TMEM25

protein-coding

transmembrane protein 25, the group of C2-set domain containing

Gene summary

Predicted to be involved in negative regulation of excitatory postsynaptic potential and regulation of protein stability. Predicted to be located in late endosome and lysosome. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_032780.4

Inheritance

—

ClinVar variants

U:77B:1

Top phenotype

Autism

gnomAD constraint

pLI —, LoF o/e 1.03

Max pathogenic AF

—

Genomic locus

chr11:118,531,041-118,547,280

External References & Databases

Ensembl (ENSG00000149582)

Transcript & Mutation Effects

hg38 • Region Span ~16.2 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 TMEM25 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 2

AutismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032780.4. 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			3 clinvar			3
missense			73 clinvar	1 clinvar		74
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	77	1	0	78

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 121 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032780.4	RefSeq	NP_116169.2	8	MANE Select
ENST00000313236.10	Ensembl	ENSP00000315635.5	8	MANE Select
NM_001144034.2	RefSeq	NP_001137506.1	7	Standard
NM_001144035.2	RefSeq	NP_001137507.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

extracellular region
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313236
Coding exons: 8
Length: 16240
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 57
Defined: 125748
p: 0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.311	215	228	0.942	0.0000141	2312
Missense (PolyPhen)		68	70.325	0.96695		799
Synonymous	0.408	95	100	0.948	0.00000612	827
Loss of Function	-0.112	16	15.5	1.03	7.47e-7	166

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00071	0.00071	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00042	0.00042	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.940
RVIS EVS: 0.2
RVIS percentile EVS: 67.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.680

Gene Damage Prediction

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