TMEM225

protein-coding

transmembrane protein 225, the group of Protein phosphatase 1 regulatory subunits

Gene summary

Predicted to enable protein phosphatase 1 binding activity and protein phosphatase inhibitor activity. Predicted to be involved in negative regulation of phosphatase activity. Predicted to be located in inner acrosomal membrane and outer acrosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001013743.3

Inheritance

—

ClinVar variants

U:29B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr11:123,882,920-123,885,670

External References & Databases

Ensembl (ENSG00000204300)

Transcript & Mutation Effects

hg38 • Region Span ~2.8 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 TMEM225 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001013743.3. 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						0
missense			29 clinvar	5 clinvar		34
nonsense						0
start loss				1 clinvar		1
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	29	6	0	35

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001013743.3	RefSeq	NP_001013765.2	4	MANE Select
ENST00000375026.7	Ensembl	ENSP00000364166.2	4	MANE Select
NM_001363605.2	RefSeq	NP_001350534.1	4	Standard
ENST00000528595.1	Ensembl	ENSP00000431282.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of phosphatase activity

Cellular Component

acrosomal membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375026
Coding exons: 4
Length: 2717
Individuals with no LoFs: 125242
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125244
p: 0.00000798

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.337	111	121	0.914	0.00000602	1492
Missense (PolyPhen)		20	24.729	0.80877		333
Synonymous	-0.950	53	44.9	1.18	0.00000245	414
Loss of Function	0.798	5	7.33	0.682	3.11e-7	89

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000090	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably inhibits protein phosphatase 1 (PP1) in sperm via binding to catalytic subunit PPP1CC. {ECO:0000250|UniProtKB:Q9D9S2}.;

Intolerance Scores

LoFtool: 0.501
RVIS EVS: 1.02
RVIS percentile EVS: 90.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 3.55e-9

Gene Damage Prediction

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