12, 2018)
13-24882394-G-A		Microcephaly 6, primary, autosomal recessive • Seckel syndrome 4	Uncertain significance (Jan 12, 2018)
13-24882398-T-A		Seckel syndrome 4 • Microcephaly 6, primary, autosomal recessive	Uncertain significance (Jan 13, 2018)
13-24882418-C-CAAGT		Primary Microcephaly, Recessive • Seckel syndrome	Uncertain significance (Jun 14, 2016)
13-24882456-C-T		Seckel syndrome 4 • Microcephaly 6, primary, autosomal recessive	Uncertain significance (Jan 13, 2018)
13-24882493-G-GT		Seckel syndrome • Primary Microcephaly, Recessive	Benign (May 10, 2021)
13-24882538-A-G		Seckel syndrome 4 • Microcephaly 6, primary, autosomal recessive	Benign (May 10, 2021)
13-24882554-T-C		Microcephaly 6, primary, autosomal recessive • Seckel syndrome 4	Benign/Likely benign (May 11, 2021)
13-24882581-C-CAT		Seckel syndrome • Primary Microcephaly, Recessive	Conflicting classifications of pathogenicity (May 01, 2023)
13-24882584-T-G		Seckel syndrome 4 • Microcephaly 6, primary, autosomal recessive	Uncertain significance (Jan 13, 2018)
13-24882607-A-G		Seckel syndrome 4 • Microcephaly 6, primary, autosomal recessive	Benign/Likely benign (Nov 01, 2022)
13-24882608-T-C		Seckel syndrome 4 • Microcephaly 6, primary, autosomal recessive	Uncertain significance (Jan 12, 2018)
13-24882621-T-G		Microcephaly 6, primary, autosomal recessive • Seckel syndrome 4	Conflicting classifications of pathogenicity (Jan 13, 2018)
13-24882636-A-G		Microcephaly 6, primary, autosomal recessive • Seckel syndrome 4	Uncertain significance (Jan 12, 2018)
13-24882657-T-C		Microcephaly 6, primary, autosomal recessive • Seckel syndrome 4	Uncertain significance (Jan 13, 2018)
13-24882713-T-C		Microcephaly 6, primary, autosomal recessive • Seckel syndrome 4	Uncertain significance (Jan 13, 2018)
13-24882769-CAG-C		Seckel syndrome • Primary Microcephaly, Recessive	Likely benign (Jun 14, 2016)
13-24882773-G-A		Seckel syndrome 4 • Microcephaly 6, primary, autosomal recessive	Benign (May 10, 2021)
13-24882779-T-C		Microcephaly 6, primary, autosomal recessive • Seckel syndrome 4	Benign (May 10, 2021)
13-24882861-C-T		Microcephaly 6, primary, autosomal recessive • Seckel syndrome 4	Uncertain significance (Jan 12, 2018)
13-24882866-ACTT-A		Primary Microcephaly, Recessive • Seckel syndrome	Benign (Jun 14, 2016)
13-24882874-G-T		Microcephaly 6, primary, autosomal recessive • Seckel syndrome 4	Uncertain significance (Jan 12, 2018)
13-24882874-GT-G		Seckel syndrome • Primary Microcephaly, Recessive	Benign (Jun 14, 2016)
13-24882885-T-A		Seckel syndrome 4 • Microcephaly 6, primary, autosomal recessive	Uncertain significance (Jan 13, 2018)
13-24882910-C-T		Microcephaly 6, primary, autosomal recessive • Seckel syndrome 4	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CENPJ	protein_coding	protein_coding	ENST00000381884	16	39848

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.06e-27	0.0627	125632	0	116	125748	0.000461

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.216	683	699	0.977	0.0000381	8908
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00130	0.00130
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000544	0.000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000476	0.000475
Middle Eastern	0.000544	0.000544
South Asian	0.000458	0.000392
Other	0.000163	0.000163

dbNSFP

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.
• Pathway: Gene expression (Transcription);Generic Transcription Pathway;Prolactin;RNA Polymerase II Transcription;Regulation of PLK1 Activity at G2/M Transition;TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain;TP53 Regulates Transcription of Cell Cycle Genes;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Transcriptional Regulation by TP53;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Intolerance Scores

• loftool: 0.967
• rvis_EVS: 0.83
• rvis_percentile_EVS: 88.13

Haploinsufficiency Scores

• pHI: 0.167
• hipred: N
• hipred_score: 0.438
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.117

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cenpj
• Phenotype: muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype

Gene ontology

• 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;motile cilium assembly;regulation of centriole replication;microtubule polymerization;cell division;centriole elongation;ciliary basal body-plasma membrane docking;positive regulation of non-motile cilium assembly;positive regulation of centriole elongation;positive regulation of establishment of protein localization;non-motile cilium assembly
• Cellular component: nucleus;nucleoplasm;centrosome;centriole;cytosol;microtubule;plasma membrane;gamma-tubulin small complex;ciliary basal body
• Molecular function: transcription corepressor activity;protein binding;tubulin binding;protein kinase binding;protein domain specific binding;identical protein binding