MPHOSPH8

protein-coding

M-phase phosphoprotein 8, the group of Ankyrin repeat domain containing

Gene summary

Enables chromatin binding activity and histone H3K9me2/3 reader activity. Involved in negative regulation of gene expression via chromosomal CpG island methylation; negative regulation of type I interferon production; and transposable element silencing by heterochromatin formation. Located in cytoplasm; heterochromatin; and nucleoplasm. Part of HUSH complex; HUSH2 complex; and nucleosome. Is active in chromatin and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_017520.4

Inheritance

—

ClinVar variants

U:88B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr13:19,633,659-19,673,441

External References & Databases

Ensembl (ENSG00000196199)

Transcript & Mutation Effects

hg38 • Region Span ~39.8 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 MPHOSPH8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 91

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017520.4. 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 clinvar		2
missense			84 clinvar	9 clinvar		93
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	88	10	0	98

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017520.4	RefSeq	NP_059990.2	14	MANE Select
ENST00000361479.10	Ensembl	ENSP00000355388.4	14	MANE Select
ENST00000414242.3	Ensembl	ENSP00000414663.3	3	Standard
ENST00000449056.1	Ensembl	ENSP00000405941.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of DNA methylation
negative regulation of transcription, DNA-templated

Molecular Function

protein binding
methylated histone binding

Cellular Component

nuclear nucleosome
nucleus
nuclear heterochromatin
nucleolus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361479
Coding exons: 14
Length: 39812
Individuals with no LoFs: 125696
Homozygous LoFs: 0
Heterozygous LoFs: 52
Defined: 125748
p: 0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	377	441	0.855	0.0000228	5693
Missense (PolyPhen)		113	163.13	0.6927		2078
Synonymous	-0.843	190	176	1.08	0.0000107	1553
Loss of Function	3.81	12	37.0	0.324	0.00000191	520

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00028	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.00027	0.00026	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Heterochromatin component that specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression (PubMed:20871592, PubMed:26022416). Mediates recruitment of the HUSH complex to H3K9me3 sites: the HUSH complex is recruited to genomic loci rich in H3K9me3 and is probably required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3 (PubMed:26022416). Binds H3K9me and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene (PubMed:20871592). Mediates down-regulation of CDH1 expression (PubMed:20871592). {ECO:0000269|PubMed:20871592, ECO:0000269|PubMed:26022416}.;

Recessive Scores

pRec: 0.0917

Intolerance Scores

LoFtool: 0.738
RVIS EVS: -0.24
RVIS percentile EVS: 36.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.690

Gene Damage Prediction

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