TMEM219

protein-coding

transmembrane protein 219

Gene summary

Predicted to be involved in several processes, including ERK1 and ERK2 cascade; positive regulation of ERK1 and ERK2 cascade; and transforming growth factor beta1 production. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001083613.2

Inheritance

—

ClinVar variants

U:36B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr16:29,940,885-29,973,050

External References & Databases

Ensembl (ENSG00000149932)

Transcript & Mutation Effects

hg38 • Region Span ~32.2 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 TMEM219 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001083613.2. 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			1 clinvar		1 clinvar	2
missense			32 clinvar	1 clinvar	1 clinvar	34
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	36	1	2	39

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001083613.2	RefSeq	NP_001077082.1	4	MANE Select
ENST00000279396.11	Ensembl	ENSP00000279396.6	4	MANE Select
NM_001369688.1	RefSeq	NP_001356617.1	4	Standard
NM_001369689.1	RefSeq	NP_001356618.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
Generic Transcription Pathway
TP53 Regulates Transcription of Cell Death Genes
RNA Polymerase II Transcription
Transcriptional Regulation by TP53

Biological Process

apoptotic process
regulation of apoptotic process

Molecular Function

protein binding

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000566848
Coding exons: 4
Length: 32168
Individuals with no LoFs: 124772
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 124797
p: 0.000100

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.242	126	134	0.941	0.00000723	1516
Missense (PolyPhen)		43	44.603	0.96407		533
Synonymous	0.441	53	57.2	0.926	0.00000293	554
Loss of Function	0.579	7	8.86	0.790	4.61e-7	96

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00026	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell death receptor specific for IGFBP3, may mediate caspase-8-dependent apoptosis upon ligand binding. {ECO:0000269|PubMed:20353938}.;

Intolerance Scores

LoFtool: 0.322
RVIS EVS: -0.21
RVIS percentile EVS: 38.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.120

Gene Damage Prediction

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