PPM1H

protein-coding

protein phosphatase, Mg2+/Mn2+ dependent 1H, the group of Protein phosphatases, Mg2+/Mn2+ dependent

Gene summary

Enables identical protein binding activity and phosphoprotein phosphatase activity. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

ARHCL1

MANE transcript

NM_020700.2

Inheritance

—

ClinVar variants

U:67B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr12:62,643,994-62,935,150

External References & Databases

Ensembl (ENSG00000111110)

Transcript & Mutation Effects

hg38 • Region Span ~291.2 kb

Loading mutation effect viewer...

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 PPM1H variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020700.2. 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						0
missense			66 clinvar		1 clinvar	67
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	67	0	1	68

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020700.2	RefSeq	NP_065751.1	10	MANE Select
ENST00000228705.7	Ensembl	ENSP00000228705.5	10	MANE Select
ENST00000938249.1	Ensembl	ENSP00000608308.1	10	Standard
ENST00001085162.1	Ensembl	ENSP00000754968.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein dephosphorylation

Molecular Function

phosphoprotein phosphatase activity
protein serine/threonine phosphatase activity
magnesium-dependent protein serine/threonine phosphatase activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000228705
Coding exons: 10
Length: 291056
Individuals with no LoFs: 124642
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 124650
p: 0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	223	296	0.753	0.0000169	3282
Missense (PolyPhen)		79	120.81	0.65389		1325
Synonymous	0.192	123	126	0.978	0.00000783	1063
Loss of Function	3.64	4	22.8	0.176	0.00000115	278

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000039	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Dephosphorylates CDKN1B at 'Thr-187', thus removing a signal for proteasomal degradation. {ECO:0000269|PubMed:22586611}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

RVIS EVS: 0.06
RVIS percentile EVS: 58.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.336

Gene Damage Prediction

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