CENPH

protein-coding

centromere protein H, the group of Constitutive centromere associated network

Gene summary

Centromere and kinetochore proteins play a critical role in centromere structure, kinetochore formation, and sister chromatid separation. The protein encoded by this gene colocalizes with inner kinetochore plate proteins CENP-A and CENP-C in both interphase and metaphase. It localizes outside of centromeric heterochromatin, where CENP-B is localized, and inside the kinetochore corona, where CENP-E is localized during prometaphase. It is thought that this protein can bind to itself, as well as to CENP-A, CENP-B or CENP-C. Multimers of the protein localize constitutively to the inner kinetochore plate and play an important role in the organization and function of the active centromere-kinetochore complex. [provided by RefSeq, Jul 2008]

MANE transcript

NM_022909.4

Inheritance

—

ClinVar variants

U:40B:3

Top phenotype

Recurrent spontaneous abortion

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr5:69,189,574-69,210,357

External References & Databases

Ensembl (ENSG00000153044)

Transcript & Mutation Effects

hg38 • Region Span ~20.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CENPH variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 37

Recurrent spontaneous abortionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022909.4. 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			1 clinvar			1
missense			38 clinvar	3 clinvar		41
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	40	3	0	43

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022909.4	RefSeq	NP_075060.1	9	MANE Select
ENST00000283006.7	Ensembl	ENSP00000283006.2	9	MANE Select
ENST00000502689.1	Ensembl	ENSP00000423936.1	8	Standard
ENST00000515001.5	Ensembl	ENSP00000426014.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cenph	Danio rerio	Structure: trunk Quality: curved dorsal abnormal

Gene / Model

Organism

Observed Phenotype

cenph

Danio rerio

Structure: trunk

Quality: curved dorsal

abnormal

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

CENP-A containing nucleosome assembly
kinetochore assembly
kinetochore organization

Molecular Function

protein binding
kinetochore binding

Cellular Component

kinetochore
condensed chromosome kinetochore
nucleus
nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000283006
Coding exons: 9
Length: 20810
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125744
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.645	96	116	0.831	0.00000517	1635
Missense (PolyPhen)		22	24.382	0.90229		427
Synonymous	-0.260	41	38.9	1.05	0.00000178	399
Loss of Function	1.12	13	18.1	0.716	0.00000106	206

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.000096	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00021	0.00020	rare
South Asian	0.00015	0.00013	rare
Other	0.00018	0.00016	rare

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. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate. {ECO:0000269|PubMed:14536089, ECO:0000269|PubMed:16875666, ECO:0000269|PubMed:18007590}.;

Recessive Scores

pRec: 0.0931

Intolerance Scores

LoFtool: 0.561
RVIS EVS: 0.01
RVIS percentile EVS: 54.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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