CENPT

protein-coding

centromere protein T, the group of Constitutive centromere associated network

Gene summary

The centromere is a specialized chromatin domain, present throughout the cell cycle, that acts as a platform on which the transient assembly of the kinetochore occurs during mitosis. All active centromeres are characterized by the presence of long arrays of nucleosomes in which CENPA (MIM 117139) replaces histone H3 (see MIM 601128). CENPT is an additional factor required for centromere assembly (Foltz et al., 2006 [PubMed 16622419]).[supplied by OMIM, Mar 2008]

Previous symbols:

C16orf56

MANE transcript

NM_025082.4

Inheritance

ClinVar variants

P:1U:112B:25

Top phenotype

Short stature and microcephaly with genital anomalies

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr16:67,828,157-67,847,811

External References & Databases

Ensembl (ENSG00000102901)

Transcript & Mutation Effects

hg38 • Region Span ~19.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

short stature and microcephaly with genital anomaliesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032875

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Short stature and microcephaly with genital anomaliesAR

Manifestation: Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic

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: 29228025

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CENPT variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 146

not providedTotal: 141

THAP11-related disorderTotal: 20

CENPT-related disorderTotal: 16

Spinocerebellar ataxia 51Total: 1

Disorders of Intracellular Cobalamin MetabolismTotal: 1

Methylmalonic aciduria and homocystinuria, cb1L typeTotal: 1

Short stature and microcephaly with genital anomaliesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025082.4. 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				7 clinvar	1 clinvar	8
missense			104 clinvar	13 clinvar	4 clinvar	121
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		7 clinvar			8
Total	1	0	112	20	5	138

Highest pathogenic variant AF is 6.8429785e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025082.4	RefSeq	NP_079358.3	13	MANE Select
ENST00000562787.6	Ensembl	ENSP00000457810.1	13	MANE Select
ENST00000440851.6	Ensembl	ENSP00000400140.2	13	Standard
ENST00000440851.7	Ensembl	ENSP00000400140.2	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
Amplification of signal from the kinetochores
Mitotic Spindle Checkpoint
Cell Cycle Checkpoints

Biological Process

mitotic cell cycle
regulation of transcription by RNA polymerase II
chromosome segregation
CENP-A containing nucleosome assembly
chromosome organization

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
protein binding
protein heterodimerization activity

Cellular Component

chromosome, centromeric region
kinetochore
condensed chromosome kinetochore
nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000562787
Coding exons: 13
Length: 19655
Individuals with no LoFs: 124773
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 124808
p: 0.000140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.136	312	319	0.979	0.0000179	3549
Missense (PolyPhen)		84	83.931	1.0008		984
Synonymous	0.172	129	132	0.981	0.00000760	1215
Loss of Function	2.45	13	26.7	0.487	0.00000139	300

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00026	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00044	0.00042	rare
European (Non-Finnish)	0.00010	0.000097	rare
South Asian	0.00021	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Part of a nucleosome- associated complex that binds specifically to histone H3- containing nucleosomes at the centromere, as opposed to nucleosomes containing CENPA. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. CENPT has a fundamental role in kinetochore assembly and function. It is one of the inner kinetochore proteins, with most further proteins binding downstream. Required for normal chromosome organization and normal progress through mitosis. {ECO:0000269|PubMed:16716197, ECO:0000269|PubMed:21529714, ECO:0000269|PubMed:21695110}.;

Recessive Scores

pRec: 0.0660

Intolerance Scores

LoFtool: 0.592
RVIS EVS: 1.29
RVIS percentile EVS: 93.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Indispensability pred.: N
Indispensability score: 0.271

Gene Damage Prediction

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