MIS18A

protein-coding

MIS18 kinetochore protein A

Gene summary

Enables identical protein binding activity. Predicted to be involved in CENP-A containing chromatin assembly. Predicted to act upstream of or within chromosome segregation; obsolete pericentric heterochromatin organization; and protein localization to chromosome, centromeric region. Predicted to be located in nucleoplasm. Predicted to be part of CENP-A recruiting complex. Predicted to be active in chromatin; chromosome, centromeric region; and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C21orf46
C21orf45

MANE transcript

NM_018944.3

Inheritance

—

ClinVar variants

U:31B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr21:32,268,228-32,279,049

External References & Databases

Ensembl (ENSG00000159055)

Transcript & Mutation Effects

hg38 • Region Span ~10.8 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 MIS18A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018944.3. 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					2 clinvar	2
missense			30 clinvar	3 clinvar		33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	31	3	2	36

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018944.3	RefSeq	NP_061817.1	5	MANE Select
ENST00000290130.4	Ensembl	ENSP00000290130.3	5	MANE Select
ENST00000926599.1	Ensembl	ENSP00000596658.1	5	Standard
ENST00000956396.1	Ensembl	ENSP00000626455.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Nucleosome assembly
Chromosome Maintenance
Deposition of new CENPA-containing nucleosomes at the centromere
Cell Cycle

Biological Process

cell cycle
chromosome segregation
CENP-A containing nucleosome assembly
regulation of DNA methylation
cell division

Molecular Function

protein binding
metal ion binding

Cellular Component

chromosome, centromeric region
chromatin
nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000290130
Coding exons: 5
Length: 10851
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125747
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.124	130	126	1.03	0.00000617	1510
Missense (PolyPhen)		25	37.888	0.65984		483
Synonymous	-0.382	56	52.5	1.07	0.00000267	424
Loss of Function	1.59	5	10.6	0.473	4.47e-7	137

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis. {ECO:0000269|PubMed:17199038}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

RVIS EVS: -0.1
RVIS percentile EVS: 46.49

Essentials

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

Gene Damage Prediction

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